1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine [MDMA] by Asch

Query Query O

Results

Date

52 substances in Reaxys

2016-08-22 13h:27m:51s (EST)

H N

1. Query O

Search as: As drawn

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Reaxys ID 7875113 View in Reaxys

H 11 3 C

H N

1/52 Linear Structure Formula: C10 (11)CH15NO2 Molecular Formula: C11H15NO2 Molecular Weight: 192.235 Type of Substance: heterocyclic InChI Key: SHXWCVYOXRDMCX-JVVVGQRLSA-N Note:

O O

Reaxys ID 158675 View in Reaxys

H N

2/52 CAS Registry Number: 42542-10-9 Chemical Name: 3,4-methylenedioxymethamphetamine Linear Structure Formula: C11H15O2N Molecular Formula: C11H15NO2 Molecular Weight: 193.246 Type of Substance: heterocyclic InChI Key: SHXWCVYOXRDMCX-UHFFFAOYSA-N Note:

O O

Substance Label (17) Label References MDMA

Frison, G.; Castagna, F.; Brusini, G.; Tedeschi, L.; Seraglia, R.; Traldi, P.; Organic Mass Spectrometry; vol. 27; nb. 11; (1992); p. 1284 - 1288, View in Reaxys; Fitzgerald; Reid; Journal of Pharmacy and Pharmacology; vol. 46; nb. 10; (1994); p. 826 - 832, View in Reaxys; Kaufman, Melvin S.; Hatzis, Alexander C.; Stuart, John G.; Journal of Mass Spectrometry; vol. 31; nb. 8; (1996); p. 913 - 920, View in Reaxys; Colado, Maria Isabel; Green, A. Richard; European Journal of Pharmacology; vol. 280; nb. 3; (1995); p. 343 - 346, View in Reaxys; Walubo; Seger; Human and Experimental Toxicology; vol. 18; nb. 2; (1999); p. 119 - 125, View in Reaxys; Cirimele; Kintz; Mangin; Archives of Toxicology; vol. 70; nb. 1; (1995); p. 68 - 69, View in Reaxys; Zheng, Yiwen; Russell, Bruce; Schmierer, David; Laverty, Richard; Journal of Pharmacy and Pharmacology; vol. 49; nb. 1; (1997); p. 89 - 96, View in Reaxys; Nakahara, Yuji; Kikura, Ruri; Archives of Toxicology; vol. 70; nb. 12; (1996); p. 841 - 849, View in Reaxys; Nakahara; Takahashi; Kikura; Biological and Pharmaceutical Bulletin; vol. 18; nb. 9; (1995); p. 1223 - 1227, View in Reaxys; Schmidt; Sorensen; Kehne; Carr; Palfreyman; Life Sciences; vol. 56; nb. 25; (1995); p. 2209 - 2222, View in Reaxys; Walker; Davenport-Jones; Fox; Atterwill; Cell Biology and Toxicology; vol. 15; nb. 3; (1999); p. 137 - 142, View in Reaxys; Sprague; Nichols; Journal of Pharmacology and Experimental Therapeutics; vol. 273; nb. 2; (1995); p. 667 - 673, View in Reaxys; Segura; Ortuno; Farre; Mc Lure; Pujadas; Pizarro; Llebaria; Joglar; Roset; De la Torre; Chemical Research in Toxicology; vol. 14; nb. 9; (2001); p. 1203 - 1208, View in Reaxys; Colado, Maria Isabel; Granados, Raquel; O'Shea, Esther; Esteban, Blanca; Green, A. Richard; Pharmacology and Toxicology; vol. 84; nb. 6; (1999); p. 261 - 266, View in Reaxys; Gartside; McQuade; Sharp; Journal of Pharmacology and Experimental Therapeutics; vol. 279; nb. 1; (1996); p. 277 283, View in Reaxys; Carter, James F.; Titterton, Emma L.; Grant, Helen; Sleeman, Richard; Chemical Communications; nb. 21; (2002); p. 2590 - 2591, View in Reaxys; Carvalho, Marcia; Carvalho, Felix; Remiao, Fernando; De Lourdes Pereira, Maria; Pires-Das-Neves, Ricardo; De Lourdes Bastos, Maria; Archives of Toxicology; vol. 76; nb. 3; (2002); p. 166 - 172, View in Reaxys; Gesi, Marco; Soldani, Paola; Lenzi, Paola; Ferrucci, Michela; Giusiani, Alberto; Fornai, Francesco; Paparelli, Antonio; Pharmacology and toxicology; vol. 91; nb. 1; (2002); p. 29 - 33, View in Reaxys; Pubill, David; Canudas, Anna M.; Pallas, Merce; Camins, Antonio; Camarasa, Jorge; Escubedo, Elena; Naunyn-Schmiedeberg's Archives of Pharmacology; vol. 367; nb. 5; (2003); p. 490 - 499, View in Reaxys; Pihlainen, Katja; Grigoras, Kestutis; Franssila, Sami; Ketola, Raimo; Kotiaho, Tapio; Kostiainen, Risto; Journal of Mass Spectrometry; vol. 40; nb. 4; (2005); p. 539 - 545, View in Reaxys; Darvesh, Altaf S.; Yamamoto, Bryan K.; Gudelsky, Gary A.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 2; (2005); p. 694 - 701, View in Reaxys; Pichini, Simona; Pacifici, Roberta; Pellegrini, Manuela; Marchei, Emilia; Lozano, Jaime; Murillo, Janeth; Vall, Oriol; Garcia-Algar, Oscar; Analytical Chemistry; vol. 76; nb. 7; (2004); p. 2124 - 2132, View in Reaxys; Sanchez; Camarero; Esteban; Peter; Green; Colado; British Journal of Pharmacology; vol. 134; nb. 1; (2001); p. 46 - 57, View in Reaxys; Castiglioni, Sara; Zuccato, Ettore; Crisci, Elisabetta; Chiabrando, Chiara; Fanelli, Roberte; Bagnati, Renzo; Analytical Chemistry; vol. 78; nb. 24; (2006); p. 8421 - 8429, View in Reaxys; Postigo, Cristina; Lopez De Alda, Maria J.; Barcelo, Damia; Analytical Chemistry; vol. 80; nb. 9; (2008); p. 3123 - 3134, View in Reaxys; Buchanan, Hilary A. S.; Daeid, Niamh Nic; Meier-Augenstein, Wolfram; Kemp, Helen F.; Kerr, William J.; Middleditch, Michael; Analytical Chemistry; vol. 80; nb. 9; (2008); p. 3350 - 3356, View in Reaxys; Montesano, Camilla; Sergi, Manuel; Moro, Mariaelena; Napoletano, Sabino; Romolo, Francesco Saverio; Carlo, Michele Del; Compagnone, Dario; Curini, Roberta; Journal of Mass Spectrometry; vol. 48; nb. 1; (2013); p. 49 - 59, View in Reaxys; Concheiro, Marta; Baumann, Michael H.; Scheidweiler, Karl B.; Rothman, Richard B.; Marrone, Gina F.; Huestis, Marilyn A.; Drug Metabolism and Disposition; vol. 42; nb. 1; (2014); p. 119 - 125, View in Reaxys

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rac-MDMA

Pifl, Christian; Nagy, Gabor; Berenyi, Sandor; Kattinger, Alexandra; Reither, Harald; Antus, Sandor; Journal of Pharmacology and Experimental Therapeutics; vol. 314; nb. 1; (2005); p. 346 - 354, View in Reaxys

R/S-MDMA

Keizers, Peter H. J.; De Graaf, Chris; De Kanter, Frans J. J.; Oostenbrink, Chris; Feenstra, K. Anton; Commandeur, Jan N. M.; Vermeulen, Nico P. E.; Journal of Medicinal Chemistry; vol. 48; nb. 19; (2005); p. 6117 - 6127, View in Reaxys

Fig. 1., Negwer8 2882

Jones, Douglas C.; Lau, Serrine S.; Monks, Terrence J.; Journal of Pharmacology and Experimental Therapeutics; vol. 311; nb. 1; (2004); p. 298 - 306, View in Reaxys

Negwer8 2882

Robledo, Patricia; Balerio, Graciela; Berrendero, Fernando; Maldonado, Rafael; Naunyn-Schmiedeberg's Archives of Pharmacology; vol. 369; nb. 3; (2004); p. 338 - 349, View in Reaxys

Merck12 5806; MDMA

Hernandez-Lopez, Candido; Farre, Magi; Roset, Pere N.; Menoyo, Esther; Pizarro, Nieves; Ortuno, Jordi; Torrens, Marta; Cami, Jordi; De La Torre, Rafael; Journal of Pharmacology and Experimental Therapeutics; vol. 300; nb. 1; (2002); p. 236 - 244, View in Reaxys

DL-MDMA

McCooeye, Margaret A.; Mester, Zoltan; Ells, Barbara; Barnett, David A.; Purves, Randy W.; Guevremont, Roger; Analytical Chemistry; vol. 74; nb. 13; (2002); p. 3071 - 3075, View in Reaxys

I; MDMA

Bai; Jones; Lau; Monks; Chemical Research in Toxicology; vol. 14; nb. 7; (2001); p. 863 - 870, View in Reaxys

MDMA, Merck 5806

Ratzenboeck, Elisabeth; Saria, Alois; Kriechbaum, Norbert; Zernig, Gerald; Pharmacology; vol. 62; nb. 3; (2001); p. 138 - 144, View in Reaxys

Merck 5806

Pacifici, Roberta; Zuccaro, Piergiorgio; Hernandez Lopez, Candido; Pichini, Simona; Di Carlo, Simonetta; Farre, Magi; Roset, Pere Nolasc; Ortuno, Jordi; Segura, Jordi; De La Torre, Rafael; Journal of Pharmacology and Experimental Therapeutics; vol. 296; nb. 1; (2001); p. 207 - 215, View in Reaxys

2b, MDMA

Borth, Swantje; Haensel, Wolfram; Roesner, Peter; Junge, Thomas; Journal of Mass Spectrometry; vol. 35; nb. 6; (2000); p. 705 - 710, View in Reaxys

(+/-)MDMA

Chu, Teresa; Kumagai, Yoshito; DiStefano, Emma W.; Cho, Arthur K.; Biochemical Pharmacology; vol. 51; nb. 6; (1996); p. 789 - 796, View in Reaxys

1 (MDMA)

Johnson; Frescas; Oberlender; Nichols; Journal of Medicinal Chemistry; vol. 34; nb. 5; (1991); p. 1662 1668, View in Reaxys

IIB, MDMA

Braun; Shulgin; Arzneimittel-Forschung; vol. 30; nb. 5; (1980); p. 825 - 830, View in Reaxys

IIb

Braun; Shulgin; Journal of Pharmaceutical Sciences; vol. 69; nb. 2; (1980); p. 192 - 195, View in Reaxys

Patent-Specific Data (3) Prophetic ComLocation in Patent References pound Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys prophetic product

Patent; Caron, Marc G.; Sotnikova, Tatyana D.; Gainetdinov, Raul R.; US2007/27208; (2007); (A1) English, View in Reaxys Claim

Derivative (2) Comment (Derivative) Hydrochlorid: aus ethanol. Loesg. des Amins mit ethanol. HCl; F: 148-149grad

Patent; Owens, Samuel M.; Carroll, Frank Ivy; Abraham, Philip; US2003/119083; (2003); (A1) English, View in Reaxys; Patent; McConnell, Robert Ivan; Benchikh, Elouard; Fitzgerald, Stephen Peter; Lamont, John Victor; US2004/121400; (2004); (A1) English, View in Reaxys; Patent; Ekins, Sean; US2002/13372; (2002); (A1) English, View in Reaxys; Patent; Owens, Samuel M.; Carroll, Frank Ivy; Abraham, Philip; US2001/51158; (2001); (A1) English, View in Reaxys

References Biniecki; Krajewski; Acta Poloniae Pharmaceutica; vol. 17; (1960); p. 421,422, 423; Chem.Abstr.; vol. 55; nb. 14350; (1961), View in Reaxys

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Hydrochlorid: aus. Biniecki; Krajewski; Acta Poloniae Pharmaceutica; vol. 17; (1960); p. 421,422, 423; Chem.Abstr.; vol. 55; d. Amin u. HCl in nb. 14350; (1961), View in Reaxys A.; F.: 148-149grad Boiling Point (2) Boiling Point [°C]

Pressure (Boiling Point) [Torr]

130 - 180

155

Comment (Boiling References Point) Biniecki; Krajewski; Acta Poloniae Pharmaceutica; vol. 17; (1960); p. 421,422, 423; Chem.Abstr.; vol. 55; nb. 14350; (1961), View in Reaxys Oel.

Patent; Merck; DE274350; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 12; p. 768, View in Reaxys

Refractive Index (1) Refractive Index Wavelength (Refractive Index) [nm]

Temperature (Refractive Index) [°C]

References

1.5311

Biniecki; Krajewski; Acta Poloniae Pharmaceutica; vol. 17; (1960); p. 421,422, 423; Chem.Abstr.; vol. 55; nb. 14350; (1961), View in Reaxys

589

Association (MCS) (1) 1 of 1

Description (Association Stability constant of the complex with ... (MCS)) Solvent (Association (MCS))

dimethylsulfoxide; aq. phosphate buffer

Temperature (Association (MCS)) [°C]

Partner (Association (MCS))

melanin

Nakahara; Takahashi; Kikura; Biological and Pharmaceutical Bulletin; vol. 18; nb. 9; (1995); p. 1223 - 1227, View in Reaxys Chromatographic Data (3) Chromatographic References data LC (Liquid chromatography)

Fedorova, Ganna; Randak, Tomas; Lindberg, Richard H.; Grabic, Roman; Rapid Communications in Mass Spectrometry; vol. 27; nb. 15; (2013); p. 1751 - 1762, View in Reaxys; Spinner; Klima; Kempf; Huppertz; Auwärter; Altenburger; Neukamm; Journal of Mass Spectrometry; vol. 49; nb. 12; (2014); p. 1306 1313, View in Reaxys; Jeong, Eun Sook; Kim, So-Hee; Cha, Eun-Ju; Lee, Kang Mi; Kim, Ho Jun; Lee, Sang-Won; Kwon, Oh-Seung; Lee, Jaeick; Rapid Communications in Mass Spectrometry; vol. 29; nb. 4; (2015); p. 367 - 384, View in Reaxys; Jeong, Eun Sook; Kim, So-Hee; Cha, Eun-Ju; Lee, Kang Mi; Kim, Ho Jun; Lee, Sang-Won; Kwon, Oh-Seung; Lee, Jaeick; Rapid Communications in Mass Spectrometry; vol. 29; nb. 4; (2015); p. 367 - 384, View in Reaxys

UPLC (Ultra performance liquid chromatography)

Lin, Huei-Ru; Liao, Chao-Chuan; Lin, Tzu-Chieh; Rapid Communications in Mass Spectrometry; vol. 28; nb. 19; (2014); p. 2043 - 2053, View in Reaxys

HPLC (High performance liquid chromatography)

Montesano, Camilla; Sergi, Manuel; Moro, Mariaelena; Napoletano, Sabino; Romolo, Francesco Saverio; Carlo, Michele Del; Compagnone, Dario; Curini, Roberta; Journal of Mass Spectrometry; vol. 48; nb. 1; (2013); p. 49 - 59, View in Reaxys

Crystal Property Description (2) Colour & Other References Properties deep-yellow

Buchanan, Hilary A. S.; Daeid, Niamh Nic; Meier-Augenstein, Wolfram; Kemp, Helen F.; Kerr, William J.; Middleditch, Michael; Analytical Chemistry; vol. 80; nb. 9; (2008); p. 3350 - 3356, View in Reaxys Biniecki; Krajewski; Acta Poloniae Pharmaceutica; vol. 17; (1960); p. 421,422, 423; Chem.Abstr.; vol. 55; nb. 14350; (1961), View in Reaxys

Liquid/Liquid Systems (MCS) (1) 1 of 1

Description (Liquid/ Liquid Systems (MCS))

Distribution between solvent 1 + 2

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Comment (Liquid/Liquid Systems (MCS))

ambient temperature

Partner (Liquid/Liquid Systems (MCS))

octanol

Nakahara, Yuji; Hanajiri, Ruri; Life Sciences; vol. 66; nb. 7; (2000); p. 563 - 574, View in Reaxys NMR Spectroscopy (5) 1 of 5

Description (NMR Spec- Chemical shifts troscopy) Nucleus (NMR Spectroscopy)

Solvents (NMR Spectro- chloroform-d1 scopy) Frequency (NMR Spectroscopy) [MHz]

300

Schulze, Matthias; Synthetic Communications; vol. 40; nb. 10; (2010); p. 1461 - 1476, View in Reaxys 2 of 5

Description (NMR Spec- Chemical shifts troscopy) Nucleus (NMR Spectroscopy)

13C

Solvents (NMR Spectro- chloroform-d1 scopy) Frequency (NMR Spectroscopy) [MHz]

Schulze, Matthias; Synthetic Communications; vol. 40; nb. 10; (2010); p. 1461 - 1476, View in Reaxys 3 of 5

Description (NMR Spec- Chemical shifts troscopy) Nucleus (NMR Spectroscopy)

Solvents (NMR Spectro- CDCl3 scopy) Frequency (NMR Spectroscopy) [MHz]

400

Description (NMR Spec- Chemical shifts troscopy) Nucleus (NMR Spectroscopy)

13C

Solvents (NMR Spectro- CDCl3 scopy) Frequency (NMR Spectroscopy) [MHz]

100

Description (NMR Spec- Chemical shifts troscopy) Nucleus (NMR Spectroscopy)

13C

Carter, James F.; Titterton, Emma L.; Grant, Helen; Sleeman, Richard; Chemical Communications; nb. 21; (2002); p. 2590 - 2591, View in Reaxys IR Spectroscopy (1)

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1 of 1

Description (IR Spectroscopy)

Bands

Solvent (IR Spectroscopy)

CH2Cl2

Buchanan, Hilary A. S.; Daeid, Niamh Nic; Meier-Augenstein, Wolfram; Kemp, Helen F.; Kerr, William J.; Middleditch, Michael; Analytical Chemistry; vol. 80; nb. 9; (2008); p. 3350 - 3356, View in Reaxys Mass Spectrometry (23) Description (Mass Comment (Mass Spectrometry) Spectrometry)

References

high resolution mass spectrometry (HRMS); spectrum

Duvivier, Wilco F.; Van Putten, Marc R.; Van Beek, Teris A.; Nielen, Michel W. F.; Analytical Chemistry; vol. 88; nb. 4; (2016); p. 2489 - 2496, View in Reaxys

electrospray ionisation (ESI); spectrum

Huang, Min-Zong; Zhou, Chi-Chang; Liu, De-Lin; Jhang, Siou-Sian; Cheng, SyChyi; Shiea, Jentaie; Analytical Chemistry; vol. 85; nb. 19; (2013); p. 8956 - 8963, View in Reaxys; Stojanovska, Natasha; Kelly, Tamsin; Tahtouh, Mark; Beavis, Alison; Fu, Shanlin; Rapid Communications in Mass Spectrometry; vol. 28; nb. 7; (2014); p. 731 - 740, View in Reaxys; Jeong, Eun Sook; Kim, So-Hee; Cha, Eun-Ju; Lee, Kang Mi; Kim, Ho Jun; Lee, Sang-Won; Kwon, Oh-Seung; Lee, Jaeick; Rapid Communications in Mass Spectrometry; vol. 29; nb. 4; (2015); p. 367 - 384, View in Reaxys

liquid chromatography mass spectrometry (LCMS); electrospray ionisation (ESI); spectrum

Jeong, Eun Sook; Kim, So-Hee; Cha, Eun-Ju; Lee, Kang Mi; Kim, Ho Jun; Lee, Sang-Won; Kwon, Oh-Seung; Lee, Jaeick; Rapid Communications in Mass Spectrometry; vol. 29; nb. 4; (2015); p. 367 - 384, View in Reaxys

spectrum

McCooeye, Margaret A.; Mester, Zoltan; Ells, Barbara; Barnett, David A.; Purves, Randy W.; Guevremont, Roger; Analytical Chemistry; vol. 74; nb. 13; (2002); p. 3071 3075, View in Reaxys; Jones-Lepp; Alvarez; Petty; Huckins; Archives of Environmental Contamination and Toxicology; vol. 47; nb. 4; (2004); p. 427 - 439, View in Reaxys; Schaper, J. Niklas; Pfeuffer, Kevin P.; Shelley, Jacob T.; Bings, Nicolas H.; Hieftje, Gary M.; Analytical Chemistry; vol. 84; nb. 21; (2012); p. 9246 - 9252, View in Reaxys; Espy, Ryan D.; Teunissen, Sebastiaan Frans; Manicke, Nicholas E.; Ren, Yue; Ouyang, Zheng; Van Asten, Arian; Cooks, R. Graham; Analytical Chemistry; vol. 86; nb. 15; (2014); p. 7712 - 7718, View in Reaxys

tandem mass spectrometry; fragmentation pattern; spectrum

Stojanovska, Natasha; Kelly, Tamsin; Tahtouh, Mark; Beavis, Alison; Fu, Shanlin; Rapid Communications in Mass Spectrometry; vol. 28; nb. 7; (2014); p. 731 - 740, View in Reaxys

tandem mass spectrometry; spectrum

Hendricks, Paul I.; Dalgleish, Jon K.; Shelley, Jacob T.; Kirleis, Matthew A.; McNicholas, Matthew T.; Li, Linfan; Chen, Tsung-Chi; Chen, Chien-Hsun; Duncan, Jason S.; Boudreau, Frank; Noll, Robert J.; Denton, John P.; Roach, Timothy A.; Ouyang, Zheng; Cooks, R. Graham; Analytical Chemistry; vol. 86; nb. 6; (2014); p. 2900 - 2908, View in Reaxys

liquid chromatography mass spectrometry (LCMS); CID (collision-induced dissociation); spectrum

Lin, Huei-Ru; Liao, Chao-Chuan; Lin, Tzu-Chieh; Rapid Communications in Mass Spectrometry; vol. 28; nb. 19; (2014); p. 2043 - 2053, View in Reaxys

high resolution mass spectrometry (HRMS); liquid chromatography mass spectrometry (LCMS); timeof-flight mass spectra (TOFMS); tandem mass spectrometry; spectrum

Roemmelt, Andreas T.; Steuer, Andrea E.; Poetzsch, Michael; Kraemer, Thomas; Analytical Chemistry; vol. 86; nb. 23; (2014); p. 11742 - 11749, View in Reaxys

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liquid chromatography mass spectrometry (LCMS); electrospray ionisation (ESI); tandem mass spectrometry; spectrum

Spinner; Klima; Kempf; Huppertz; Auwärter; Altenburger; Neukamm; Journal of Mass Spectrometry; vol. 49; nb. 12; (2014); p. 1306 - 1313, View in Reaxys

liquid chromatography mass spectrometry (LCMS); tandem mass spectrometry; spectrum

tandem mass spectrometry; electrospray ionisation (ESI); high resolution mass spectrometry (HRMS); spectrum

Fedorova, Ganna; Randak, Tomas; Lindberg, Richard H.; Grabic, Roman; Rapid Communications in Mass Spectrometry; vol. 27; nb. 15; (2013); p. 1751 - 1762, View in Reaxys

electrospray ionisation (ESI); high resolution mass spectrometry (HRMS); spectrum

Fedorova, Ganna; Randak, Tomas; Lindberg, Richard H.; Grabic, Roman; Rapid Communications in Mass Spectrometry; vol. 27; nb. 15; (2013); p. 1751 - 1762, View in Reaxys

IT (ion trap); electrospray ionisation (ESI); tandem mass spectrometry; CID (collisioninduced dissociation); fragmentation pattern; spectrum

Vircks, Kyle E.; Mulligan, Christopher C.; Rapid Communications in Mass Spectrometry; vol. 26; nb. 23; (2012); p. 2665 - 2672, View in Reaxys

TOFMS (Time of flight mass spectrum); ESI (Electrospray ionisation); Spectrum

Bijlsma, Lubertus; Sancho, Juan V.; Hernandez, Felix; Niessen, Wilfried M.A.; Journal of Mass Spectrometry; vol. 46; nb. 9; (2011); p. 865 - 875, View in Reaxys

HRMS (High resolution mass spectrometry); TOFMS (Time of flight mass spectrum); ESI (Electrospray ionisation); LCMS (Liquid chromatography mass spectrometry); Spectrum

Vonaparti; Lyris; Angelis; Panderi; Koupparis; Tsantili-Kakoulidou; Peters; Nielen; Georgakopoulos; Rapid Communications in Mass Spectrometry; vol. 24; nb. 11; (2010); p. 1595 - 1609, View in Reaxys

APCI (atmospheric pressure chemical ionization); Spectrum

Inoue, Hiroyuki; Hashimoto, Hiroaki; Watanabe, Susumu; Iwata, Yuko T.; Kanamori, Tatsuyuki; Miyaguchi, Hajime; Tsujikawa, Kenji; Kuwayama, Kenji; Tachi, Noriyuki; Uetake, Naohito; Journal of Mass Spectrometry; vol. 44; nb. 9; (2009); p. 1300 - 1307, View in Reaxys

APCI (atmospheric pressure chemical ionization); Tandem mass spectrometry; Spectrum

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LCMS (Liquid chromatography mass spectrometry); ESI (Electrospray ionisation); Tandem mass spectrometry; Spectrum

mol peak

Thoerngren, John-Olof; Oestervall, Fredrik; Garle, Mats; Journal of Mass Spectrometry; vol. 43; nb. 7; (2008); p. 980 - 992, View in Reaxys

spectrum; collision-induced dissociation

Castiglioni, Sara; Zuccato, Ettore; Crisci, Elisabetta; Chiabrando, Chiara; Fanelli, Roberte; Bagnati, Renzo; Analytical Chemistry; vol. 78; nb. 24; (2006); p. 8421 - 8429, View in Reaxys

spectrum; tandem mass spectrometry

Pihlainen, Katja; Grigoras, Kestutis; Franssila, Sami; Ketola, Raimo; Kotiaho, Tapio; Kostiainen, Risto; Journal of Mass Spectrometry; vol. 40; nb. 4; (2005); p. 539 545, View in Reaxys

collision-induced dissociation; spectrum

Jones-Lepp; Alvarez; Petty; Huckins; Archives of Environmental Contamination and Toxicology; vol. 47; nb. 4; (2004); p. 427 - 439, View in Reaxys

spectrum; collision-induced dissociation; tandem mass spectrometry

Borth, Swantje; Haensel, Wolfram; Roesner, Peter; Junge, Thomas; Journal of Mass Spectrometry; vol. 35; nb. 6; (2000); p. 705 - 710, View in Reaxys

chemical ionization (CI); electron impact (EI)

Borth, Swantje; Haensel, Wolfram; Roesner, Peter; Junge, Thomas; Journal of Mass Spectrometry; vol. 35; nb. 6; (2000); p. 705 - 710, View in Reaxys

Raman Spectroscopy (1) Description (Ram- References an Spectroscopy) Raman

West, Matthew J.; Went, Michael J.; Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy; vol. 71; nb. 5; (2009); p. 1984 - 1988, View in Reaxys

Pharmacological Data (373) 1 of 373

Comment (Pharmacological Data)

Bioactivities present

Patent; Owens, Samuel M.; Carroll, Frank Ivy; Abraham, Philip; US2003/119083; (2003); (A1) English, View in Reaxys; Patent; THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE DEPARTMENT OF HEALTH AND HUMAN SERVICES; WO1993/8281; (1993); (A1), View in Reaxys; Patent; McConnell, Robert Ivan; Benchikh, Elouard; Fitzgerald, Stephen Peter; Lamont, John Victor; US2004/121400; (2004); (A1) English, View in Reaxys; Patent; VANDERBILT UNIVERSITY; WO2005/7856; (2005); (A1) english, View in Reaxys; Patent; MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH; WO2005/107473; (2005); (A2) English, View in Reaxys; Patent; Ghosal, Shibnath; US2005/282781; (2005); (A1) English, View in Reaxys; Patent; BAYLOR COLLEGE OF MEDICINE; US2006/18921; (2006); (A1) English, View in Reaxys; Patent; ABBOTT GMBH and CO.KG; WO2006/40177; (2006); (A1) English, View in Reaxys; Patent; Centre National de la Recherche Scientifique - CNRS, an organization of France; US2006/116341; (2006); (A1) English, View in Reaxys; Patent; Caron, Marc G.; Sotnikova, Tatyana D.; Gainetdinov, Raul R.; US2007/27208; (2007); (A1) English, View in Reaxys; Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys; Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys; Patent; Merck; DE274350; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 12; p. 768, View in Reaxys; Patent; Merck; DE334555; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 13; p. 885, View in Reaxys; Patent; Rosenmund; DE336153; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 13; p. 885, View in Reaxys; Biniecki; Krajewski; Acta Poloniae Pharmaceutica; vol. 17; (1960); p. 421,422, 423; Chem.Abstr.; vol. 55; nb. 14350; (1961), View in Reaxys; Johnson; Frescas; Oberlender; Nichols; Journal of Medicinal Chemistry; vol. 34; nb. 5; (1991); p. 1662 - 1668, View in Reaxys; Frison, G.; Castagna, F.; Brusini, G.; Tedeschi, L.; Seraglia, R.; Traldi, P.; Organic Mass Spectrometry; vol. 27; nb. 11; (1992); p. 1284 - 1288, View in Reaxys; Braun; Shulgin; Arzneimittel-Forschung; vol. 30; nb. 5; (1980); p. 825 - 830, View in Reaxys; Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015, View in Reaxys 2 of 373

Comment (Pharmacological Data)

Bioactivities present

Braun; Shulgin; Journal of Pharmaceutical Sciences; vol. 69; nb. 2; (1980); p. 192 - 195, View in Reaxys; Fitzgerald; Reid; Journal of Pharmacy and Pharmacology; vol. 46; nb. 10; (1994); p. 826 - 832, View in Reaxys; Kaufman, Melvin S.; Hatzis, Alexander C.; Stuart, John G.; Journal of Mass Spectrometry; vol. 31; nb. 8; (1996); p. 913 920, View in Reaxys; Colado, Maria Isabel; Green, A. Richard; European Journal of Pharmacology; vol. 280; nb. 3; (1995); p. 343 - 346, View in Reaxys; Walubo; Seger; Human and Experimental Toxicology; vol. 18; nb. 2; (1999); p. 119 - 125, View in Reaxys; Cirimele; Kintz; Mangin; Archives of Toxicology; vol. 70; nb. 1; (1995); p. 68 -

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69, View in Reaxys; Zheng, Yiwen; Russell, Bruce; Schmierer, David; Laverty, Richard; Journal of Pharmacy and Pharmacology; vol. 49; nb. 1; (1997); p. 89 - 96, View in Reaxys; Nakahara, Yuji; Kikura, Ruri; Archives of Toxicology; vol. 70; nb. 12; (1996); p. 841 - 849, View in Reaxys; Nakahara; Takahashi; Kikura; Biological and Pharmaceutical Bulletin; vol. 18; nb. 9; (1995); p. 1223 - 1227, View in Reaxys; Schmidt; Sorensen; Kehne; Carr; Palfreyman; Life Sciences; vol. 56; nb. 25; (1995); p. 2209 - 2222, View in Reaxys; Nakahara, Yuji; Kikura, Ruri; Biological and Pharmaceutical Bulletin; vol. 20; nb. 9; (1997); p. 969 - 972, View in Reaxys; Tirelli; Witkin; Journal of Pharmacology and Experimental Therapeutics; vol. 273; nb. 1; (1995); p. 7 - 16, View in Reaxys; Premkumar; Ahern; Journal of Pharmacology and Experimental Therapeutics; vol. 274; nb. 2; (1995); p. 718 - 722, View in Reaxys; Walker; Davenport-Jones; Fox; Atterwill; Cell Biology and Toxicology; vol. 15; nb. 3; (1999); p. 137 - 142, View in Reaxys; Sprague; Nichols; Journal of Pharmacology and Experimental Therapeutics; vol. 273; nb. 2; (1995); p. 667 - 673, View in Reaxys; Borth, Swantje; Haensel, Wolfram; Roesner, Peter; Junge, Thomas; Journal of Mass Spectrometry; vol. 35; nb. 6; (2000); p. 705 - 710, View in Reaxys; Venhorst, Jennifer; Onderwater, Rob C.A.; Meerman, John H.N.; Vermeulen, Nico P.E.; Commandeur, Jan N.M.; European Journal of Pharmaceutical Sciences; vol. 12; nb. 2; (2000); p. 151 - 158, View in Reaxys; Segura; Ortuno; Farre; Mc Lure; Pujadas; Pizarro; Llebaria; Joglar; Roset; De la Torre; Chemical Research in Toxicology; vol. 14; nb. 9; (2001); p. 1203 - 1208, View in Reaxys; Bai; Jones; Lau; Monks; Chemical Research in Toxicology; vol. 14; nb. 7; (2001); p. 863 - 870, View in Reaxys; Ratzenboeck, Elisabeth; Saria, Alois; Kriechbaum, Norbert; Zernig, Gerald; Pharmacology; vol. 62; nb. 3; (2001); p. 138 - 144, View in Reaxys 3 of 373

Comment (Pharmacological Data)

Bioactivities present

Chu, Teresa; Kumagai, Yoshito; DiStefano, Emma W.; Cho, Arthur K.; Biochemical Pharmacology; vol. 51; nb. 6; (1996); p. 789 - 796, View in Reaxys; Colado, Maria Isabel; Granados, Raquel; O'Shea, Esther; Esteban, Blanca; Green, A. Richard; Pharmacology and Toxicology; vol. 84; nb. 6; (1999); p. 261 - 266, View in Reaxys; Gartside; McQuade; Sharp; Journal of Pharmacology and Experimental Therapeutics; vol. 279; nb. 1; (1996); p. 277 - 283, View in Reaxys; Carter, James F.; Titterton, Emma L.; Grant, Helen; Sleeman, Richard; Chemical Communications; nb. 21; (2002); p. 2590 - 2591, View in Reaxys; Carvalho, Marcia; Carvalho, Felix; Remiao, Fernando; De Lourdes Pereira, Maria; Pires-Das-Neves, Ricardo; De Lourdes Bastos, Maria; Archives of Toxicology; vol. 76; nb. 3; (2002); p. 166 - 172, View in Reaxys; Gesi, Marco; Soldani, Paola; Lenzi, Paola; Ferrucci, Michela; Giusiani, Alberto; Fornai, Francesco; Paparelli, Antonio; Pharmacology and toxicology; vol. 91; nb. 1; (2002); p. 29 - 33, View in Reaxys; McCooeye, Margaret A.; Mester, Zoltan; Ells, Barbara; Barnett, David A.; Purves, Randy W.; Guevremont, Roger; Analytical Chemistry; vol. 74; nb. 13; (2002); p. 3071 - 3075, View in Reaxys; Wu, Dafang; Victoria Otton, S.; Inaba, Tadanobu; Kalow, Werner; Sellers, Edward M.; Biochemical Pharmacology; vol. 53; nb. 11; (1997); p. 1605 - 1612, View in Reaxys; Hernandez-Lopez, Candido; Farre, Magi; Roset, Pere N.; Menoyo, Esther; Pizarro, Nieves; Ortuno, Jordi; Torrens, Marta; Cami, Jordi; De La Torre, Rafael; Journal of Pharmacology and Experimental Therapeutics; vol. 300; nb. 1; (2002); p. 236 - 244, View in Reaxys; Sprague, Jon E.; Banks, Matthew L.; Cook, Valerie J.; Mills, Edward M.; Journal of Pharmacology and Experimental Therapeutics; vol. 305; nb. 1; (2003); p. 159 - 166, View in Reaxys; Setola, Vincent; Hufeisen, Sandra J.; Grande-Allen, K. Jane; Vesely, Ivan; Glennon, Richard A.; Blough, Bruce; Rothman, Richard B.; Roth, Bryan L.; Molecular Pharmacology; vol. 63; nb. 6; (2003); p. 1223 - 1229, View in Reaxys; Pubill, David; Canudas, Anna M.; Pallas, Merce; Camins, Antonio; Camarasa, Jorge; Escubedo, Elena; Naunyn-Schmiedeberg's Archives of Pharmacology; vol. 367; nb. 5; (2003); p. 490 - 499, View in Reaxys; Scorza, Ma. Cecilia; Carrau, Cecilia; Silveira, Rodolfo; Zapata-Torres, Gerald; Cassels, Bruce K.; Reyes-Parada, Miguel; Biochemical Pharmacology; vol. 54; nb. 12; (1997); p. 1361 - 1369, View in Reaxys; De Souza; Kelly; Harkin; Leonard; Pharmacology and Toxicology; vol. 80; nb. 5; (1997); p. 207 - 210, View in Reaxys; Obach, R. Scott; Huynh, Phuong; Allen, Mary C.; Beedham, Christine; Journal of Clinical Pharmacology; vol. 44; nb. 1; (2004); p. 7 - 19, View in Reaxys; Keizers, Peter H.J.; Lussenburg, Barbara M.A.; De Graaf, Chris; Mentink, Letty M.; Vermeulen, Nico P.E.; Commandeur, Jan N.M.; Biochemical Pharmacology; vol. 68; nb. 11; (2004); p. 2263 - 2271, View in Reaxys; Montiel-Duarte, Cristina; Ansorena, Eduardo; Lopez-Zabalza, Maria Jesus; Cenarruzabeitia, Edurne; Iraburu, Maria J.; Biochemical Pharmacology; vol. 67; nb. 6; (2004); p. 1025 - 1033, View in Reaxys; Connor, Thomas J.; Harkin, Andrew; Kelly, John P.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 1; (2005); p. 134 - 143, View in Reaxys; Jones, Douglas C.; Duvauchelle, Christine; Ikegami, Aiko; Olsen, Christopher M.; Lau, Serrine S.; De La Torre, Rafael; Monks, Terrence J.; Journal of Pharmacology and Experimental Therapeutics; vol. 313; nb. 1; (2005); p. 422 - 431, View in Reaxys; Pihlainen, Katja; Grigoras, Kestutis; Franssila, Sami; Ketola, Raimo; Kotiaho, Tapio; Kostiainen, Risto; Journal of Mass Spectrometry; vol. 40; nb. 4; (2005); p. 539 - 545, View in Reaxys 4 of 373

Comment (Pharmacological Data)

Bioactivities present

Darvesh, Altaf S.; Yamamoto, Bryan K.; Gudelsky, Gary A.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 2; (2005); p. 694 - 701, View in Reaxys; Rusyniak, Daniel E.; Tandy, Stephany L.; Hekmatyar; Mills, Edward; Smith, David J.; Bansal, Navin; MacLellan, Darcy; Harper, Mary-Ellen; Sprague, Jon E.; Journal of Pharmacology and Experimental Therapeutics; vol. 313; nb. 2; (2005); p. 629 - 639, View in Reaxys; Pifl, Christian; Nagy, Gabor; Berenyi, Sandor; Kattinger, Alexandra; Reither, Harald; Antus, Sandor; Journal of Pharmacology and Experimental Therapeutics; vol. 314; nb. 1; (2005); p. 346 - 354, View in Reaxys; Jones, Douglas C.; Lau, Serrine S.; Monks, Terrence J.; Journal of Pharmacology and Experimental Therapeutics; vol. 311; nb. 1; (2004); p. 298 - 306, View in Reaxys; Wakonigg, Gudrun; Sturm, Katja; Saria, Alois; Zernig, Gerald; Pharmacology; vol. 69; nb. 4; (2003); p. 180 - 182, View in Reaxys; Pichini, Simona; Pacifici, Roberta; Pellegrini, Manuela; Marchei, Emilia; Lozano, Jaime; Murillo, Janeth; Vall, Oriol; Garcia-Algar, Oscar; Analytical Chemistry; vol. 76; nb. 7; (2004); p. 2124 - 2132, View in Reaxys; Keizers, Peter H. J.; De Graaf, Chris; De Kanter, Frans

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J. J.; Oostenbrink, Chris; Feenstra, K. Anton; Commandeur, Jan N. M.; Vermeulen, Nico P. E.; Journal of Medicinal Chemistry; vol. 48; nb. 19; (2005); p. 6117 - 6127, View in Reaxys; Jones-Lepp; Alvarez; Petty; Huckins; Archives of Environmental Contamination and Toxicology; vol. 47; nb. 4; (2004); p. 427 - 439, View in Reaxys; Robledo, Patricia; Balerio, Graciela; Berrendero, Fernando; Maldonado, Rafael; Naunyn-Schmiedeberg's Archives of Pharmacology; vol. 369; nb. 3; (2004); p. 338 - 349, View in Reaxys; Capela, Joao Paulo; Meisel, Andreas; Abreu, Artur Reis; Branco, Paula Serio; Ferreira, Luisa Maria; Lobo, Ana Maria; Remiao, Fernando; Bastos, Maria Lurdes; Carvalho, Felix; Journal of Pharmacology and Experimental Therapeutics; vol. 316; nb. 1; (2006); p. 53 - 61, View in Reaxys; Klingler, Werner; Heffron, James J. A.; Jurkat-Rott, Karin; O'Sullivan, Grainne; Alt, Andreas; Schlesinger, Friedrich; Bufler, Johannes; Lehmann-Horn, Frank; Journal of Pharmacology and Experimental Therapeutics; vol. 314; nb. 3; (2005); p. 1267 - 1273, View in Reaxys; Lussenburg, Barbara M.A.; Keizers, Peter H.J.; De Graaf, Chris; Hidestrand, Mats; Ingelman-Sundberg; Vermeulen, Nico P.E.; Commandeur, Jan N.M.; Biochemical Pharmacology; vol. 70; nb. 8; (2005); p. 1253 - 1261, View in Reaxys; Green, A. Richard; O'Shea, Esther; Saadat, Kathryn S.; Elliott, J. Martin; Colado, M. Isabel; British Journal of Pharmacology; vol. 146; nb. 2; (2005); p. 306 - 312, View in Reaxys; Bexis, Sotiria; Docherty, James R.; British Journal of Pharmacology; vol. 146; nb. 1; (2005); p. 1 - 6, View in Reaxys; De La Torre, Rafael; Farre, Magi; Mathuna, Brian O.; Roset, Pere N.; Pizarro, Neus; Segura, Mireia; Torrens, Marta; Ortuno, Jordi; Pujadas, Mitona; Cami, Jordi; European Journal of Clinical Pharmacology; vol. 61; nb. 7; (2005); p. 551 - 554, View in Reaxys; Piper, Brian J.; Vu, Huyen L.; Safain, Mina G.; Oliver, Andrew J.; Meyer, Jerrold S.; Journal of Pharmacology and Experimental Therapeutics; vol. 317; nb. 2; (2006); p. 838 - 849, View in Reaxys; Kelly, Paul A.T.; Ritchie, Isobel M.; Quate, Linda; McBean, Douglas E.; Olverman, Henry J.; British Journal of Pharmacology; vol. 137; nb. 7; (2002); p. 963 - 970, View in Reaxys; Partilla, John S.; Dempsey, Allison G.; Nagpal, Ameet S.; Blough, Bruce E.; Baumann, Michael H.; Rothman, Richard B.; Journal of Pharmacology and Experimental Therapeutics; vol. 319; nb. 1; (2006); p. 237 - 246, View in Reaxys; Cleary, Linda; Docherty, James R.; European Journal of Pharmacology; vol. 476; nb. 1-2; (2003); p. 31 - 34, View in Reaxys; Salzmann, Julie; Marie-Claire, Cynthia; Le Guen, Stephanie; Roques, Bernard P.; Noble, Florence; British Journal of Pharmacology; vol. 140; nb. 5; (2003); p. 831 - 838, View in Reaxys 5 of 373

Comment (Pharmacological Data)

Bioactivities present

Cornish, Jennifer L.; Shahnawaz, Zeeshan; Thompson, Murray R.; Wong, Suzanna; Morley, Kirsten C.; Hunt, Glenn E.; McGregor, Iain S.; European Journal of Pharmacology; vol. 482; nb. 1-3; (2003); p. 339 - 341, View in Reaxys; Vandeputte, Catherine; Docherty, James R; European journal of pharmacology; vol. 457; nb. 1; (2002); p. 45 - 49, View in Reaxys; Braida, Daniela; Sala, Mariaelvina; British journal of pharmacology; vol. 136; nb. 8; (2002); p. 1089 - 1092, View in Reaxys; O'Shea, Esther; Orio, Laura; Escobedo, Isabel; Sanchez, Veronica; Camarero, Jorge; Green, Alfred Richard; Colado, Maria Isabel; British Journal of Pharmacology; vol. 148; nb. 6; (2006); p. 778 - 785, View in Reaxys; Bunzow; Sonders; Arttamangkul; Harrison; Zhang; Quigley; Darland; Suchland; Pasumamula; Kennedy; Olson; Magenis; Amara; Grandy; Molecular Pharmacology; vol. 60; nb. 6; (2001); p. 1181 - 1188, View in Reaxys; Pompei, Pierluigi; Cavazzuti, Elena; Martarelli, Daniele; Pediconi, Dario; Arletti, Rossana; Lucas, Louis Ralph; Massi, Maurizio; European Journal of Pharmacology; vol. 450; nb. 3; (2002); p. 245 - 251, View in Reaxys; Bexis, Sotiria; Docherty, James R.; British Journal of Pharmacology; vol. 147; nb. 8; (2006); p. 926 - 934, View in Reaxys; Kreth, Klaus-Peter; Kovar, Karl-Artur; Schwab, Matthias; Zanger, Ulrich M.; Biochemical Pharmacology; vol. 59; nb. 12; (2000); p. 1563 - 1571, View in Reaxys; Votano, Joseph R.; Parham, Marc; Hall, L. Mark; Hall, Lowell H.; Kier, Lemont B.; Oloff, Scott; Tropsha, Alexander; Journal of Medicinal Chemistry; vol. 49; nb. 24; (2006); p. 7169 - 7181, View in Reaxys; Pacifici, Roberta; Zuccaro, Piergiorgio; Hernandez Lopez, Candido; Pichini, Simona; Di Carlo, Simonetta; Farre, Magi; Roset, Pere Nolasc; Ortuno, Jordi; Segura, Jordi; De La Torre, Rafael; Journal of Pharmacology and Experimental Therapeutics; vol. 296; nb. 1; (2001); p. 207 - 215, View in Reaxys; Sanchez; Camarero; Esteban; Peter; Green; Colado; British Journal of Pharmacology; vol. 134; nb. 1; (2001); p. 46 - 57, View in Reaxys; Cannon, Dara M.; Keenan, Alan K.; Guiry, Patrick J.; Buon, Christophe; Baird, Alan W.; McBean, Gethin J.; British Journal of Pharmacology; vol. 134; nb. 7; (2001); p. 1455 - 1460, View in Reaxys; Morley-Fletcher, Sara; Bianchi, Mauro; Gerra, Gilberto; Laviola, Giovanni; European journal of pharmacology; vol. 448; nb. 1; (2002); p. 31 - 38, View in Reaxys; Morley, Kirsten C; McGregor, Iain S; European Journal of Pharmacology; vol. 408; nb. 1; (2000); p. 41 - 49, View in Reaxys; Brammer, Matthew K.; Gilmore, Deborah L.; Matsumoto, Rae R.; European Journal of Pharmacology; vol. 553; nb. 1-3; (2006); p. 141 - 145, View in Reaxys; Nakahara, Yuji; Hanajiri, Ruri; Life Sciences; vol. 66; nb. 7; (2000); p. 563 - 574, View in Reaxys; Cleary, Linda; Buber, Robert; Docherty, James R.; European Journal of Pharmacology; vol. 451; nb. 3; (2002); p. 303 - 308, View in Reaxys; Ramamoorthy, Yamini; Yu, Ai-ming; Suh, Nina; Haining, Robert L.; Tyndale, Rachel F.; Sellers, Edward M.; Biochemical Pharmacology; vol. 63; nb. 12; (2002); p. 2111 2119, View in Reaxys; Gurtman, Clint G; Morley, Kirsten C; Li, Kong M; Hunt, Glenn E; McGregor, Iain S; European journal of pharmacology; vol. 446; nb. 1-3; (2002); p. 89 - 96, View in Reaxys; Zolkowska, Dorota; Rothman, Richard B.; Baumann, Michael H.; Journal of Pharmacology and Experimental Therapeutics; vol. 318; nb. 2; (2006); p. 604 - 610, View in Reaxys 6 of 373

Comment (Pharmacological Data)

Bioactivities present

Sprague, Jon E.; Yang, Xianmei; Sommers, Joni; Gilman, Tracy L.; Mills, Edward M.; Journal of Pharmacology and Experimental Therapeutics; vol. 320; nb. 1; (2007); p. 274 - 280, View in Reaxys; Nagai, Fumiko; Nonaka, Ryouichi; Satoh Hisashi Kamimura, Kanako; European Journal of Pharmacology; vol. 559; nb. 2-3; (2007); p. 132 - 137, View in Reaxys; Castiglioni, Sara; Zuccato, Ettore; Crisci, Elisabetta; Chiabrando, Chiara; Fanelli, Roberte; Bagnati, Renzo; Analytical Chemistry; vol. 78; nb. 24; (2006); p. 8421 - 8429, View in Reaxys; Bomsien, Stephanie; Skopp, Gisela; European Journal of Clinical Pharmacology; vol. 63; nb. 9; (2007); p. 821 - 827,

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2016-08-22 13:39:51

View in Reaxys; Goni-Allo, Beatriz; Puerta, Elena; Hervias, Isabel; Di Palma, Richard; Ramos, Maria; Lasheras, Berta; Aguirre, Norberto; European Journal of Pharmacology; vol. 562; nb. 3; (2007); p. 198 - 207, View in Reaxys; Boyle, Noreen T.; Connor, Thomas J.; European Journal of Pharmacology; vol. 572; nb. 2-3; (2007); p. 228 - 238, View in Reaxys; Rusyniak, Daniel E.; Zaretskaia, Maria V.; Zaretsky, Dmitry V.; DiMicco, Joseph A.; Journal of Pharmacology and Experimental Therapeutics; vol. 323; nb. 2; (2007); p. 477 - 487, View in Reaxys; Farre, Magi; Abanades, Sergio; Roset, Pere N.; Peiro, Ana M.; Torrens, Marta; O'Mathuna, Bryan; Segura, Mireia; De La Torre, Rafael; Journal of Pharmacology and Experimental Therapeutics; vol. 323; nb. 3; (2007); p. 954 - 962, View in Reaxys; Erives, Gladys V.; Lau, Serrine S.; Monks, Terrence J.; Journal of Pharmacology and Experimental Therapeutics; vol. 324; nb. 1; (2008); p. 284 - 291, View in Reaxys; Mas, Marta; Farre, Magi; De la Torre, Rafael; Roset, Pere N.; Ortuno, Jordi; Segura, Jordi; Cami, Jordi; Journal of Pharmacology and Experimental Therapeutics; vol. 290; nb. 1; (1999); p. 136 - 145, View in Reaxys; McNamara, Ruth; Maginn, Mark; Harkin, Andrew; European Journal of Pharmacology; vol. 555; nb. 2-3; (2007); p. 194 - 198, View in Reaxys; Patent; Ekins, Sean; US2002/13372; (2002); (A1) English, View in Reaxys; Patent; Owens, Samuel M.; Carroll, Frank Ivy; Abraham, Philip; US2001/51158; (2001); (A1) English, View in Reaxys; Shima; Katagi; Kamata; Zaitsu; Nishikawa; Miki; Tsuchihashi; Sakuma; Nemoto; Xenobiotica; vol. 38; nb. 3; (2008); p. 314 324, View in Reaxys; Postigo, Cristina; Lopez De Alda, Maria J.; Barcelo, Damia; Analytical Chemistry; vol. 80; nb. 9; (2008); p. 3123 - 3134, View in Reaxys; Buchanan, Hilary A. S.; Daeid, Niamh Nic; Meier-Augenstein, Wolfram; Kemp, Helen F.; Kerr, William J.; Middleditch, Michael; Analytical Chemistry; vol. 80; nb. 9; (2008); p. 3350 - 3356, View in Reaxys; Upreti, Vijay V.; Eddington, Natalie D.; Journal of Pharmaceutical Sciences; vol. 97; nb. 4; (2008); p. 1593 - 1605, View in Reaxys; Huerta-Fontela, Maria; Galceran, Maria Teresa; Ventura, Francesc; Environmental Science and Technology; vol. 42; nb. 18; (2008); p. 6809 - 6816, View in Reaxys; West, Matthew J.; Went, Michael J.; Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy; vol. 71; nb. 5; (2009); p. 1984 - 1988, View in Reaxys; Thoerngren, John-Olof; Oestervall, Fredrik; Garle, Mats; Journal of Mass Spectrometry; vol. 43; nb. 7; (2008); p. 980 - 992, View in Reaxys 7 of 373

Comment (Pharmacological Data)

Bioactivities present

Cloonan, Suzanne M.; Keating, John J.; Butler, Stephen G.; Knox, Andrew J.S.; Jorgensen, Anne M.; Peters, Guenther H.; Rai, Dilip; Corrigan, Desmond; Lloyd, David G.; Williams, D. Clive; Meegan, Mary J.; European Journal of Medicinal Chemistry; vol. 44; nb. 12; (2009); p. 4862 - 4888, View in Reaxys; Patent; DADE BEHRING INC.; WO2005/61482; (2005); (A1) English, View in Reaxys; Schulze, Matthias; Synthetic Communications; vol. 40; nb. 10; (2010); p. 1461 - 1476, View in Reaxys; Inoue, Hiroyuki; Hashimoto, Hiroaki; Watanabe, Susumu; Iwata, Yuko T.; Kanamori, Tatsuyuki; Miyaguchi, Hajime; Tsujikawa, Kenji; Kuwayama, Kenji; Tachi, Noriyuki; Uetake, Naohito; Journal of Mass Spectrometry; vol. 44; nb. 9; (2009); p. 1300 - 1307, View in Reaxys; Cloonan, Suzanne M.; Keating, John J.; Corrigan, Desmond; O'Brien, John E.; Kavanagh, Pierce V.; Williams, D. Clive; Meegan, Mary J.; Bioorganic and Medicinal Chemistry; vol. 18; nb. 11; (2010); p. 4009 - 4031, View in Reaxys; Patent; ABBOTT GMBH and CO. KG; WO2006/40180; (2006); (A1) English, View in Reaxys; Guillarme, Davy; Bonvin, Gregoire; Badoud, Flavia; Schappler, Julie; Rudaz, Serge; Veuthey, Jean-Luc; Chirality; vol. 22; nb. 3; (2010); p. 320 - 330, View in Reaxys; Vanattou-Saifoudine; McNamara; Harkin; British Journal of Pharmacology; vol. 160; nb. 4; (2010); p. 860 - 877, View in Reaxys; McNamara, Yvonne M.; Cloonan, Suzanne M.; Knox, Andrew J.S.; Keating, John J.; Butler, Stephen G.; Peters, Guenther H.; Meegan, Mary J.; Williams, D. Clive; Bioorganic and Medicinal Chemistry; vol. 19; nb. 3; (2011); p. 1328 - 1348, View in Reaxys; Antolino-Lobo, Irene; Meulenbelt, Jan; Nijmeijer, Sandra M.; Scherpenisse, Peter; Van Den Berg, Martin; Van Duursen, Majorie B. M.; Drug Metabolism and Disposition; vol. 38; nb. 7; (2010); p. 1105 - 1112, View in Reaxys; Vonaparti; Lyris; Angelis; Panderi; Koupparis; Tsantili-Kakoulidou; Peters; Nielen; Georgakopoulos; Rapid Communications in Mass Spectrometry; vol. 24; nb. 11; (2010); p. 1595 - 1609, View in Reaxys; Bosker, Wendy M.; Kuypers, Kim P. C.; Conen, Silke; Ramaekers, Johannes G.; Psychopharmacology; vol. 209; nb. 1; (2010); p. 69 - 76, View in Reaxys; Bijlsma, Lubertus; Sancho, Juan V.; Hernandez, Felix; Niessen, Wilfried M.A.; Journal of Mass Spectrometry; vol. 46; nb. 9; (2011); p. 865 - 875, View in Reaxys; Lewin, Anita H.; Miller, Gregory M.; Gilmour, Brian; Bioorganic and Medicinal Chemistry; vol. 19; nb. 23; (2011); p. 7044 - 7048, View in Reaxys; Lansbergen, Marieke M.; Dumont, Glenn J. H.; Van Gerven, Joop M. A.; Buitelaar, Jan K.; Verkes, Robbert-Jan; Psychopharmacology; vol. 213; nb. 4; (2011); p. 745 - 756, View in Reaxys; Stewart, Adam; Riehl, Russell; Wong, Keith; Green, Jeremy; Cosgrove, Jessica; Vollmer, Karoly; Kyzar, Evan; Hart, Peter; Allain, Alexander; Cachat, Jonathan; Gaikwad, Siddharth; Hook, Molly; Rhymes, Kate; Newman, Alan; Utterback, Eli; Chang, Katie; Kalueff, Allan V.; Behavioural Pharmacology; vol. 22; nb. 3; (2011); p. 275 - 280, View in Reaxys; Kehr; Ichinose; Yoshitake; Goiny; Sievertsson; Nyberg; British Journal of Pharmacology; vol. 164; nb. 8; (2011); p. 1949 - 1958, View in Reaxys; Cerretani; Bello; Cantatore; Fiaschi; Montefrancesco; Neri; Pomara; Riezzo; Fiore; Bonsignore; Turillazzi; Fineschi; Pharmacological Research; vol. 64; nb. 5; (2011); p. 517 - 527, View in Reaxys; Ghanbari; Rowland-Yeo; Bloomer; Clarke; Lennard; Tucker; Rostami-Hodjegan; Current Drug Metabolism; vol. 7; nb. 3; (2006); p. 315 - 334, View in Reaxys; Amphoux, Anne; Vialou, Vincent; Drescher, Eva; Bruess, Michael; La Cour, Clotilde Mannoury; Rochat, Catherine; Millan, Mark J.; Giros, Bruno; Boenisch, Heinz; Gautron, Sophie; Neuropharmacology; vol. 50; nb. 8; (2006); p. 941 - 952, View in Reaxys 8 of 373

Comment (Pharmacological Data)

Bioactivities present

Rothman, Richard B.; Baumann, Michael H.; Current Topics in Medicinal Chemistry; vol. 6; nb. 17; (2006); p. 1845 - 1859, View in Reaxys; Fontana; Dansette, Patrick M.; Poli, Sonia Maria; Current Drug Metabolism; vol. 6; nb. 5; (2005); p. 413 - 454, View in Reaxys; Atkinson, Anthony; Kenny, Jane R.; Grime, Ken; Drug Metabolism and Disposition; vol. 33; nb. 11; (2005); p. 1637 - 1647, View in Reaxys; Obach, R. Scott; Walsky, Robert L.; Venkatakrishnan, Karthik; Drug Metabolism and Disposition; vol. 35; nb. 2; (2007); p. 246 - 255, View in Reaxys;

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Crowe, Andrew; Diep, Susanna; European Journal of Pharmacology; vol. 592; nb. 1-3; (2008); p. 7 - 12, View in Reaxys; Meyer, Markus R.; Peters, Frank T.; Maurer, Hans H.; Drug Metabolism and Disposition; vol. 36; nb. 11; (2008); p. 2345 - 2354, View in Reaxys; Goncalves, Pedro; Araujo, Joao Ricardo; Pinho, Maria Joao; Martel, Fatima; Naunyn-Schmiedeberg's Archives of Pharmacology; vol. 379; nb. 4; (2009); p. 325 - 336, View in Reaxys; Grime, Kenneth H.; Bird, James; Ferguson, Douglas; Riley, Robert J.; European Journal of Pharmaceutical Sciences; vol. 36; nb. 2-3; (2009); p. 175 - 191, View in Reaxys; Zhou, Shu-Feng; Liu, Jun-Ping; Lai, Xin-Sheng; Current Medicinal Chemistry; vol. 16; nb. 21; (2009); p. 2661 - 2805, View in Reaxys; AntolinoLobo, Irene; Meulenbelt, Jan; Nijmeijer, Sandra M.; Maas-Bakker, Roel F.; Meijerman, Irma; van den Berg, Martin; van Duursen, Majorie B.M.; Toxicology Letters; vol. 203; nb. 1; (2011); p. 82 - 91, View in Reaxys; Gandy, Michael N.; McIldowie, Matthew; Lewis, Katie; Wasik, Agata M.; Salomonczyk, Danielle; Wagg, Keith; Millar, Zak A.; Tindiglia, David; Huot, Philippe; Johnston, Tom; Thiele, Sherri; Nguyen, Blake; Barnes, Nicholas M.; Brotchie, Jonathan M.; Martin-Iverson, Mathew T.; Nash, Joanne; Gordon, John; Piggott, Matthew J.; MedChemComm; vol. 1; nb. 4; (2010); p. 287 - 293, View in Reaxys; Sjoegren, Erik; Nyberg, Joakim; Magnusson, Mats O.; Lennernaes, Hans; Hooker, Andrew; Bredberg, Ulf; Drug Metabolism and Disposition; vol. 39; nb. 5; (2011); p. 858 - 863, View in Reaxys; Niwa, Toshiro; Murayama, Norie; Yamazaki, Hiroshi; Current Drug Metabolism; vol. 12; nb. 5; (2011); p. 412 - 435, View in Reaxys; Mueller, Melanie; Goodwin, Amy K.; Ator, Nancy A.; McCann, Una D.; Ricaurte, George A.; Journal of Pharmacology and Experimental Therapeutics; vol. 338; nb. 1; (2011); p. 310 - 317, View in Reaxys; Banister, Samuel D.; Kassiou, Michael; Current Pharmaceutical Design; vol. 18; nb. 7; (2012); p. 884 - 901, View in Reaxys; Vircks, Kyle E.; Mulligan, Christopher C.; Rapid Communications in Mass Spectrometry; vol. 26; nb. 23; (2012); p. 2665 - 2672, View in Reaxys; Schaper, J. Niklas; Pfeuffer, Kevin P.; Shelley, Jacob T.; Bings, Nicolas H.; Hieftje, Gary M.; Analytical Chemistry; vol. 84; nb. 21; (2012); p. 9246 9252, View in Reaxys; Montesano, Camilla; Sergi, Manuel; Moro, Mariaelena; Napoletano, Sabino; Romolo, Francesco Saverio; Carlo, Michele Del; Compagnone, Dario; Curini, Roberta; Journal of Mass Spectrometry; vol. 48; nb. 1; (2013); p. 49 - 59, View in Reaxys; Fedorova, Ganna; Randak, Tomas; Lindberg, Richard H.; Grabic, Roman; Rapid Communications in Mass Spectrometry; vol. 27; nb. 15; (2013); p. 1751 - 1762, View in Reaxys; Goodwin, Amy K.; Mueller, Melanie; Shell, Courtney D.; Ricaurte, George A.; Ator, Nancy A.; Journal of Pharmacology and Experimental Therapeutics; vol. 345; nb. 3; (2013); p. 342 - 353, View in Reaxys 9 of 373

Comment (Pharmacological Data)

Bioactivities present

Farre; De La Torre; Mathuna; Roset; Peiro; Torrens; Ortuno; Pujadas; Cami; Psychopharmacology; vol. 173; nb. 3-4; (2004); p. 364 - 375, View in Reaxys; Pizarro, Nieves; Farre, Magi; Pujadas, Mitona; Peiro, Ana Ma.; Roset, Pere N.; Joglar, Jesus; De La Torre, Rafael; Drug Metabolism and Disposition; vol. 32; nb. 9; (2004); p. 1001 - 1007, View in Reaxys; Heydari; Rowland Yeo; Lennard; Ellis; Tucker; Rostami-Hodjegan; Drug Metabolism and Disposition; vol. 32; nb. 11; (2004); p. 1213 - 1217, View in Reaxys; Lewis, David F.V.; Current Medicinal Chemistry; vol. 10; nb. 19; (2003); p. 1955 - 1972, View in Reaxys; Gesi, Marco; Soldani, Paola; Lenzi, Paola; Ferrucci, Michela; Giusiani, Alberto; Fornai, Francesco; Paparelli, Antonio; Pharmacology and Toxicology; vol. 91; nb. 1; (2002); p. 29 - 33, View in Reaxys; Morley-Fletcher, Sara; Bianchi, Mauro; Gerra, Gilberto; Laviola, Giovanni; European Journal of Pharmacology; vol. 448; nb. 1; (2002); p. 31 - 38, View in Reaxys; Braida, Daniela; Sala, Mariaelvina; British Journal of Pharmacology; vol. 136; nb. 8; (2002); p. 1089 - 1092, View in Reaxys; Vandeputte, Catherine; Docherty, James R.; European Journal of Pharmacology; vol. 457; nb. 1; (2002); p. 45 - 49, View in Reaxys; Ramamoorthy, Yamini; Yu, Ai-ming; Suh, Nina; Haining, Robert L; Tyndale, Rachel F; Sellers, Edward M; Biochemical pharmacology; vol. 63; nb. 12; (2002); p. 2111 - 2119, View in Reaxys; Gurtman, Clint G; Morley, Kirsten C; Li, Kong M; Hunt, Glenn E; McGregor, Iain S; European Journal of Pharmacology; vol. 446; nb. 1-3; (2002); p. 89 - 96, View in Reaxys; Ramamoorthy; Tyndale; Sellers; Pharmacogenetics; vol. 11; nb. 6; (2001); p. 477 - 487, View in Reaxys; Lin; Di Stefano; Schmitz; Hsu; Ellis; Lennard; Tucker; Cho; Drug Metabolism and Disposition; vol. 25; nb. 9; (1997); p. 1059 - 1064, View in Reaxys; Colado; Green; European Journal of Pharmacology; vol. 280; nb. 3; (1995); p. 343 - 346, View in Reaxys; Aguirre; Galbete; Lasheras; Del Rio; European Journal of Pharmacology; vol. 281; nb. 1; (1995); p. 101 - 105, View in Reaxys; Komagai; Schmitz; Cho; Xenobiotica; vol. 22; nb. 4; (1992); p. 395 - 403, View in Reaxys; Nichols; Brewster; Johnson; Oberlender; Riggs; Journal of Medicinal Chemistry; vol. 33; nb. 2; (1990); p. 703 - 710, View in Reaxys; Oberlender; Nichols; Psychopharmacology; vol. 95; nb. 1; (1988); p. 71 - 76, View in Reaxys; Lyon; Glennon; Titeler; Psychopharmacology; vol. 88; nb. 4; (1986); p. 525 - 526, View in Reaxys; Nichols; Lloyd; Hoffman; Yim; Journal of Medicinal Chemistry; vol. 25; nb. 5; (1982); p. 530 - 535, View in Reaxys; Braun; Shulgin; Arzneimittel-Forschung/Drug Research; vol. 30; nb. 5; (1980); p. 825 - 830, View in Reaxys 10 of 373

Comment (Pharmacological Data)

Bioactivities present

Huang, Min-Zong; Zhou, Chi-Chang; Liu, De-Lin; Jhang, Siou-Sian; Cheng, Sy-Chyi; Shiea, Jentaie; Analytical Chemistry; vol. 85; nb. 19; (2013); p. 8956 - 8963, View in Reaxys; Broadley, Kenneth J.; Fehler, Martina; Ford, William R.; Kidd, Emma J.; European Journal of Pharmacology; vol. 715; nb. 1-3; (2013); p. 370 - 380, View in Reaxys; Kirk M. Bertelsen 1, David J. Greenblatt 1 2 *, Lisa L. von Moltke 1 2; Biopharmaceutics & drug disposition; vol. 27; (2006); p. 219, View in Reaxys; ; (2012); Type: Review, Lab: EFF_071212, Owner: EFFECT, Number: 000, Revision: 07.12.2012 00:00:00, View in Reaxys; Concheiro, Marta; Baumann, Michael H.; Scheidweiler, Karl B.; Rothman, Richard B.; Marrone, Gina F.; Huestis, Marilyn A.; Drug Metabolism and Disposition; vol. 42; nb. 1; (2014); p. 119 - 125, View in Reaxys; Warunya Arunotayanun; Jeffrey W. Dalley; Xi-Ping Huang; Vincent Setola; Ric Treble; Leslie Iversen; Bryan L. Roth; Simon Gibbons; Bioorganic & medicinal chemistry letters; vol. 23; nb. 11; (2013); p. 3411 - 3415, View in Reaxys; Clarke's Analysis of Drugs and Poisons, View in Reaxys; Material Safety Data Sheet, View in Reaxys; Patent; Beth J. Hoffman; Eva Mezey; Michael J. Brownstein; US5552308; (A); (1996), View in Reaxys; Fuchigami Yuki; Ikeda Rie; Kuzushima Miki; Wada Mitsu-

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hiro; Kuroda Naotaka; Nakashima Kenichiro; European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences; vol. 49; nb. 1; (2013); p. 57 - 64, View in Reaxys; Eshleman, Amy J.; Forster, Michael J.; Wolfrum, Katherine M.; Johnson, Robert A.; Janowsky, Aaron; Gatch, Michael B.; Psychopharmacology; vol. 231; nb. 5; (2014); p. 875 - 888, View in Reaxys; Stojanovska, Natasha; Kelly, Tamsin; Tahtouh, Mark; Beavis, Alison; Fu, Shanlin; Rapid Communications in Mass Spectrometry; vol. 28; nb. 7; (2014); p. 731 - 740, View in Reaxys; Abad, Sonia; Fole, Alberto; Del Olmo, Nuria; Pubill, David; Pallas, Merce; Junyent, Felix; Camarasa, Jorge; Camins, Antonio; Escubedo, Elena; Psychopharmacology; vol. 231; nb. 5; (2014); p. 863 - 874, View in Reaxys; Fisk, John E.; Gallagher, Denis T.; Hadjiefthyvoulou, Florentia; Montgomery, Catharine; Human Psychopharmacology; vol. 29; nb. 2; (2014); p. 172 - 182, View in Reaxys; Merck; Priv.-Mitt. 1952, View in Reaxys; Hendricks, Paul I.; Dalgleish, Jon K.; Shelley, Jacob T.; Kirleis, Matthew A.; McNicholas, Matthew T.; Li, Linfan; Chen, Tsung-Chi; Chen, Chien-Hsun; Duncan, Jason S.; Boudreau, Frank; Noll, Robert J.; Denton, John P.; Roach, Timothy A.; Ouyang, Zheng; Cooks, R. Graham; Analytical Chemistry; vol. 86; nb. 6; (2014); p. 2900 - 2908, View in Reaxys; Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46, View in Reaxys; Taschwer, Magdalena; Seidl, Yvonne; Mohr, Stefan; Schmid, Martin G.; Chirality; vol. 26; nb. 8; (2014); p. 411 - 418, View in Reaxys; Espy, Ryan D.; Teunissen, Sebastiaan Frans; Manicke, Nicholas E.; Ren, Yue; Ouyang, Zheng; Van Asten, Arian; Cooks, R. Graham; Analytical Chemistry; vol. 86; nb. 15; (2014); p. 7712 - 7718, View in Reaxys; Lin, Huei-Ru; Liao, Chao-Chuan; Lin, Tzu-Chieh; Rapid Communications in Mass Spectrometry; vol. 28; nb. 19; (2014); p. 2043 - 2053, View in Reaxys 11 of 373

Comment (Pharmacological Data)

Bioactivities present

Patent; PHILADELPHIA HEALTH AND EDUCATION CORPORATION D/B/A DREXEL UNIVERSITY COLLEGE OF MEDICINE; KORTAGERE, Sandhya; MORTENSEN, Ole Valente; MORTENSEN, Andreia C.K.; WO2014/172453; (2014); (A2) English, View in Reaxys; De Sousa Fernandes Perna; Theunissen; Kuypers; Heckman; De La Torre; Farre; Ramaekers; Neuropharmacology; vol. 87; (2014); p. 198 - 205, View in Reaxys; Dinger, Julia; Meyer, Markus R.; Maurer, Hans H.; Archives of Toxicology; vol. 90; nb. 2; (2016); p. 305 - 318, View in Reaxys; Spinner; Klima; Kempf; Huppertz; Auwärter; Altenburger; Neukamm; Journal of Mass Spectrometry; vol. 49; nb. 12; (2014); p. 1306 - 1313, View in Reaxys; Roemmelt, Andreas T.; Steuer, Andrea E.; Poetzsch, Michael; Kraemer, Thomas; Analytical Chemistry; vol. 86; nb. 23; (2014); p. 11742 - 11749, View in Reaxys; Pifl, Christian; Reither, Harald; Hornykiewicz, Oleh; European Journal of Pharmacology; vol. 755; (2015); p. 119 - 126, View in Reaxys; Alsufyani, Hadeel A.; Docherty, James R.; European Journal of Pharmacology; vol. 758; (2015); p. 142 - 146; Art.No: 69883, View in Reaxys; Jeong, Eun Sook; Kim, So-Hee; Cha, Eun-Ju; Lee, Kang Mi; Kim, Ho Jun; Lee, Sang-Won; Kwon, Oh-Seung; Lee, Jaeick; Rapid Communications in Mass Spectrometry; vol. 29; nb. 4; (2015); p. 367 - 384, View in Reaxys; Jeong, Eun Sook; Kim, So-Hee; Cha, Eun-Ju; Lee, Kang Mi; Kim, Ho Jun; Lee, Sang-Won; Kwon, Oh-Seung; Lee, Jaeick; Rapid Communications in Mass Spectrometry; vol. 29; nb. 4; (2015); p. 367 - 384, View in Reaxys; Collins, Stuart A.; Gudelsky, Gary A.; Yamamoto, Bryan K.; European Journal of Pharmacology; vol. 761; (2015); p. 95 - 100; Art.No: 69923, View in Reaxys; Singer, Lynn T.; Moore, Derek G.; Min, Meeyoung O.; Goodwin, Julia; Turner, John J. D.; Fulton, Sarah; Parrott, Andrew C.; Human Psychopharmacology; vol. 30; nb. 4; (2015); p. 290 - 294, View in Reaxys; Chapy, Hlne; Goracci, Laura; Vayer, Philippe; Parmentier, Yannick; Carrupt, Pierre-Alain; Declves, Xavier; Scherrmann, Jean-Michel; Cisternino, Salvatore; Cruciani, Gabriele; British Journal of Pharmacology; vol. 172; nb. 20; (2015); p. 4888 - 4904, View in Reaxys; Del Bello, Fabio; Sakloth, Farhana; Partilla, John S.; Baumann, Michael H.; Glennon, Richard A.; Bioorganic and Medicinal Chemistry; vol. 23; nb. 17; (2015); p. 5574 - 5579, View in Reaxys; Patent; Randox Laboratories Ltd.; Benchik, Elouard; Fitzgerald, Peter; Lowry, Philip; McConnell, Ivan; EP2950104; (2015); (A1) English, View in Reaxys; Duvivier, Wilco F.; Van Putten, Marc R.; Van Beek, Teris A.; Nielen, Michel W. F.; Analytical Chemistry; vol. 88; nb. 4; (2016); p. 2489 - 2496, View in Reaxys; Macúchová; Ševčíková; Hrebíčková; Nohejlová; Šlamberová; International Journal of Developmental Neuroscience; vol. 51; (2016); p. 1 - 11, View in Reaxys; Silva, Sónia; Carvalho, Félix; Fernandes, Eduarda; Antunes, Manuel J.; Cotrim, Maria Dulce; Toxicology in Vitro; vol. 34; (2016); p. 187 - 193, View in Reaxys; Gatch, Michael B.; Forster, Michael J.; Psychopharmacology; vol. 233; nb. 10; (2016); p. 1901 - 1910, View in Reaxys; Palamar, Joseph J.; Salomone, Alberto; Vincenti, Marco; Cleland, Charles M.; Drug and Alcohol Dependence; vol. 161; (2016); p. 200 - 205, View in Reaxys; Pérez, Rocío L.; Escandar, Graciela M.; Sustainable Chemistry and Pharmacy; vol. 4; (2016); p. 1 - 12, View in Reaxys 12 of 373

Comment (Pharmacological Data)

Bioactivities present

Gatidou, Georgia; Kinyua, Juliet; van Nuijs, Alexander L.N.; Gracia-Lor, Emma; Castiglioni, Sara; Covaci, Adrian; Stasinakis, Athanasios S.; Science of the Total Environment; vol. 563-564; (2016); p. 633 - 640, View in Reaxys; Zaami, Simona; De-Giorgio, Fabio; Marinelli, Enrico; Pellegrini, Manuela; Pichini, Simona; Busardò, Francesco P.; International Journal of Cardiology; vol. 220; (2016); p. 835 - 836, View in Reaxys; Rojek, Sebastian; Bolechała, Filip; Kula, Karol; Maciów-Głąb, Martyna; Kłys, Małgorzata; Legal Medicine; vol. 21; (2016); p. 64 - 72, View in Reaxys; Abad, Sonia; Ramon, Carla; Pubill, David; Camarasa, Jorge; Camins, Antonio; Escubedo, Elena; Biochimica et Biophysica Acta - Molecular Basis of Disease; vol. 1862; nb. 9; (2016); p. 1815 - 1826, View in Reaxys; García-Cabrerizo, Rubén; García-Fuster, M. Julia; NeuroToxicology; vol. 56; (2016); p. 29 - 39, View in Reaxys; Heifets, Boris D.; Malenka, Robert C.; Cell; vol. 166; nb. 2; (2016); p. 269 - 272, View in Reaxys; Rosas-Hernandez, Hector; Cuevas, Elvis; Lantz, Susan M.; Rice, Kenner C.; Gannon, Brenda M.; Fantegrossi, William E.; Gonzalez, Carmen; Paule, Merle G.; Ali, Syed F.; Neuroscience Letters; vol. 629; (2016); p. 125 - 130, View in Reaxys; Soyka, Michael; Mutschler, Jochen; Progress in Neuro-Psychopharmacolo-

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gy and Biological Psychiatry; vol. 70; (2016); p. 148 - 161, View in Reaxys; Tscharke, Benjamin J.; Chen, Chang; Gerber, Jacobus P.; White, Jason M.; Science of the Total Environment; vol. 565; (2016); p. 384 - 391, View in Reaxys; Frau, Lucia; Simola, Nicola; Porceddu, Pier Francesca; Morelli, Micaela; NeuroToxicology; vol. 56; (2016); p. 127 - 138, View in Reaxys; Taghizadeh, Ghorban; Pourahmad, Jalal; Mehdizadeh, Hajar; Foroumadi, Alireza; Torkaman-Boutorabi, Anahita; Hassani, Shokoufeh; Naserzadeh, Parvaneh; Shariatmadari, Reyhaneh; Gholami, Mahdi; Rouini, Mohammad Reza; Sharifzadeh, Mohammad; Free Radical Biology and Medicine; vol. 99; (2016); p. 11 - 19, View in Reaxys; Koek, Ralph J.; Schwartz, Holly N.; Scully, Stephenie; Langevin, Jean-Philippe; Spangler, Shana; Korotinsky, Arkady; Jou, Kevin; Leuchter, Andrew; Progress in NeuroPsychopharmacology and Biological Psychiatry; vol. 70; (2015); p. 170 - 218, View in Reaxys 13 of 373

Comment (Pharmacological Data)

physiological behaviour discussed

Dinger, Julia; Meyer, Markus R.; Maurer, Hans H.; Archives of Toxicology; vol. 90; nb. 2; (2016); p. 305 - 318, View in Reaxys 14 of 373

Comment (Pharmacological Data)

physiological behaviour discussed

Macúchová; Ševčíková; Hrebíčková; Nohejlová; Šlamberová; International Journal of Developmental Neuroscience; vol. 51; (2016); p. 1 - 11, View in Reaxys 15 of 373

Comment (Pharmacological Data)

physiological behaviour discussed

Silva, Sónia; Carvalho, Félix; Fernandes, Eduarda; Antunes, Manuel J.; Cotrim, Maria Dulce; Toxicology in Vitro; vol. 34; (2016); p. 187 - 193, View in Reaxys 16 of 373

Comment (Pharmacological Data)

physiological behaviour discussed

Collins, Stuart A.; Gudelsky, Gary A.; Yamamoto, Bryan K.; European Journal of Pharmacology; vol. 761; (2015); p. 95 - 100; Art.No: 69923, View in Reaxys 17 of 373

Comment (Pharmacological Data)

physiological behaviour discussed

Alsufyani, Hadeel A.; Docherty, James R.; European Journal of Pharmacology; vol. 758; (2015); p. 142 - 146; Art.No: 69883, View in Reaxys 18 of 373

Comment (Pharmacological Data)

physiological behaviour discussed

Pifl, Christian; Reither, Harald; Hornykiewicz, Oleh; European Journal of Pharmacology; vol. 755; (2015); p. 119 - 126, View in Reaxys 19 of 373

Comment (Pharmacological Data)

physiological behaviour discussed

Singer, Lynn T.; Moore, Derek G.; Min, Meeyoung O.; Goodwin, Julia; Turner, John J. D.; Fulton, Sarah; Parrott, Andrew C.; Human Psychopharmacology; vol. 30; nb. 4; (2015); p. 290 - 294, View in Reaxys 20 of 373

Comment (Pharmacological Data)

physiological behaviour discussed

Chapy, Hlne; Goracci, Laura; Vayer, Philippe; Parmentier, Yannick; Carrupt, Pierre-Alain; Declves, Xavier; Scherrmann, Jean-Michel; Cisternino, Salvatore; Cruciani, Gabriele; British Journal of Pharmacology; vol. 172; nb. 20; (2015); p. 4888 - 4904, View in Reaxys 21 of 373

Comment (Pharmacological Data)

physiological behaviour discussed

Patent; Randox Laboratories Ltd.; Benchik, Elouard; Fitzgerald, Peter; Lowry, Philip; McConnell, Ivan; EP2950104; (2015); (A1) English, View in Reaxys 22 of 373

Comment (Pharmacological Data)

physiological behaviour discussed

Eshleman, Amy J.; Forster, Michael J.; Wolfrum, Katherine M.; Johnson, Robert A.; Janowsky, Aaron; Gatch, Michael B.; Psychopharmacology; vol. 231; nb. 5; (2014); p. 875 - 888, View in Reaxys 23 of 373

Comment (Pharmacological Data)

physiological behaviour discussed

Abad, Sonia; Fole, Alberto; Del Olmo, Nuria; Pubill, David; Pallas, Merce; Junyent, Felix; Camarasa, Jorge; Camins, Antonio; Escubedo, Elena; Psychopharmacology; vol. 231; nb. 5; (2014); p. 863 - 874, View in Reaxys

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24 of 373

Comment (Pharmacological Data)

physiological behaviour discussed

Fisk, John E.; Gallagher, Denis T.; Hadjiefthyvoulou, Florentia; Montgomery, Catharine; Human Psychopharmacology; vol. 29; nb. 2; (2014); p. 172 - 182, View in Reaxys 25 of 373

Comment (Pharmacological Data)

physiological behaviour discussed

Concheiro, Marta; Baumann, Michael H.; Scheidweiler, Karl B.; Rothman, Richard B.; Marrone, Gina F.; Huestis, Marilyn A.; Drug Metabolism and Disposition; vol. 42; nb. 1; (2014); p. 119 - 125, View in Reaxys 26 of 373

Comment (Pharmacological Data)

physiological behaviour discussed

Comment (Pharmacological Data)

physiological behaviour discussed

Comment (Pharmacological Data)

physiological behaviour discussed

De Sousa Fernandes Perna; Theunissen; Kuypers; Heckman; De La Torre; Farre; Ramaekers; Neuropharmacology; vol. 87; (2014); p. 198 - 205, View in Reaxys 29 of 373

Comment (Pharmacological Data)

physiological behaviour discussed

Goodwin, Amy K.; Mueller, Melanie; Shell, Courtney D.; Ricaurte, George A.; Ator, Nancy A.; Journal of Pharmacology and Experimental Therapeutics; vol. 345; nb. 3; (2013); p. 342 - 353, View in Reaxys 30 of 373

Comment (Pharmacological Data)

physiological behaviour discussed

Broadley, Kenneth J.; Fehler, Martina; Ford, William R.; Kidd, Emma J.; European Journal of Pharmacology; vol. 715; nb. 1-3; (2013); p. 370 - 380, View in Reaxys 31 of 373

Effect (Pharmacological Data)

cytotoxic

Species or Test-System (Pharmacological Data)

HEK293 cells

Further Details (Pharmacological Data)

neutral red assay; HEK: human embryonic kidney; effective concentration (EC)

Type (Pharmacological Data)

log EC50

Value of Type (Pharmacological Data)

-3.6

McNamara, Yvonne M.; Cloonan, Suzanne M.; Knox, Andrew J.S.; Keating, John J.; Butler, Stephen G.; Peters, Guenther H.; Meegan, Mary J.; Williams, D. Clive; Bioorganic and Medicinal Chemistry; vol. 19; nb. 3; (2011); p. 1328 - 1348, View in Reaxys 32 of 373

Effect (Pharmacological Data)

cytotoxic

Species or Test-System (Pharmacological Data)

HEK293 cells; genetically modified/infected with: human serotonin transporter

Further Details (Pharmacological Data)

neutral red assay; HEK: human embryonic kidney; effective concentration (EC)

Type (Pharmacological Data)

log EC50

Value of Type (Pharmacological Data)

-3.3

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Effect (Pharmacological Data)

cytotoxic

Species or Test-System (Pharmacological Data)

DG-75 cells

Further Details (Pharmacological Data)

DG-75 cells: B-lymphocyte Burkitt's lymphoma cell line derived from lung metastatic pleural effusion of Burkitt's lymphoma sporadic case; neutral red assay; effective concentration (EC)

Type (Pharmacological Data)

log EC50

Value of Type (Pharmacological Data)

-4.5

Effect (Pharmacological Data)

cytotoxic

Species or Test-System (Pharmacological Data)

SHSY-5Y cells

Further Details (Pharmacological Data)

SHSY-5Y cells: thrice cloned (SK-N-SH->SH-SY->SH-SY5->SH-SY5Y) subline of human neuroblastoma cell line SK-N-SH established from metastatic bone tumour; neutral red assay; effective concentration (EC)

Type (Pharmacological Data)

log EC50

Value of Type (Pharmacological Data)

> -2

Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

human

Route of Application

peroral

Concentration (Pharmacological Data)

100 mg

Kind of Dosing (Pharmacological Data)

titel comp. administered with or without ethanol or delta-9-tetrahydrocannabinol

Further Details (Pharmacological Data)

kinetics did not differ between single or combined title comp. administration; peak concentration related to: plasma

Type (Pharmacological Data)

peak concentration

Value of Type (Pharmacological Data)

202.5 - 213.3 μg/l

Lansbergen, Marieke M.; Dumont, Glenn J. H.; Van Gerven, Joop M. A.; Buitelaar, Jan K.; Verkes, RobbertJan; Psychopharmacology; vol. 213; nb. 4; (2011); p. 745 - 756, View in Reaxys 36 of 373

Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

human

Route of Application

peroral

16/242

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Concentration (Pharmacological Data)

100 mg

Kind of Dosing (Pharmacological Data)

titel comp. administered with or without ethanol or delta-9-tetrahydrocannabinol

Further Details (Pharmacological Data)

kinetics did not differ between single or combined title comp. administration; time to Cmax related to: plasma

Type (Pharmacological Data)

time to Cmax

Value of Type (Pharmacological Data)

105 - 150 min

Lansbergen, Marieke M.; Dumont, Glenn J. H.; Van Gerven, Joop M. A.; Buitelaar, Jan K.; Verkes, RobbertJan; Psychopharmacology; vol. 213; nb. 4; (2011); p. 745 - 756, View in Reaxys 37 of 373

Effect (Pharmacological Data)

c-fos expression; increase of

Species or Test-System (Pharmacological Data)

Danio rerio, zebrafish

Sex

male and female

Kind of Dosing (Pharmacological Data)

fish immersed in 1 L plastic beaker containing 40 - 80 mg/l of title comp. in water for 20 min

Further Details (Pharmacological Data)

5-7-month-old fish used; real time-PCR; fold increase related to: brain

Type (Pharmacological Data)

fold increase

Value of Type (Pharmacological Data)

12.3 - 26.6 μmol/l

Stewart, Adam; Riehl, Russell; Wong, Keith; Green, Jeremy; Cosgrove, Jessica; Vollmer, Karoly; Kyzar, Evan; Hart, Peter; Allain, Alexander; Cachat, Jonathan; Gaikwad, Siddharth; Hook, Molly; Rhymes, Kate; Newman, Alan; Utterback, Eli; Chang, Katie; Kalueff, Allan V.; Behavioural Pharmacology; vol. 22; nb. 3; (2011); p. 275 - 280, View in Reaxys 38 of 373

Effect (Pharmacological Data)

neurotransmitter level; increase of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

3 mg/kg

Kind of Dosing (Pharmacological Data)

comparative comp. dissolved in saline

Further Details (Pharmacological Data)

microdialysis; mass of species: 300 - 350 g; dopamine extracellular level increase rate related to: nucleus accumbens

Type (Pharmacological Data)

dopamine extracellular level increase rate

Value of Type (Pharmacological Data)

235 percent

Kehr; Ichinose; Yoshitake; Goiny; Sievertsson; Nyberg; British Journal of Pharmacology; vol. 164; nb. 8; (2011); p. 1949 - 1958, View in Reaxys 39 of 373

Effect (Pharmacological Data)

neurotransmitter level; increase of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

17/242

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Route of Application

subcutaneous

Concentration (Pharmacological Data)

3 mg/kg

Kind of Dosing (Pharmacological Data)

comparative comp. dissolved in saline

Further Details (Pharmacological Data)

microdialysis; mass of species: 300 - 350 g; serotonin extracellular level increase rate related to: nucleus accumbens

Type (Pharmacological Data)

serotonin extracellular level increase rate

Value of Type (Pharmacological Data)

911 percent

Kehr; Ichinose; Yoshitake; Goiny; Sievertsson; Nyberg; British Journal of Pharmacology; vol. 164; nb. 8; (2011); p. 1949 - 1958, View in Reaxys 40 of 373

Effect (Pharmacological Data)

neurotransmitter metabolite level; decrease of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

3 mg/kg

Kind of Dosing (Pharmacological Data)

comparative comp. dissolved in saline

Further Details (Pharmacological Data)

microdialysis; DOPAC: 3,4-dihydroxyphenylacetic acid; 5-HIAA: 5-hydroxyindolacetic acid; mass of species: 300 - 350 g; 5-HIAA extracellular level decrease rate related to: nucleus accumbens

Type (Pharmacological Data)

5-HIAA extracellular level decrease rate

Value of Type (Pharmacological Data)

30.9 percent

Kehr; Ichinose; Yoshitake; Goiny; Sievertsson; Nyberg; British Journal of Pharmacology; vol. 164; nb. 8; (2011); p. 1949 - 1958, View in Reaxys 41 of 373

Effect (Pharmacological Data)

neurotransmitter metabolite level; decrease of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

3 mg/kg

Kind of Dosing (Pharmacological Data)

comparative comp. dissolved in saline

Further Details (Pharmacological Data)

microdialysis; DOPAC: 3,4-dihydroxyphenylacetic acid; 5-HIAA: 5-hydroxyindolacetic acid; mass of species: 300 - 350 g; DOPAC extracellular level decrease rate related to: nucleus accumbens

Type (Pharmacological Data)

DOPAC extracellular level decrease rate

Value of Type (Pharmacological Data)

27.6 percent

Kehr; Ichinose; Yoshitake; Goiny; Sievertsson; Nyberg; British Journal of Pharmacology; vol. 164; nb. 8; (2011); p. 1949 - 1958, View in Reaxys

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42 of 373

Effect (Pharmacological Data)

apoptosis; induction of

Species or Test-System (Pharmacological Data)

Wistar albino rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

20 mg/kg

Further Details (Pharmacological Data)

TUNEL assay; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labelling; mass of species: 200 - 250 g; apoptosis rate related to: hepatocytes

Type (Pharmacological Data)

apoptosis rate

Value of Type (Pharmacological Data)

38 percent

Cerretani; Bello; Cantatore; Fiaschi; Montefrancesco; Neri; Pomara; Riezzo; Fiore; Bonsignore; Turillazzi; Fineschi; Pharmacological Research; vol. 64; nb. 5; (2011); p. 517 - 527, View in Reaxys 43 of 373

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

Wistar albino rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

20 mg/kg

Further Details (Pharmacological Data)

mass of species: 200 - 250 g

Metabolite XRN (Pharmacological Data)

150196

Metabolite (Pharmacological Data)

3,4-methylenedioxyamphetamine

Effect (Pharmacological Data)

enzyme activity; decrease of

Species or Test-System (Pharmacological Data)

Wistar albino rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

20 mg/kg

Further Details (Pharmacological Data)

mass of species: 200 - 250 g; decrease rate related to: liver glutathione peroxidase

Type (Pharmacological Data)

decrease rate

Value of Type (Pharmacological Data)

25 percent

Effect (Pharmacological Data)

enzyme activity; decrease of

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Species or Test-System (Pharmacological Data)

Wistar albino rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

20 mg/kg

Further Details (Pharmacological Data)

mass of species: 200 - 250 g; decrease rate related to: liver glutathione reductase

Type (Pharmacological Data)

decrease rate

Value of Type (Pharmacological Data)

29 percent

Effect (Pharmacological Data)

oxidative stress; induction of

Species or Test-System (Pharmacological Data)

Wistar albino rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

20 mg/kg

Further Details (Pharmacological Data)

MDA: malondialdehyde; AA: ascorbic acid; GSH: glutathione reduced; GSSG: glutathione oxidized; mass of species: 200 - 250 g; AA concentration increase rate related to: liver

Type (Pharmacological Data)

AA concentration increase rate

Value of Type (Pharmacological Data)

32 percent

Effect (Pharmacological Data)

oxidative stress; induction of

Species or Test-System (Pharmacological Data)

Wistar albino rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

20 mg/kg

Further Details (Pharmacological Data)

MDA: malondialdehyde; AA: ascorbic acid; GSH: glutathione reduced; GSSG: glutathione oxidized; mass of species: 200 - 250 g; GSH/GSSG ratio decrease rate related to: liver

Type (Pharmacological Data)

GSH/GSSG ratio decrease rate

Value of Type (Pharmacological Data)

32 percent

Effect (Pharmacological Data)

oxidative stress; induction of

Species or Test-System (Pharmacological Data)

Wistar albino rat

Sex

male

20/242

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Route of Application

intraperitoneal

Concentration (Pharmacological Data)

20 mg/kg

Further Details (Pharmacological Data)

MDA: malondialdehyde; AA: ascorbic acid; GSH: glutathione reduced; GSSG: glutathione oxidized; mass of species: 200 - 250 g; MDA concentration increase rate related to: liver

Type (Pharmacological Data)

MDA concentration increase rate

Value of Type (Pharmacological Data)

119 percent

Effect (Pharmacological Data)

cytotoxic

Species or Test-System (Pharmacological Data)

embryonic kidney HEK293 cells of human

Concentration (Pharmacological Data)

1 μmol/l - 1 mmol/l

Further Details (Pharmacological Data)

effective concentration (EC)

Type (Pharmacological Data)

log EC50

Value of Type (Pharmacological Data)

-3.61

Cloonan, Suzanne M.; Keating, John J.; Corrigan, Desmond; O'Brien, John E.; Kavanagh, Pierce V.; Williams, D. Clive; Meegan, Mary J.; Bioorganic and Medicinal Chemistry; vol. 18; nb. 11; (2010); p. 4009 - 4031, View in Reaxys 50 of 373

Effect (Pharmacological Data)

cytotoxic

Species or Test-System (Pharmacological Data)

embryonic kidney HEK293 cells of human; genetically modified/infected with: human noradrenaline reuptake transporter

Concentration (Pharmacological Data)

1 μmol/l - 1 mmol/l

Further Details (Pharmacological Data)

effective concentration (EC)

Type (Pharmacological Data)

log EC50

Value of Type (Pharmacological Data)

-2.81

Effect (Pharmacological Data)

cytotoxic

Species or Test-System (Pharmacological Data)

embryonic kidney HEK293 cells of human; genetically modified/infected with: human dopamine reuptake transporter

Concentration (Pharmacological Data)

1 μmol/l - 1 mmol/l

Further Details (Pharmacological Data)

effective concentration (EC)

Type (Pharmacological Data)

log EC50

Value of Type (Pharmacological Data)

-2.71

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Effect (Pharmacological Data)

cytotoxic

Species or Test-System (Pharmacological Data)

metastatic bone neuroblastoma derived SHSY-5Y cells of human

Concentration (Pharmacological Data)

1 μmol/l - 1 mmol/l

Further Details (Pharmacological Data)

effective concentration (EC)

Type (Pharmacological Data)

log EC50

Value of Type (Pharmacological Data)

> -2

Effect (Pharmacological Data)

cytotoxic

Species or Test-System (Pharmacological Data)

embryonic kidney HEK293 cells of human; genetically modified/infected with: human serotonin reuptake transporter

Concentration (Pharmacological Data)

1 μmol/l - 1 mmol/l

Further Details (Pharmacological Data)

effective concentration (EC)

Type (Pharmacological Data)

log EC50

Value of Type (Pharmacological Data)

-3.31

Effect (Pharmacological Data)

noradrenaline concentration; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

150 mg/kg

Further Details (Pharmacological Data)

5-HT: serotonin; HPLC; mass of species: 200 - 250 g

Results

no effect (related to brain hypothalamus)

Vanattou-Saifoudine; McNamara; Harkin; British Journal of Pharmacology; vol. 160; nb. 4; (2010); p. 860 - 877, View in Reaxys 55 of 373

Effect (Pharmacological Data)

noradrenaline concentration; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

22/242

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Concentration (Pharmacological Data)

150 mg/kg

Further Details (Pharmacological Data)

5-HT: serotonin; HPLC; mass of species: 200 - 250 g

Results

no effect (related to brain cortex)

Vanattou-Saifoudine; McNamara; Harkin; British Journal of Pharmacology; vol. 160; nb. 4; (2010); p. 860 - 877, View in Reaxys 56 of 373

Effect (Pharmacological Data)

paraxanthine concentration; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

150 mg/kg

Further Details (Pharmacological Data)

mass of species: 200 - 250 g

Results

no effect (related to brain)

Vanattou-Saifoudine; McNamara; Harkin; British Journal of Pharmacology; vol. 160; nb. 4; (2010); p. 860 - 877, View in Reaxys 57 of 373

Effect (Pharmacological Data)

theophylline concentration; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

150 mg/kg

Further Details (Pharmacological Data)

mass of species: 200 - 250 g

Results

no effect (related to brain)

Vanattou-Saifoudine; McNamara; Harkin; British Journal of Pharmacology; vol. 160; nb. 4; (2010); p. 860 - 877, View in Reaxys 58 of 373

Effect (Pharmacological Data)

theobromine concentration; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

150 mg/kg

Further Details (Pharmacological Data)

mass of species: 200 - 250 g

Results

no effect (related to brain)

Vanattou-Saifoudine; McNamara; Harkin; British Journal of Pharmacology; vol. 160; nb. 4; (2010); p. 860 - 877, View in Reaxys 59 of 373

Effect (Pharmacological Data)

dopamine concentration; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

23/242

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Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

150 mg/kg

Further Details (Pharmacological Data)

5-HT: serotonin; HPLC; mass of species: 200 - 250 g

Results

no effect (related to brain hypothalamus)

Vanattou-Saifoudine; McNamara; Harkin; British Journal of Pharmacology; vol. 160; nb. 4; (2010); p. 860 - 877, View in Reaxys 60 of 373

Effect (Pharmacological Data)

dopamine concentration; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

150 mg/kg

Further Details (Pharmacological Data)

5-HT: serotonin; HPLC; mass of species: 200 - 250 g

Results

no effect (related to brain cortex)

Vanattou-Saifoudine; McNamara; Harkin; British Journal of Pharmacology; vol. 160; nb. 4; (2010); p. 860 - 877, View in Reaxys 61 of 373

Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

15 mg/kg

Further Details (Pharmacological Data)

mass of species: 200 - 250 g; maximal concentration related to: brain

Type (Pharmacological Data)

maximal concentration

Value of Type (Pharmacological Data)

12 ng/mg

Vanattou-Saifoudine; McNamara; Harkin; British Journal of Pharmacology; vol. 160; nb. 4; (2010); p. 860 - 877, View in Reaxys 62 of 373

Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

15 mg/kg

Further Details (Pharmacological Data)

mass of species: 200 - 250 g; time to Cmax related to: brain

Type (Pharmacological Data)

time to Cmax

24/242

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Value of Type (Pharmacological Data)

30 min

Vanattou-Saifoudine; McNamara; Harkin; British Journal of Pharmacology; vol. 160; nb. 4; (2010); p. 860 - 877, View in Reaxys 63 of 373

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

15 mg/kg

Further Details (Pharmacological Data)

mass of species: 200 - 250 g

Metabolite XRN (Pharmacological Data)

150196

Metabolite (Pharmacological Data)

3,4-methylenedioxyamphetamine

Vanattou-Saifoudine; McNamara; Harkin; British Journal of Pharmacology; vol. 160; nb. 4; (2010); p. 860 - 877, View in Reaxys 64 of 373

Effect (Pharmacological Data)

phase I enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

liver microsomes of rat

Sex

male

Concentration (Pharmacological Data)

<= 10 mmol/l

Further Details (Pharmacological Data)

methoxyresorufin-O-deethylase assay; IC50 related to: CYP1A/2

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

2124 μmol/l

Antolino-Lobo, Irene; Meulenbelt, Jan; Nijmeijer, Sandra M.; Scherpenisse, Peter; Van Den Berg, Martin; Van Duursen, Majorie B. M.; Drug Metabolism and Disposition; vol. 38; nb. 7; (2010); p. 1105 - 1112, View in Reaxys 65 of 373

Effect (Pharmacological Data)

phase I enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

liver microsomes of rat

Sex

male

Concentration (Pharmacological Data)

<= 10 mmol/l

Further Details (Pharmacological Data)

7-benzyloxy-4-(trifluoromethyl)coumarin as substrate, 50 μmol/l; IC50 related to: CYP3A2

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

4.75 μmol/l

Effect (Pharmacological Data)

phase I enzyme activity; inhibition of

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Species or Test-System (Pharmacological Data)

liver microsomes of rat

Sex

male

Concentration (Pharmacological Data)

<= 10 mmol/l

Further Details (Pharmacological Data)

3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7-methoxy-4-methylcoumarin as substrate, 1.5 μmol/l; IC50 related to: CYP2D1

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

3.72 μmol/l

Effect (Pharmacological Data)

phase I enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

liver epithelial cells of human; genetically modified/infected with: CYP1A2

Concentration (Pharmacological Data)

<= 4 mmol/l

Further Details (Pharmacological Data)

phluorescence-based P450 assay; methoxyresorufin as substrate, 5 μmol/l; IC50 related to: CYP1A2

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

822 μmol/l

Effect (Pharmacological Data)

phase I enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

liver epithelial cells of human; genetically modified/infected with: CYP1A2

Concentration (Pharmacological Data)

<= 4 mmol/l

Further Details (Pharmacological Data)

phluorescence-based P450 assay; methoxyresorufin as substrate, 5 μmol/l; maximal inhibitory rate related to: CYP1A2

Type (Pharmacological Data)

maximal inhibitory rate

Value of Type (Pharmacological Data)

76 percent

Effect (Pharmacological Data)

phase I enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

liver epithelial cells of human; genetically modified/infected with: CYP3A4

Concentration (Pharmacological Data)

<= 4 mmol/l

Further Details (Pharmacological Data)

phluorescence-based P450 assay; 7-benzyloxy-4-(trifluoromethyl)coumarin as substrate, 50 μmol/l; IC50 related to: CYP3A4

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

233 μmol/l

26/242

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Effect (Pharmacological Data)

phase I enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

liver epithelial cells of human; genetically modified/infected with: CYP3A4

Concentration (Pharmacological Data)

<= 4 mmol/l

Further Details (Pharmacological Data)

phluorescence-based P450 assay; 7-benzyloxy-4-(trifluoromethyl)coumarin as substrate, 50 μmol/l; maximal inhibitory rate related to: CYP3A4

Type (Pharmacological Data)

maximal inhibitory rate

Value of Type (Pharmacological Data)

100 percent

Effect (Pharmacological Data)

phase I enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

liver epithelial cells of human; genetically modified/infected with: CYP2D6

Concentration (Pharmacological Data)

<= 4 mmol/l

Further Details (Pharmacological Data)

phluorescence-based P450 assay; 3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7-methoxy-4-methylcoumarin as substrate, 100 μmol/l; IC50 related to: CYP2D6

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

75.6 μmol/l

Effect (Pharmacological Data)

phase I enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

liver epithelial cells of human; genetically modified/infected with: CYP2D6

Concentration (Pharmacological Data)

<= 4 mmol/l

Further Details (Pharmacological Data)

phluorescence-based P450 assay; 3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7-methoxy-4-methylcoumarin as substrate, 100 μmol/l; maximal inhibitory rate related to: CYP2D6

Type (Pharmacological Data)

maximal inhibitory rate

Value of Type (Pharmacological Data)

100 percent

Effect (Pharmacological Data)

cytotoxic

Species or Test-System (Pharmacological Data)

liver epithelial cells of human

Concentration (Pharmacological Data)

<= 10 mmol/l

Further Details (Pharmacological Data)

MTT assay

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Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

3.8 mmol/l

Effect (Pharmacological Data)

cytotoxic

Species or Test-System (Pharmacological Data)

liver epithelial cells of human

Concentration (Pharmacological Data)

<= 10 mmol/l

Further Details (Pharmacological Data)

MTT assay

Type (Pharmacological Data)

maximal cell death after 24 h

Value of Type (Pharmacological Data)

61.2 percent

Effect (Pharmacological Data)

cytotoxic

Species or Test-System (Pharmacological Data)

liver epithelial cells of human; genetically modified/infected with: CYP1A2

Further Details (Pharmacological Data)

MTT assay

Type (Pharmacological Data)

minimal effective concentration

Value of Type (Pharmacological Data)

3 mmol/l

Effect (Pharmacological Data)

cytotoxic

Species or Test-System (Pharmacological Data)

liver epithelial cells of human; genetically modified/infected with: CYP1A2

Further Details (Pharmacological Data)

MTT assay

Type (Pharmacological Data)

maximal cell death

Value of Type (Pharmacological Data)

14.4 percent

Effect (Pharmacological Data)

cytotoxic

Species or Test-System (Pharmacological Data)

liver epithelial cells of human; genetically modified/infected with: CYP2D6

Further Details (Pharmacological Data)

MTT assay

Type (Pharmacological Data)

effective concentration

28/242

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Value of Type (Pharmacological Data)

2 - 4 mmol/l

Effect (Pharmacological Data)

cytotoxic

Species or Test-System (Pharmacological Data)

liver epithelial cells of human; genetically modified/infected with: CYP2D6

Further Details (Pharmacological Data)

MTT assay

Type (Pharmacological Data)

maximal cell death rate

Value of Type (Pharmacological Data)

17.1 - 25.3 percent

Effect (Pharmacological Data)

cytotoxic

Species or Test-System (Pharmacological Data)

liver epithelial cells of human; genetically modified/infected with: CYP3A4

Further Details (Pharmacological Data)

MTT assay

Type (Pharmacological Data)

maximal cell death rate

Value of Type (Pharmacological Data)

61.9 percent

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

liver epithelial cells of human; genetically modified/infected with: CYP1A2

Concentration (Pharmacological Data)

1 mmol/l

Further Details (Pharmacological Data)

liquid chromatography/tandem mass spectrometry assay

Metabolite XRN (Pharmacological Data)

150196

Metabolite (Pharmacological Data)

3,4-methylenedioxyamphetamine

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

liver epithelial cells of human; genetically modified/infected with: CYP3A4

Concentration (Pharmacological Data)

1 mmol/l

Further Details (Pharmacological Data)

liquid chromatography/tandem mass spectrometry assay

Metabolite XRN (Pharmacological Data)

150196

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Metabolite (Pharmacological Data)

3,4-methylenedioxyamphetamine

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

liver epithelial cells of human; genetically modified/infected with: CYP2D6

Concentration (Pharmacological Data)

1 mmol/l

Further Details (Pharmacological Data)

liquid chromatography/tandem mass spectrometry assay

Metabolite XRN (Pharmacological Data)

150196; 9047579

Metabolite (Pharmacological Data)

3,4-methylenedioxyamphetamine; (+)-4-Hydroxy-3-methoxymethamphetamine

Effect (Pharmacological Data)

psychomotor activity; effect on

Species or Test-System (Pharmacological Data)

human

Sex

male and female

Route of Application

peroral

Concentration (Pharmacological Data)

25 - 100 mg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in bitter orange peel syrup and administered as single dose

Further Details (Pharmacological Data)

recreational title comp. users tested (mean lifetime title comp. use: 27 times)

Results

no effect; insignificant effect(s) discussed

Bosker, Wendy M.; Kuypers, Kim P. C.; Conen, Silke; Ramaekers, Johannes G.; Psychopharmacology; vol. 209; nb. 1; (2010); p. 69 - 76, View in Reaxys 84 of 373

Effect (Pharmacological Data)

sleep quality and quantity; effect on

Species or Test-System (Pharmacological Data)

human

Sex

male and female

Route of Application

peroral

Concentration (Pharmacological Data)

25 - 100 mg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in bitter orange peel syrup and administered as single dose

Further Details (Pharmacological Data)

recreational title comp. users tested (mean lifetime title comp. use: 27 times)

Results

no effect; insignificant effect(s) discussed

Bosker, Wendy M.; Kuypers, Kim P. C.; Conen, Silke; Ramaekers, Johannes G.; Psychopharmacology; vol. 209; nb. 1; (2010); p. 69 - 76, View in Reaxys 85 of 373

Effect (Pharmacological Data)

pharmacokinetics

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Species or Test-System (Pharmacological Data)

human

Sex

male and female

Route of Application

peroral

Concentration (Pharmacological Data)

25 - 100 mg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in bitter orange peel syrup and administered as single dose

Further Details (Pharmacological Data)

title comp. conc. measured 1.5 h after administration; concentration related to: serum

Type (Pharmacological Data)

concentration

Value of Type (Pharmacological Data)

25.8 - 157.2 ng/ml

Bosker, Wendy M.; Kuypers, Kim P. C.; Conen, Silke; Ramaekers, Johannes G.; Psychopharmacology; vol. 209; nb. 1; (2010); p. 69 - 76, View in Reaxys 86 of 373

Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

human

Sex

male and female

Route of Application

peroral

Concentration (Pharmacological Data)

25 - 100 mg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in bitter orange peel syrup and administered as single dose

Further Details (Pharmacological Data)

title comp. conc. measured 11.5 h after administration; concentration related to: serum

Type (Pharmacological Data)

concentration

Value of Type (Pharmacological Data)

14.2 - 84.3 ng/ml

Bosker, Wendy M.; Kuypers, Kim P. C.; Conen, Silke; Ramaekers, Johannes G.; Psychopharmacology; vol. 209; nb. 1; (2010); p. 69 - 76, View in Reaxys 87 of 373

Effect (Pharmacological Data)

protein binding affinity

Species or Test-System (Pharmacological Data)

embryonic kidney HEK-293 TRex cells of human; genetically modified/infected with: rat serotonin transporter

Concentration (Pharmacological Data)

1 - 100 μmol/l

Kind of Dosing (Pharmacological Data)

not clear from article whether title comp. or its hydrochloride used

Further Details (Pharmacological Data)

inhibitory concentration (IC)

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

1.06 μmol/l

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88 of 373

Effect (Pharmacological Data)

protein binding affinity

Species or Test-System (Pharmacological Data)

embryonic kidney HEK-293 TRex cells of human; genetically modified/infected with: rat serotonin transporter

Concentration (Pharmacological Data)

1 - 100 μmol/l

Kind of Dosing (Pharmacological Data)

not clear from article whether title comp. or its hydrochloride used

Results

molecular target: serotonin transporter

Effect (Pharmacological Data)

cytotoxic

Species or Test-System (Pharmacological Data)

embryonic kidney HEK-293 cells of human

Further Details (Pharmacological Data)

effective concentration (EC)

Type (Pharmacological Data)

log EC50

Value of Type (Pharmacological Data)

-3.61

Effect (Pharmacological Data)

cytotoxic

Species or Test-System (Pharmacological Data)

embryonic kidney HEK-293 cells of human; genetically modified/infected with: human serotonin transporter

Further Details (Pharmacological Data)

effective concentration (EC)

Type (Pharmacological Data)

log EC50

Value of Type (Pharmacological Data)

-3.31

Effect (Pharmacological Data)

cytotoxic

Species or Test-System (Pharmacological Data)

neuroblastoma SH-SY5Y cells of human

Further Details (Pharmacological Data)

effective concentration (EC)

Type (Pharmacological Data)

log EC50

Value of Type (Pharmacological Data)

> -2

Effect (Pharmacological Data)

cytotoxic

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Species or Test-System (Pharmacological Data)

Burkitt's lymphoma DG-75 cells of human

Further Details (Pharmacological Data)

effective concentration (EC)

Type (Pharmacological Data)

log EC50

Value of Type (Pharmacological Data)

-4.49

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

four title comp. doses were injected with 12-h intervals

Method (Pharmacological Data)

title comp. was administered to freely moving rats with microdialysis probe positioned in striatum; microdialysis samples were collected every 30 min for 5 h after each title comp. dose; 2,5-bis-(glutathion-S-yl)-N-Me-α-MeDA was measured with HPLC-CEAS

Further Details (Pharmacological Data)

control: saline; N-Me-α-MeDA: N-methyl-α-methyldopamine; HPLC-CEAS: high-performance liquid chromatography-coulometric electrode array system; AUC: area under curve

Half-life Time (Pharmacological Data)

82 - 104 min

Results

Cmax and Tmax of 2,5-bis-(glutathion-S-yl)-N-Me-α-MeDA did not change with repeated dosing and varied from 29 to 40 pmol/10 μl dialysate and 60 to 63 min, resp.; AUC0-300min decreased from 287 to 560 pmol/μl*min for 1st and 4th dose, resp.

Metabolite XRN (Pharmacological Data)

11296084

Metabolite (Pharmacological Data)

2,5-bis-(glutathion-S-yl)-N-methyl-α-methyldopamine

Erives, Gladys V.; Lau, Serrine S.; Monks, Terrence J.; Journal of Pharmacology and Experimental Therapeutics; vol. 324; nb. 1; (2008); p. 284 - 291, View in Reaxys 94 of 373

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

four title comp. doses were injected with 12-h intervals

Method (Pharmacological Data)

title comp. was administered to freely moving rats with microdialysis probe positioned in striatum; microdialysis samples were collected every 30 min for 5 h after each title comp. dose; 5-(N-acetylcystein-S-yl)-N-Me-α-MeDA was measured with HPLC-CEAS

Further Details (Pharmacological Data)

control: saline; N-Me-α-MeDA: N-methyl-α-methyldopamine; HPLC-CEAS: high-performance liquid chromatography-coulometric electrode array system

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Half-life Time (Pharmacological Data)

159 - 243 min

Results

5-(N-acetylcystein-S-yl)-N-Me-α-MeDA was not eliminated during 12-h interdose interval; time to 1/2 Cmax decreased with repeated dosing from 124 to 68 min and t1/2 increased; Tmax did not change with repeated dosing and varied from 167 to 217 min

Metabolite XRN (Pharmacological Data)

10025755

Metabolite (Pharmacological Data)

5-(N-acetylcystein-S-yl)-N-methyl-α-methyldopamine

Erives, Gladys V.; Lau, Serrine S.; Monks, Terrence J.; Journal of Pharmacology and Experimental Therapeutics; vol. 324; nb. 1; (2008); p. 284 - 291, View in Reaxys 95 of 373

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

four title comp. doses were injected with 12-h intervals

Method (Pharmacological Data)

title comp. was administered to freely moving rats with microdialysis probe positioned in striatum; microdialysis samples were collected every 30 min for 5 h after each dose; 2,5bis-(N-acetylcystein-S-yl)-N-Me-α-MeDA was measured with HPLC-CEAS

Further Details (Pharmacological Data)

control: saline; N-Me-α-MeDA: N-methyl-α-methyldopamine; HPLC-CEAS: high-performance liquid chromatography-coulometric electrode array system

Half-life Time (Pharmacological Data)

293 - 375 min

Results

2,5-bis-(N-acetylcystein-S-yl)-N-Me-α-MeDA was not eliminated during 12-h interdose interval; time to 1/2 Cmax decreased with repeated dosing from 85 to 17.5 min and t1/2 increased, while Tmax did not change and varied from 143 to 180 min

Metabolite XRN (Pharmacological Data)

11296085

Metabolite (Pharmacological Data)

2,5-bis-(N-acetylcystein-S-yl)-N-methyl-α-methyldopamine

Erives, Gladys V.; Lau, Serrine S.; Monks, Terrence J.; Journal of Pharmacology and Experimental Therapeutics; vol. 324; nb. 1; (2008); p. 284 - 291, View in Reaxys 96 of 373

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

four title comp. doses were injected with 12-h intervals

Method (Pharmacological Data)

title comp. was administered to freely moving rats with microdialysis probe positioned in striatum; microdialysis samples were collected every 30 min for 5 h after each title comp. dose; 5-(N-acetylcystein-S-yl)-N-Me-α-MeDA was measured with HPLC-CEAS

Further Details (Pharmacological Data)

control: saline; N-Me-α-MeDA: N-methyl-α-methyldopamine; HPLC-CEAS: high-performance liquid chromatography-coulometric electrode array system; AUC: area under curve

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Results

5-(N-acetylcystein-S-yl)-N-Me-α-MeDA Cmax increased with repeated dosing from 38 to 42 pmol/10 μl dialysate for 1st and 4th dose, resp.; AUC0-300min increased from 648 pmol/ μl*min for 1st dose to 873 pmol/μl*min for 4th dose, resp.

Metabolite XRN (Pharmacological Data)

10025755

Metabolite (Pharmacological Data)

5-(N-acetylcystein-S-yl)-N-methyl-α-methyldopamine

Erives, Gladys V.; Lau, Serrine S.; Monks, Terrence J.; Journal of Pharmacology and Experimental Therapeutics; vol. 324; nb. 1; (2008); p. 284 - 291, View in Reaxys 97 of 373

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

four title comp. doses were injected with 12-h intervals

Method (Pharmacological Data)

title comp. was administered to freely moving rats with microdialysis probe positioned in striatum; microdialysis samples were collected every 30 min for 5 h after each injection; 2,5-bis-(N-acetylcystein-S-yl)-N-Me-α-MeDA was measured with HPLC-CEAS

Further Details (Pharmacological Data)

control: saline; N-Me-α-MeDA: N-methyl-α-methyldopamine; HPLC-CEAS: high-performance liquid chromatography-coulometric electrode array system; AUC: area under curve

Results

2,5-bis-(N-acetylcystein-S-yl)-N-Me-α-MeDA Cmax increased with repeated dosing from 36 to 53 pmol/10 μl dialysate for 1st and 4th dose, resp.; AUC0-300min increased from 687 pmol/μl*min for 1st dose to 1273 pmol/μl*min for 4th dose, resp.

Metabolite XRN (Pharmacological Data)

11296085

Metabolite (Pharmacological Data)

2,5-bis-(N-acetylcystein-S-yl)-N-methyl-α-methyldopamine

Erives, Gladys V.; Lau, Serrine S.; Monks, Terrence J.; Journal of Pharmacology and Experimental Therapeutics; vol. 324; nb. 1; (2008); p. 284 - 291, View in Reaxys 98 of 373

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

four title comp. doses were injected with 12-h intervals

Method (Pharmacological Data)

title comp. was administered to freely moving rats with microdialysis probe positioned in striatum; microdialysis samples were collected every 30 min for 5 h after each title comp. dose; title comp. thioether metabolites were measured with HPLC-CEAS

Further Details (Pharmacological Data)

control: saline; N-Me-α-MeDA: N-methyl-α-methyldopamine; HPLC-CEAS: high-performance liquid chromatography-coulometric electrode array system; AUC: area under curve

Results

combined 5-(N-acetylcystein-S-yl)-N-Me-α-MeDA and 2,5-bis-(N-acetylcystein-S-yl)-NMe-α-MeDA concentration was nearly constant during 4 h after dosing and reached up to 130 pmol/10 μl dialysate; AUC0-300min increased 63percent between 1st and 4th doses

Metabolite XRN (Pharmacological Data)

10025755; 11296085

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Metabolite (Pharmacological Data)

5-(N-acetylcystein-S-yl)-N-methyl-α-methyldopamine; 2,5-bis-(N-acetylcystein-S-yl)-Nmethyl-α-methyldopamine

Erives, Gladys V.; Lau, Serrine S.; Monks, Terrence J.; Journal of Pharmacology and Experimental Therapeutics; vol. 324; nb. 1; (2008); p. 284 - 291, View in Reaxys 99 of 373

Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

four title comp. doses were injected with 12-h intervals

Method (Pharmacological Data)

5-HT and 5-HIAA concentrations were determined in striatum and cortex 7 days after the last title comp. dose using microdialysis technique and analysis with high-performance liquid chromatography-coulometric electrode array system

Further Details (Pharmacological Data)

control: saline; 5-HT: serotonin; 5-HIAA: 5-hydroxyindole acetic acid

Results

title comp. was toxic to serotonergic neurons, as shown by 66percent and 45percent decrease of 5-HT concentrations in striatum and cortex, resp., and 54percent and 39percent decrease of 5-HIAA concentrations in striatum and cortex, resp.

Erives, Gladys V.; Lau, Serrine S.; Monks, Terrence J.; Journal of Pharmacology and Experimental Therapeutics; vol. 324; nb. 1; (2008); p. 284 - 291, View in Reaxys 100 of 373 Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

four title comp. doses were injected with 12-h intervals

Method (Pharmacological Data)

title comp. was administered to freely moving rats with microdialysis probe positioned in striatum; microdialysis samples were collected every 30 min for 5 h after each title comp. dose and analyzed for 5-HT with HPLC-coulometric electrode array system

Further Details (Pharmacological Data)

control: saline; HPLC: high-performance liquid chromatography; 5-HT: serotonin; AUC: area under curve

Results

title comp. induced 5-HT release in striatum; release was maximal during 30 min after dosing and declined to control levels at 210 - 240 min; effect became weaker during repeated dosing and AUC0-300min decreased 42percent between first and fourth doses

Erives, Gladys V.; Lau, Serrine S.; Monks, Terrence J.; Journal of Pharmacology and Experimental Therapeutics; vol. 324; nb. 1; (2008); p. 284 - 291, View in Reaxys 101 of 373 Effect (Pharmacological Data)

cytochrome P450 enzyme isoform CYP2D6; inhibition of

Species or Test-System (Pharmacological Data)

cytochrome P450 enzyme isoform CYP2D6 of human

Method (Pharmacological Data)

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cent acetonitrile- water, 120 microliter).[00227] Solution A was transferred to a 96-well black plate (80 microliter per well), followed by various concentrations of a solution of Nmethyl-l-[3,4-methylenedioxyphenyl]- 2-aminopropane in 20percent acetonitrile-water (20 microliter per well). The reaction was initiated by adding 100 microliter of solution B to each well of the 96-well plate. The plate was incubated for 30 minutes at 37 0C in the dark. The reaction was stopped by adding 75 microliter of stop buffer (4:1 acetonitrile-0.5 M Tris base) to each well, and the end point was measured in a fluorometer plate reader at λeX = 409 nm and λc, = 460 run. Tranylcypromine was used as positive control (IC50 2.4 micromolar). Non-isotopically enriched N-methyl-1- [3,4-methylenedioxyphenyl]-2-aminopropane has an IC50 of 3 micromolar in this assay.[00228] It has thus been found that the inhibition concentration of CYP2D6 by compound of example 5 (d2-N-methyl-l-(3,4methylenedioxyphenyl)-2-aminopropane) is 8 micromolar, the inhibition concentration of CYP2D6 by compound of example 6 (ds-N- methyl-l-(3,4-methylenedioxyphenyl)-2-aminopropane) is 8 micromolar, and the inhibition concentration of CYP2D6 by compound of example 9 (d7-N-methyl-l- (3,4- methylenedioxyphenyl)-2-aminopropane) is 30 micromolar, indicating that these compounds inhibit CYP2D6 to a lesser degree as compared to the non-isotopically enriched N-methyl-1- [3,4-methylenedioxyphenyl]-2-aminopropane. Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

3 μmol/l

Location

Page/Page column 63-64

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys 102 of 373 Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

3 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. (purity >98percent) stock solution prepared in methanol and diluted with distilled water

Method (Pharmacological Data)

rats (7 weeks old, 215 g) administered with a single dose of title comp.; urine collected for 24 h in a vessel; analyzed by HPLC-ESI-MS in positive mode and selected-ion monitoring mode

Comment (Pharmacological Data)

Further metabolite(s)

Metabolite XRN (Pharmacological Data)

3261956; 150196; 15762976

Metabolite (Pharmacological Data)

4-Hydroxy-3-methoxymethamphetamine; 3,4-methylenedioxyamphetamine; 3-Hydroxy-4methoxymethamphetamine

Shima; Katagi; Kamata; Zaitsu; Nishikawa; Miki; Tsuchihashi; Sakuma; Nemoto; Xenobiotica; vol. 38; nb. 3; (2008); p. 314 - 324, View in Reaxys 103 of 373 Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in water

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Method (Pharmacological Data)

P-glycoprotein deficient mice (mdr1a (-/-)) administered with title comp.; killed at pre dose and post dose at 0.5 and 4 h; brain and plasma collected; title comp. conc. in brain and plasma determined by HPLC-FD

Further Details (Pharmacological Data)

control: normal mice administered with 10 ml/kg title comp.

Comment (Pharmacological Data)

No effect

Upreti, Vijay V.; Eddington, Natalie D.; Journal of Pharmaceutical Sciences; vol. 97; nb. 4; (2008); p. 1593 - 1605, View in Reaxys 104 of 373 Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

title comp dissolved in water

Method (Pharmacological Data)

rats (mdr1a (+/+)) pretreated with fluoxetine for 4 days and on d 4 administered with title comp.; killed at pre dose and post dose at 0.25-10 h; brain and plasma collected; title comp. conc. in brain and plasma determined by HPLC-FD

Further Details (Pharmacological Data)

control: mice administered with saline for 4 days and on d 4 administered with 10 ml/kg title comp.; fluoxetine dissolved in saline

Results

title comp. conc. in plasma and brain were higher at post dose 2 h in Fluoxetine treated mice than control; figure; table

Upreti, Vijay V.; Eddington, Natalie D.; Journal of Pharmaceutical Sciences; vol. 97; nb. 4; (2008); p. 1593 - 1605, View in Reaxys 105 of 373 Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

title comp dissolved in water

Method (Pharmacological Data)

rats (mdr1a (+/+)) pretreated with fluoxetine for 4 days and on d 4 administered with title comp.; killed at pre dose and post dose at 0.25-10 h; elimination half life in brain and plasma determined

Further Details (Pharmacological Data)

control: mice administered with saline for 4 days and on d 4 administered with 10 ml/kg title comp.; fluoxetine dissolved in saline

Half-life Time (Pharmacological Data)

2.1 - 4.9 h

Results

title comp. elimination half life increased by two-fold in plasma (from 2.4 to 4.9 h) and in brain (from 2.1 to 4.3 h); figure; table

Upreti, Vijay V.; Eddington, Natalie D.; Journal of Pharmaceutical Sciences; vol. 97; nb. 4; (2008); p. 1593 - 1605, View in Reaxys 106 of 373 Effect (Pharmacological Data) Species or Test-System (Pharmacological Data)

fatty acid level; increase of Sprague-Dawley rat

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Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

40 mg/kg

Method (Pharmacological Data)

blood samples obtained 30 and 60 min after title comp. administration via ventricular puncture for FFA analysis; plasma FFA levels determined by acyl-CoA synthetase-acylCoA oxidase method; nonesterified FFA measured by maximal absorption at 550 nm

Further Details (Pharmacological Data)

control: saline; FFA: free fatty acid

Results

title comp. sign. increased FFA plasma levels from 0.42 mEq/l (baseline value) to 0.93 mEq/l 30 min after administration (figure)

pyrogenic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

40 mg/kg

Method (Pharmacological Data)

body temperature measured 30 and 60 min after title comp. administration using Physiotem Thermalert TH-8 thermocouple attached to RET-2 rectal probe

Further Details (Pharmacological Data)

control: saline; internal control: baseline value

Results

title comp. sign. increased core body temperature to 40.43 deg C, a rise of 2.75 deg C over baseline value

pyrogenic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

40 mg/kg

Method (Pharmacological Data)

body temperature measured in HYPER TX rats at 1, 2 and 3 h after title comp. administration using Physiotem Thermalert TH-8 thermocouple attached to RET-2 rectal probe

Further Details (Pharmacological Data)

control: saline; internal control: sham-operated rats; HYPER: hyperthyroid; hyperthyroidism produced by daily administration of 100 μg/kg s.c. levothyroxine for 7 d; TX: thyroparathyroidectomized

Results

title comp. sign. increased (by ca. 32percent) core body temperature (2.9 deg C) over baseline value in HYPER TX rats; HYPER TX rats quickly succumbed to lethal effects, and death preceded by rapid decrease in body temperature

hypothermic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

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Route of Application

subcutaneous

Concentration (Pharmacological Data)

40 mg/kg

Method (Pharmacological Data)

body temperature measured in HYPO TX rats at 1, 2 and 3 h after title comp. administration using Physiotem Thermalert TH-8 thermocouple attached to RET-2 rectal probe

Further Details (Pharmacological Data)

control: saline; internal control: sham-operated rats; HYPO: hypothyroid, rats without chronic thyroxine administration; further investigation with levothyroxine (30 min before title comp.); TX: thyroparathyroidectomized

Results

title comp. induced marked and lasting hypothermia (-3.6 deg C) compared to baseline value in HYPO TX rats; acute pretreatment with levothyroxine had no effect on title comp.induced temperature response (figure)

Effect (Pharmacological Data)

pyrogenic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

40 mg/kg

Method (Pharmacological Data)

body temperature measured in EU rats at 1, 2 and 3 h after title comp. administration using Physiotem Thermalert TH-8 thermocouple attached to RET-2 rectal probe

Further Details (Pharmacological Data)

control: saline; internal control: baseline value; EU: euthyroid; further investigation with levothyroxine (30 min before title comp. administration)

Results

title comp. administration led to sign. elevation in core body temperature in EU rats (2.1 deg C) that was sustained for 3 h; acute pretreatment with levothyroxine had no effect on title comp.-induced temperature response (figure)

Effect (Pharmacological Data)

protein expression; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

40 mg/kg

Method (Pharmacological Data)

180 min after title comp. administration to EU rats mitochondrial lysates from gastrocnemius muscle prepared; UCP3 expression assessed using Western blot analysis

Further Details (Pharmacological Data)

control: saline (7.5 μg/dl); internal control: UCP3-deficient mice; EU: euthyroid; UCP: uncoupling protein; further investigation with levothyroxine (30 min before title comp. administration)

Comment (Pharmacological Data)

No effect

Effect (Pharmacological Data)

protein expression; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

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Route of Application

subcutaneous

Concentration (Pharmacological Data)

40 mg/kg

Method (Pharmacological Data)

180 min after title comp. administration to TX HYPO rats mitochondrial lysates from gastrocnemius muscle prepared; using Western blot analysis

Further Details (Pharmacological Data)

control: saline; internal control: UCP3-/- mice; HYPO: hypothyroid; UCP: uncoupling protein; further investigation with levothyroxine (30 min before title comp. administration); TX: thyroparathyroidectomized

Comment (Pharmacological Data)

No effect

Effect (Pharmacological Data)

protein expression; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

40 mg/kg

Method (Pharmacological Data)

180 min after title comp. injection to TX HYPER rats mitochondrial lysates from gastrocnemius muscle prepared; UCP3 expression assessed using Western blot analysis

Further Details (Pharmacological Data)

control: saline (48.6 μg/dl); internal control: UCP3-/- mice; HYPER: hyperthyroid; hyperthyroidism induced by daily i.p. administration of 100 μg/kg levothyroxine for 7 d; GE: gel electrophoresis; UCP: uncoupling protein; TX: thyroparathyroidectomized

Comment (Pharmacological Data)

No effect

Effect (Pharmacological Data)

pyrogenic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Method (Pharmacological Data)

DCMB or saline given i.p. 60 min prior to title comp. treatment; body temperature measured up to 60 min after title comp. administration using Physiotem Thermalert TH-8 thermocouple attached to RET-2 rectal probe

Further Details (Pharmacological Data)

control: saline; internal control: baseline value; DCMB:+/-2,3-dichloro-α-methylbenzylamine, inhibitor of phenylethanolamine N-methyltransferase

Results

title comp. sign. increased core body temperature by ca. 3 deg C over baseline value; DCMB when combined with title comp. potentiated title comp.-induced hypothermic effect and led to increase of rectal temperature by ca. 4 deg C (figure)

Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

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Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Method (Pharmacological Data)

DCMB or saline given i.p. 60 min prior to title comp.; to evaluate NE and Epi plasma levels blood obtained at 30 and 60 min after title comp. injection; NE and Epi levels determined using HPLC with electrochemical detection

Further Details (Pharmacological Data)

control: baseline value (7.42 pg/μl); DCMB: +/-2,3-dichloro-α-methylbenzylamine, inhibitor of phenylethanolamine N-methyltransferase; HPLC: high-performance liquid chromatography; NE: norepinephrine; Epi: epinephrine

Results

title comp. sign. increased NE levels to 106.7 times of baseline after 60 min; combination of DCMB with title comp. enhanced plasma NE levels to 189.3 times of baseline 60 min after title comp. treatment (figure)

Effect (Pharmacological Data)

metabolism; inhibition of

Species or Test-System (Pharmacological Data)

human Supersomes with human CYP2D6 content

Kind of Dosing (Pharmacological Data)

used at doses of 0.5*Km, Km and 2*Km; dissolved in incubate

Method (Pharmacological Data)

enzyme incubated with title comp. (no or 30-min preincubation) and methadone (as substrate at dose equal to its Km (2.98 μM)) for 20 min at 37 deg C, pH 7.4; EDDP det. by HPLC/tandem MS

Further Details (Pharmacological Data)

Km: Michaelis Menten constant for enzyme investigated; EDDP: 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine; control: without title comp.; Km for title comp.: 4.1 μM

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

1.46 μmol/l

Results

conversion of methadone at title comp. doses of 0.5*Km/Km/2*Km without and with preincubation: 39.3/21.7/14.2 and 76.4/22.9/13.8percent (ratio relative to control velocity), resp.; effect reversible

Bomsien, Stephanie; Skopp, Gisela; European Journal of Clinical Pharmacology; vol. 63; nb. 9; (2007); p. 821 827, View in Reaxys 117 of 373

Effect (Pharmacological Data)

transmitter release; inhibition of

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 mg/kg

Kind of Dosing (Pharmacological Data)

used as hydrochloride; solution in saline; administration 3 times at 2 h intervals

Method (Pharmacological Data)

treatment with title comp. alone or combined with amiloride (2.5 mg/kg i.p. 30 min before each title comp. dose); 7 d later 5-HT levels in frontal cortex, hippocampus, and striatum were determined with high performance liquid chromatography

Further Details (Pharmacological Data)

control: vehicle; further investigations with voltage-dependent Ca(2+) channel antagonists flunarizine and diltiazem, with 5-HT transporter inhibitor fluoxetine, and by lowering room temperature to 15 deg C; 5-HT: 5-hydroxytryptamine

Results

title comp. reduced 5-HT level in brain more potently in combination with amiloride than alone; effect of title comp. with/without amiloride was reduced or prevented by fluoxetine and low temp., but was mostly not affected by fluoxetine and diltiazem

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Goni-Allo, Beatriz; Puerta, Elena; Hervias, Isabel; Di Palma, Richard; Ramos, Maria; Lasheras, Berta; Aguirre, Norberto; European Journal of Pharmacology; vol. 562; nb. 3; (2007); p. 198 - 207, View in Reaxys 118 of 373

Effect (Pharmacological Data)

transmitter release; inhibition of

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 mg/kg

Kind of Dosing (Pharmacological Data)

used as hydrochloride; solution in saline; administration 3 times at 2 h intervals

Method (Pharmacological Data)

treatment with title comp. alone or combined with amiloride (2.5 mg/kg i.p. 30 min before each title comp. dose); 7 d later 5-HIAA levels in frontal cortex, hippocampus, and striatum were determined with high performance liquid chromatography

Further Details (Pharmacological Data)

Results

title comp. reduced 5-HIAA level more potently in combination with amiloride than alone; this effect was prevented by fluoxetine and reduced by flunarizine, but not low temp. or diltiazem; effect potentiation by amiloride was prevented by low temp.

Effect (Pharmacological Data)

pyrogenic

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 mg/kg

Kind of Dosing (Pharmacological Data)

used as hydrochloride; solution in saline; administration 3 times at 2 h intervals

Method (Pharmacological Data)

treatment with title comp. alone or combined with amiloride (2.5 mg/kg i.p. 30 min before each title comp. dose); core body temp. was monitored from 30 min before to 8 h after the first title comp. dose; area under curve was calculated

Further Details (Pharmacological Data)

Results

title comp. increased body temp. more potently in combination with amiloride than alone; this effect was not changed by fluoxetine, flunarizine, or diltiazem, but was completely prevented by low room temp.

transmitter release; inhibition of

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 mg/kg

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Kind of Dosing (Pharmacological Data)

used as hydrochloride; solution in saline; administration 3 times at 2 h intervals

Method (Pharmacological Data)

treatment with title comp. alone or combined with dimethylamiloride (2.5 mg/kg i.p. 30 min before each title comp. dose); 7 d later 5-HT and 5-HIAA in frontal cortex, hippocampus, and striatum were measured with high performance liquid chromatography

Further Details (Pharmacological Data)

control: vehicle; further investigations with 5-HT transporter inhibitor fluoxetine; 5-HT: 5hydroxytryptamine; 5-HIAA: 5-hydroxyindole acetic acid

Results

title comp. reduced 5-HT and 5-HIAA levels in brain more potently in combination with dimethylamiloride than alone; effect of title comp. with or without dimethylamiloride was completely prevented by fluoxetine

pyrogenic

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 mg/kg

Kind of Dosing (Pharmacological Data)

used as hydrochloride; solution in saline; administration 3 times at 2 h intervals

Method (Pharmacological Data)

treatment with title comp. alone or combined with dimethylamiloride (2.5 mg/kg i.p. 30 min before each title comp. dose); core body temp. was monitored from 30 min before to 8 h after the first title comp. dose; area under curve was calculated

Further Details (Pharmacological Data)

control: vehicle; further investigations with 5-HT transporter inhibitor fluoxetine

Results

title comp. increased body temp. more potently in combination with dimethylamiloride than alone; this effect was not changed by fluoxetine

transmitter release; effect on

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 mg/kg

Kind of Dosing (Pharmacological Data)

used as hydrochloride; solution in saline; administration 3 times at 2 h intervals

Method (Pharmacological Data)

treatment with title comp. alone or combined with amiloride or dimethylamiloride (2.5 mg/kg i.p. 30 min before each title comp. dose); 7 d later dopamine, DOPAC, and homovanillic acid were measured in striatum with high-performance liquid chromatography

Further Details (Pharmacological Data)

control: vehicle; further investigations with voltage-dependent Ca(2+) channel antagonists flunarizine and diltiazem and with 5-HT transporter inhibitor fluoxetine; DOPAC: dihydroxyphenylacetic acid

Comment (Pharmacological Data)

No effect

transmitter release; inhibition of

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Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Kind of Dosing (Pharmacological Data)

used as hydrochloride; solution in artificial cerebrospinal fluid; administration into striatum using reverse dialysis at 100 μmol/l, 2 μl/min, during 8 h

Method (Pharmacological Data)

treatment with title comp. alone or combined with amiloride (2.5 mg/kg i.p., 3 times every 2 h starting 30 min before title comp.); 7 d later 5-hydroxytryptamine (5-HT) level in striatum was determined with high-performance liquid chromatography

Further Details (Pharmacological Data)

experiment was performed in normothermic rats or in rats heated to 39.45 deg C during the first 5 h of treatment; control: vehicle

Results

title comp. plus amiloride reduced 5-HT level in hyperthermic rats; no effect for title comp. alone; no effect in normothermic rats

body temperature; effect on

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Kind of Dosing (Pharmacological Data)

used as hydrochloride; solution in artificial cerebrospinal fluid; administration into striatum using reverse dialysis at 100 μmol/l, 2 μl/min, during 8 h

Method (Pharmacological Data)

treatment with title comp. alone or combined with amiloride (2.5 mg/kg i.p., 3 times every 2 h starting 30 min before title comp.); core body temp. was monitored

Further Details (Pharmacological Data)

control: vehicle

Comment (Pharmacological Data)

No effect

monoamine re-uptake; inhibition of

Species or Test-System (Pharmacological Data)

brain crude striatum synaptosomes of Sprague-Dawley rat

Sex

male

Kind of Dosing (Pharmacological Data)

title comp. purity was 98.0percent

Method (Pharmacological Data)

synaptosomes incubated with title comp. for 10 min at 37 deg C before <3H>dopamine addition; 5 min at 37 deg C; scintillation counted

Further Details (Pharmacological Data)

non-specific uptake obtained in the presence of GBR12909; positive control: cocaine (IC50 = 8.5E-7 M) and methamphetamine (IC50 = 3.7E-7 M)

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

1.4E-6 mol/l

Results

title comp. strongly inhibited re-uptake of dopamine

Nagai, Fumiko; Nonaka, Ryouichi; Satoh Hisashi Kamimura, Kanako; European Journal of Pharmacology; vol. 559; nb. 2-3; (2007); p. 132 - 137, View in Reaxys 126 of 373 Effect (Pharmacological Data)

monoamine re-uptake; inhibition of

Species or Test-System (Pharmacological Data)

brain cortex synaptosomes of Sprague-Dawley rat

Sex

male

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Kind of Dosing (Pharmacological Data)

title comp. purity was 98.0percent

Method (Pharmacological Data)

synaptosomes incubated with title comp. for 10 min at 37 deg C before <3H>5-HT addition; 5 min at 37 deg C; scintillation counted

Further Details (Pharmacological Data)

non-specific uptake obtained in the presence of citalopram; positive control: cocaine (IC50 = 2.1E-6 M) and methamphetamine (IC50 = 4.0E-6 M); 5-HT: serotonin

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

7.2E-7 mol/l

Results

title comp. strongly inhibited re-uptake of 5-HT

Nagai, Fumiko; Nonaka, Ryouichi; Satoh Hisashi Kamimura, Kanako; European Journal of Pharmacology; vol. 559; nb. 2-3; (2007); p. 132 - 137, View in Reaxys 127 of 373 Effect (Pharmacological Data)

monoamine re-uptake; inhibition of

Species or Test-System (Pharmacological Data)

brain cortex synaptosomes of Sprague-Dawley rat

Sex

male

Kind of Dosing (Pharmacological Data)

title comp. purity was 98.0percent

Method (Pharmacological Data)

synaptosomes incubated with title comp. for 10 min at 37 deg C before <3H>norepinephrine addition; 5 min at 37 deg C; scintillation counted

Further Details (Pharmacological Data)

non-specific uptake obtained at 0 deg C; positive control: cocaine (IC50 = 3.4E-7 M) and methamphetamine (IC50 = 2.0E-7 M)

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

6.6E-7 mol/l

Results

title comp. strongly inhibited re-uptake of norepinephrine

Nagai, Fumiko; Nonaka, Ryouichi; Satoh Hisashi Kamimura, Kanako; European Journal of Pharmacology; vol. 559; nb. 2-3; (2007); p. 132 - 137, View in Reaxys 128 of 373 Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

brain crude striatum synaptosomes of Sprague-Dawley rat

Sex

male

Kind of Dosing (Pharmacological Data)

title comp. purity was 98.0percent

Method (Pharmacological Data)

synaptosomes pre-loaded with <3H>dopamine added to plate containing title comp.; 5 min at 25 deg C; scintillation counted

Further Details (Pharmacological Data)

non-displaceable tritium measured in the presence of tyramine; positive control: methamphetamine (EC50 = 2.80E-8 M); cocaine: no effect

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

2.0E-7 mol/l

Results

title comp. strongly stimulated release of dopamine

Nagai, Fumiko; Nonaka, Ryouichi; Satoh Hisashi Kamimura, Kanako; European Journal of Pharmacology; vol. 559; nb. 2-3; (2007); p. 132 - 137, View in Reaxys 129 of 373 Effect (Pharmacological Data)

transmitter releasing

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Species or Test-System (Pharmacological Data)

brain cortex synaptosomes of Sprague-Dawley rat

Sex

male

Kind of Dosing (Pharmacological Data)

title comp. purity was 98.0percent

Method (Pharmacological Data)

synaptosomes pre-loaded with <3H>5-HT added to plate containing title comp.; 30 min at 25 deg C; scintillation counted

Further Details (Pharmacological Data)

non-displaceable tritium measured in the presence of tyramine; positive control: methamphetamine (EC50 = 7.9E-7 M); cocaine: no effect; 5-HT: serotonin

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

5.8E-8 mol/l

Results

title comp. strongly stimulated release of 5-HT

Nagai, Fumiko; Nonaka, Ryouichi; Satoh Hisashi Kamimura, Kanako; European Journal of Pharmacology; vol. 559; nb. 2-3; (2007); p. 132 - 137, View in Reaxys 130 of 373 Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

brain cortex synaptosomes of Sprague-Dawley rat

Sex

male

Kind of Dosing (Pharmacological Data)

title comp. purity was 98.0percent

Method (Pharmacological Data)

synaptosomes pre-loaded with <3H>norepinephrine added to plate containing title comp.; 30 min at 25 deg C; scintillation counted

Further Details (Pharmacological Data)

non-displaceable tritium measured in the presence of tyramine; positive control: methamphetamine (EC50 = 1.1E-8 M); cocaine: no effect

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

8.6E-8 mol/l

Results

title comp. strongly stimulated release of norepinephrine

Nagai, Fumiko; Nonaka, Ryouichi; Satoh Hisashi Kamimura, Kanako; European Journal of Pharmacology; vol. 559; nb. 2-3; (2007); p. 132 - 137, View in Reaxys 131 of 373 Effect (Pharmacological Data)

cytokine production; inhibition of

Species or Test-System (Pharmacological Data)

CD-1 mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 - 20 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.89percent NaCl; 10 ml/kg

Method (Pharmacological Data)

8 h after treatment with title comp. and 100 μg/kg LPS IL-12 and IFN-γ conc. in serum determined by ELISA

Further Details (Pharmacological Data)

LPS: lipopolysaccharides from Escherichia coli serotype 0111:B4; IL: interleukin; IFN: interferon

Results

title comp. dose-dependently sign. reduced LPS-induced increase in IFN-γ and IL-12p40 conc. by ca. 100 and 50percent at highest conc., resp. (figure)

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Boyle, Noreen T.; Connor, Thomas J.; European Journal of Pharmacology; vol. 572; nb. 2-3; (2007); p. 228 - 238, View in Reaxys 132 of 373 Effect (Pharmacological Data)

gene expression; reduction of

Species or Test-System (Pharmacological Data)

CD-1 mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 - 20 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.89percent NaCl; 10 ml/kg

Method (Pharmacological Data)

8 h after treatment with title comp. and 100 μg/kg LPS amount of interleukin (IL)-12p40 and p35, interferon (IFN)-γ, IP-10, IL-15 and IL-18 mRNA in spleen determined by realtime-PCR

Further Details (Pharmacological Data)

LPS: lipopolysaccharides from Escherichia coli serotype 0111:B4; IP-10: IFN-γ-inducible protein 10; further invest. with anti-IL-10 receptor (Rs) antibodies (ab), peripherally acting β-adrenoceptor antagonist (nadolol)

Results

title comp. dose-dependently sign. reduced LPS-induced increase in IFN-γ, IP-10, IL-12p40 and IL-15 expression, and had no effect on IL-18 and IL-12p35; reducing effect blocked by anti-IL-10 Rs ab and nadolol (figures)

Boyle, Noreen T.; Connor, Thomas J.; European Journal of Pharmacology; vol. 572; nb. 2-3; (2007); p. 228 - 238, View in Reaxys 133 of 373 Effect (Pharmacological Data)

cytokine production; effect on

Species or Test-System (Pharmacological Data)

CD-1 mouse splenocytes

Sex

male

Concentration (Pharmacological Data)

1 - 50 μmol/l

Method (Pharmacological Data)

1 h after cell incubation with title comp. 1 μg/ml LPS added for 24-72 h; amount of interleukin (IL)-12p40 and interferon (IFN)-γ in supernatant determined by ELISA

Further Details (Pharmacological Data)

1-10 ng/ml IL-10 used for reference; LPS: lipopolysaccharides from Escherichia coli serotype 0111:B4

Comment (Pharmacological Data)

No effect

Boyle, Noreen T.; Connor, Thomas J.; European Journal of Pharmacology; vol. 572; nb. 2-3; (2007); p. 228 - 238, View in Reaxys 134 of 373 Effect (Pharmacological Data)

protein phosphorylation; inhibition of

Species or Test-System (Pharmacological Data)

CD-1 mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 - 20 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.89percent NaCl; 10 ml/kg

Method (Pharmacological Data)

8 h after treatment with title comp. and 100 μg/kg LPS STAT1 phosphorylation in spleen analyzed by Western blotting

Further Details (Pharmacological Data)

LPS: lipopolysaccharides from Escherichia coli serotype 0111:B4; STAT1: signal transducer and activator of transcription-1; further invest. with anti-IL-10 receptor (Rs) antibodies (ab), peripherally acting β-adrenoceptor antagonist (nadolol)

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Results

title comp. dose-dependently sign. reduced LPS-induced increase in STAT1 phosphorylation by ca. 2-fold at highest conc.; effect blocked by anti-IL-10 Rs ab and nadolol (figures)

Boyle, Noreen T.; Connor, Thomas J.; European Journal of Pharmacology; vol. 572; nb. 2-3; (2007); p. 228 - 238, View in Reaxys 135 of 373 Effect (Pharmacological Data)

cytokine production; induction of

Species or Test-System (Pharmacological Data)

CD-1 mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 - 20 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.89percent NaCl; 10 ml/kg

Method (Pharmacological Data)

2 h after treatment with title comp. and 100 μg/kg LPS IL-10 conc. in serum determined by ELISA

Further Details (Pharmacological Data)

LPS: lipopolysaccharides from Escherichia coli serotype 0111:B4; IL: interleukin; further invest. with peripherally acting β-adrenoceptor antagonist (nadolol)

Results

title comp. dose-dependently sign. increased LPS-induced IL-10 production by ca. 25-fold at highest conc.; effect blocked by nadolol (figures)

Boyle, Noreen T.; Connor, Thomas J.; European Journal of Pharmacology; vol. 572; nb. 2-3; (2007); p. 228 - 238, View in Reaxys 136 of 373 Effect (Pharmacological Data)

body temperature; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

1.5 - 15 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in saline

Method (Pharmacological Data)

animals were treated with title comp., body temperature was measured for 120 min

Further Details (Pharmacological Data)

control: vehicle

Results

7.5 mg/kg dose of title comp. induced a transient hypothermic response, temperature returned to baseline values at 80 min; 15 mg/kg dose elicited a purely hyperthermic response; fig.

Rusyniak, Daniel E.; Zaretskaia, Maria V.; Zaretsky, Dmitry V.; DiMicco, Joseph A.; Journal of Pharmacology and Experimental Therapeutics; vol. 323; nb. 2; (2007); p. 477 - 487, View in Reaxys 137 of 373 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

1.5 - 15 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in saline

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Method (Pharmacological Data)

animals were treated with title comp., the effect on motor activity was analyzed

Further Details (Pharmacological Data)

control: vehicle

Results

7.5 and 15 mg/kg doses of title comp. induced increases in motor activity; fig.

hypothermia; induction of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

7.5 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in saline

Method (Pharmacological Data)

animals were treated with title comp., the effect on body temperature was analyzed for 120 min

Further Details (Pharmacological Data)

control: vehicle; further investigation with 5-HT1A receptor antagonist (i.p. or injected into rostral raphe pallidus)

Results

title comp. induced a transient decrease in body temperature; 5-HT1A receptors were possibly involved, but they were not located in rostral raphe pallidus; fig.

behavioural symptoms

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

7.5 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in saline

Method (Pharmacological Data)

animals were treated with title comp., the effect on locomotor activity was analyzed for 120 min

Further Details (Pharmacological Data)

control: vehicle; further investigation with 5-HT1A receptor antagonist (i.p. or injected into the rostral raphe pallidus)

Results

title comp. increased locomotor activity, 5-HT1A receptors possibly involved, but they were not located in rostral raphe pallidus; fig.

chronotropic pos.

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

7.5 mg/kg

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Kind of Dosing (Pharmacological Data)

dissolved in saline

Method (Pharmacological Data)

animals were treated with title comp., the effect on heart rate was analyzed for 120 min

Further Details (Pharmacological Data)

control: vehicle; further investigation with 5-HT1A receptor antagonist (i.p. or injected into the rostral raphe pallidus)

Results

title comp. increased heart rate, 5-HT1A receptors located in the rostral raphe pallidus were possibly involved; fig.

arterial pressure; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

7.5 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in saline

Method (Pharmacological Data)

animals were treated with title comp., the effect on mean arterial pressure was analyzed for 120 min

Further Details (Pharmacological Data)

control: vehicle; further investigation with 5-HT1A receptor antagonist

Comment (Pharmacological Data)

No effect

drug interaction

Species or Test-System (Pharmacological Data)

human

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

100 mg

Method (Pharmacological Data)

subjects were treated with title comp.; physiological parameters (SBP, DBP, heart rate, oral temperature, pupil diameter) were assessed for 1-24 h

Further Details (Pharmacological Data)

placebo control; SBP: systolic blood pressure; DBP: diastolic blood pressure; further investigations using pretreatment with inhibitor of 5-hydroxytryptamine reuptake and CYP2D6, paroxetine

Results

title comp. increased physiological parameters; paroxetine reduced effect of title comp.; table, figure

Farre, Magi; Abanades, Sergio; Roset, Pere N.; Peiro, Ana M.; Torrens, Marta; O'Mathuna, Bryan; Segura, Mireia; De La Torre, Rafael; Journal of Pharmacology and Experimental Therapeutics; vol. 323; nb. 3; (2007); p. 954 - 962, View in Reaxys 143 of 373 Effect (Pharmacological Data)

drug interaction

Species or Test-System (Pharmacological Data)

human

Sex

male

Route of Application

peroral

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Concentration (Pharmacological Data)

100 mg

Method (Pharmacological Data)

subjects were treated with title comp.; psychomotor effects; digit symbol substitution test; simple reaction time; Pauli test; Maddox-wing device at 1-24 h

Further Details (Pharmacological Data)

placebo control; further investigations using pretreatment with inhibitor of 5-hydroxytryptamine reuptake and CYP2D6, paroxetine

Results

title comp. caused deterioration of psychomotor performance; paroxetine reduced effects of title comp.; table, figure

drug interaction

Species or Test-System (Pharmacological Data)

human

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

100 mg

Method (Pharmacological Data)

subjects were treated with title comp.; subjective effects; ARCI; VESSPA questionnaire and VAS at 1-24 h

Further Details (Pharmacological Data)

placebo control; VESSPA: Evaluation of Subjective Effects of Substances with Abuse Potential questionnaire; VAS: visual analog scales; ARCI: Addition Research Center Inventory; further investigations using pretreatment with paroxetine

Results

title comp. increased ARCI and VESSPA scales and VAS effects; paroxetine reduced effects of title comp.; table, figure

pharmacokinetics

Species or Test-System (Pharmacological Data)

human

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

100 mg

Method (Pharmacological Data)

treatment with title comp.; plasma concentrations of title comp. and HMMA were measured at 1-24 h; mass spectrometry

Further Details (Pharmacological Data)

placebo control; HMMA: 3-methoxy-4-hydroxymethamphetamine; further investigations using pretreatment with inhibitor of 5-hydroxytryptamine reuptake and CYP2D6, paroxetine

Half-life Time (Pharmacological Data)

7.88 h

Results

title comp.: Cmax=212.72 μg/l, Tmax=1.50 h, Ke=0.0903 h*E-1, AUC0-21=2115.26 μg/l/h; HMMA: Cmax=193.14, Tmax=2.25 h, Ke=0.0740 h*E-1, AUC0-21=1923.32, t1/2=9.54 h; paroxetine increased level of title comp. and decreased HMMA; table, figure

chronotropic neg.

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Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.9percent NaCl; administered in an injection volume of 1 ml/kg

Method (Pharmacological Data)

rats administered with title comp. alone or with caffeine; heart rate recorded by radiotelemetry; average computed at 5-min intervals for 1 h prior to and 4 h following title comp. administration

Further Details (Pharmacological Data)

control: vehicle

Results

title comp. reduced heart rate 20 min post-dose for 40 min; co-administration with caffeine attenuated title comp.-induced reduction in heart rate and provoked tachycardic response (1 h and 15 min post-dose), which persisted for duration of trial; fig.

McNamara, Ruth; Maginn, Mark; Harkin, Andrew; European Journal of Pharmacology; vol. 555; nb. 2-3; (2007); p. 194 - 198, View in Reaxys 147 of 373 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.9percent NaCl; administered in an injection volume of 1 ml/kg

Method (Pharmacological Data)

rats administered with title comp. alone or with caffeine; locomotor activity recorded by radiotelemetry; average computed at 5-min intervals for 1 h prior to and 4 h following title comp. administration

Further Details (Pharmacological Data)

control: vehicle

Results

title comp. induced an increase in locomotor output 30 min post-dose, which persisted until end of trial compared to control; co-administration with caffeine did not affect title comp.induced locomotor response compared to title comp. alone; fig.

McNamara, Ruth; Maginn, Mark; Harkin, Andrew; European Journal of Pharmacology; vol. 555; nb. 2-3; (2007); p. 194 - 198, View in Reaxys 148 of 373 Effect (Pharmacological Data)

cardiovascular

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat heart

Sex

male

Concentration (Pharmacological Data)

1 - 30 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. solution prepared by dissolving in Krebs-Henseleit buffer

Method (Pharmacological Data)

hearts perfused by Langendorff technique using Krebs-Henseleit solution; stimulated at 290 beats/min; equilibrated for 15 min; title comp. added alone or with caffeine; ECG and HR continuously monitored; P, QRS and T waves detected from ECG waveform

Further Details (Pharmacological Data)

control: vehicle; HR: heart rate

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Results

PQ and QRS interval showed no effect of title comp.; trend towards increase in QT interval was obsd. with 30 μmol/l title comp.; neither title comp. alone or in combination with caffeine influenced P wave, R or ST segment heights of ECG trace

McNamara, Ruth; Maginn, Mark; Harkin, Andrew; European Journal of Pharmacology; vol. 555; nb. 2-3; (2007); p. 194 - 198, View in Reaxys 149 of 373 Effect (Pharmacological Data)

cytotoxicity

Species or Test-System (Pharmacological Data)

Wistar rat embryo cerebral cortex cells

Concentration (Pharmacological Data)

100 - 800 μmol/l

Method (Pharmacological Data)

cells treated with title comp. for 24 or 48 h at 36.5 deg C, or at 40 deg C for 24 h; cell viability evaluated using MTT assay; absorbance measured at 550 nm

Further Details (Pharmacological Data)

MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide

Results

title comp. sign. decreased cell viability at 200, 400, and 800 μmol/l in dose-, time-, and temperature-dependent manner (figures)

Capela, Joao Paulo; Meisel, Andreas; Abreu, Artur Reis; Branco, Paula Serio; Ferreira, Luisa Maria; Lobo, Ana Maria; Remiao, Fernando; Bastos, Maria Lurdes; Carvalho, Felix; Journal of Pharmacology and Experimental Therapeutics; vol. 316; nb. 1; (2006); p. 53 - 61, View in Reaxys 150 of 373 Effect (Pharmacological Data)

monoamine transporter; interaction with

Species or Test-System (Pharmacological Data)

rat caudate putamen crude vesicular fraction

Method (Pharmacological Data)

vesicular fraction incubated with title comp. and 2 nmol/l <3H>DHTBZ for 4 h at 25 deg C; rapid filtration; liquid scintillation counting

Further Details (Pharmacological Data)

DHTBZ: dihydrotetrabenazine; VMAT2: vesicular monoamine transporter type 2; IC50 for title comp. inhibition of <3H>DHTBZ binding

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

> 100 μmol/l

Partilla, John S.; Dempsey, Allison G.; Nagpal, Ameet S.; Blough, Bruce E.; Baumann, Michael H.; Rothman, Richard B.; Journal of Pharmacology and Experimental Therapeutics; vol. 319; nb. 1; (2006); p. 237 - 246, View in Reaxys 151 of 373 Effect (Pharmacological Data)

monoamine transporter; interaction with

Species or Test-System (Pharmacological Data)

rat caudate putamen crude vesicular fraction

Method (Pharmacological Data)

vesicular fraction incubated with title comp. and 60 nmol/l <3H>dopamine for 5 min at 25 deg C; rapid filtration; liquid scintillation counting

Further Details (Pharmacological Data)

DHTBZ: dihydrotetrabenazine; VMAT2: vesicular monoamine transporter type 2; IC50 for title comp. inhibition of <3H>dopamine uptake

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

19.5 μmol/l

transmitter releasing rat caudate putamen crude vesicular fraction

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Method (Pharmacological Data)

vesicular fraction preloaded with 60 nmol/l <3H>tyramine for 20 min at 25 deg C, incubated with title comp. for 2 min at 25 deg C; rapid filtration; liquid scintillation counting; <3H>tyramine release evaluated

Further Details (Pharmacological Data)

EC50 and EMAX for title comp. inhibition of <3H>tyramine release

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

43.1 μmol/l

Results

EMAX = 98.9 percent

transmitter releasing

Species or Test-System (Pharmacological Data)

rat caudate putamen crude vesicular fraction

Method (Pharmacological Data)

vesicular fraction preloaded with 60 nmol/l <3H>dopamine for 20 min at 25 deg C, incubated with title comp. for 10 min at 25 deg C; rapid filtration; liquid scintillation counting; <3H>dopamine release evaluated

Further Details (Pharmacological Data)

EC50 and EMAX for title comp. inhibition of <3H>dopamine release

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

27 μmol/l

Results

EMAX = 65.3 percent

chronotropic

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in distilled water

Method (Pharmacological Data)

radiometric device enabling measurement of heart rate implanted; animals allowed to recover for 7 days; title comp. administered; heart rate observed for 350 min

Further Details (Pharmacological Data)

control: vehicle

Comment (Pharmacological Data)

No effect

Bexis, Sotiria; Docherty, James R.; British Journal of Pharmacology; vol. 147; nb. 8; (2006); p. 926 - 934, View in Reaxys 155 of 373 Effect (Pharmacological Data)

muscle relaxant

Species or Test-System (Pharmacological Data)

Wistar rat vas deferens epididymal portion

Sex

male

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Concentration (Pharmacological Data)

Ca. 1E-07 - 3E-05 mol/l

Kind of Dosing (Pharmacological Data)

dissolved in distilled water; added cumulatively in 0.5 log unit increments at 5 min intervals

Method (Pharmacological Data)

preparation attached to myograph transducers under 1 g tension in bath at 37 deg C in Krebs-Henseleit solution with nifedipine; placed between electrodes and stimulated; bathing fluid changed; title comp administered; isometric twitch measured

Further Details (Pharmacological Data)

stimulated every 5 min with single stimulus (0.5 ms pulses, supramaximal pulses); pD2 = logEC50, for EC50 in mol/l

Type (Pharmacological Data)

pD2

Value of Type (Pharmacological Data)

5.88 dimensionless

Results

title comp. reduced size of twitch in concentration-dependent manner (figure)

Bexis, Sotiria; Docherty, James R.; British Journal of Pharmacology; vol. 147; nb. 8; (2006); p. 926 - 934, View in Reaxys 156 of 373 Effect (Pharmacological Data)

muscle contractive

Species or Test-System (Pharmacological Data)

Wistar rat thoracic aortic ring

Sex

male

Concentration (Pharmacological Data)

1E-06 - 0.0001 mol/l

Kind of Dosing (Pharmacological Data)

dissolved in distilled water

Method (Pharmacological Data)

aortic rings attached to myograph transducers under 1 g tension in organ bath at 37 deg C in Krebs-Henseleit solution; after 30 min, tissues contracted with KCl; bathing fluid changed; title comp administered; isometric contractions measured

Further Details (Pharmacological Data)

after last dose of title comp., tissues exposed to phenylephrine to assess maximum response of vessels

Results

title comp. produced concentration-dependent increase in contraction which reached 26.5 percent of phenylephrine contraction (figure)

Bexis, Sotiria; Docherty, James R.; British Journal of Pharmacology; vol. 147; nb. 8; (2006); p. 926 - 934, View in Reaxys 157 of 373 Effect (Pharmacological Data)

muscle contractive

Species or Test-System (Pharmacological Data)

Wistar rat vas deferens

Sex

male

Concentration (Pharmacological Data)

1E-07 - 0.0001 mol/l

Kind of Dosing (Pharmacological Data)

dissolved in distilled water

Method (Pharmacological Data)

preparation attached to myograph transducers under 1 g tension in organ bath at 37 deg C in Krebs-Henseleit solution; after 30 min, tissues contracted with noradrenaline; bathing fluid changed; title comp administered; isometric contractions measured

Results

title comp. produced concentration-dependent increase in contraction (figure)

Bexis, Sotiria; Docherty, James R.; British Journal of Pharmacology; vol. 147; nb. 8; (2006); p. 926 - 934, View in Reaxys 158 of 373 Effect (Pharmacological Data) Species or Test-System (Pharmacological Data)

hypothermic Wistar rat

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Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in distilled water

Method (Pharmacological Data)

radiometric device enabling measurement of core body temperature implanted; animals allowed to recover for 7 days; title comp. administered; core body temperature observed for 350 min

Further Details (Pharmacological Data)

control: vehicle; further investigations with α2A-adrenoceptor antagonist 2-((4,5-dihydro-1H-imidazol-2-yl)methyl)-2,3-dihydro-1-methyl-1H-isoindole (BRL 44408)

Results

title comp. caused hypothermia, which reached minimum (ca. 36.3 deg C) at 60 min and gradually returned to baseline levels (ca. 38 deg C) by 300 min; effect was more pronounced and more prolongated in presence of BRL 44408

Bexis, Sotiria; Docherty, James R.; British Journal of Pharmacology; vol. 147; nb. 8; (2006); p. 926 - 934, View in Reaxys 159 of 373 Effect (Pharmacological Data)

hypertensive

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

5 - 20 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in distilled water

Method (Pharmacological Data)

radiometric device enabling measurement of blood pressure implanted; animals allowed to recover for 7 days; title comp. administered; systolic, diastolic and mean blood pressure observed for 350 min

Further Details (Pharmacological Data)

control: vehicle); further investigations with α2A-adrenoceptor antagonist 2-((4,5-dihydro-1H-imidazol-2-yl)methyl)-2,3-dihydro-1-methyl-1H-isoindole (BRL 44408)

Results

20, but not 5 mg/kg title comp. caused increase in mean blood pressure (figure), both systolic and diastolic pressures; effect was significant in time frame 121 - 300 min at dose of 20 mg/kg

Bexis, Sotiria; Docherty, James R.; British Journal of Pharmacology; vol. 147; nb. 8; (2006); p. 926 - 934, View in Reaxys 160 of 373 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in distilled water

Method (Pharmacological Data)

radiometric device enabling measurement of locomotor activity implanted; animals allowed to recover for 7 days; title comp. administered; locomotor activity observed for 350 min

Further Details (Pharmacological Data)

control: vehicle; further investigations with α2A-adrenoceptor antagonist 2-((4,5-dihydro-1H-imidazol-2-yl)methyl)-2,3-dihydro-1-methyl-1H-isoindole (BRL 44408)

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Results

only in presence of BRL 44408, title comp. significantly increased locomotor activity (table)

Bexis, Sotiria; Docherty, James R.; British Journal of Pharmacology; vol. 147; nb. 8; (2006); p. 926 - 934, View in Reaxys 161 of 373 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Swiss Webster mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 - 50 mg/kg

Method (Pharmacological Data)

mice treated with title comp.; horizontal locomotor activity measured during 90 min

Further Details (Pharmacological Data)

further investigation with 1-<2-(3,4-dichlorophenyl)ethyl>-4-methylpiperazine; control: saline

Type (Pharmacological Data)

ED50

Value of Type (Pharmacological Data)

8 mg/kg

Results

title comp. significantly dose-dependently stimulated locomotor activity, σ1 receptors involved (figures)

Brammer, Matthew K.; Gilmore, Deborah L.; Matsumoto, Rae R.; European Journal of Pharmacology; vol. 553; nb. 1-3; (2006); p. 141 - 145, View in Reaxys 162 of 373 Effect (Pharmacological Data)

receptor; binding activity

Species or Test-System (Pharmacological Data)

Sprague Dawley rat brain membranes

Sex

male

Method (Pharmacological Data)

σ1 receptor radioligand binding assay; brain membranes incubated for 120 min at 25 deg C with 5 nmol/l <3H>(+)-pentazocine and title comp.; filtered; liquid scintillation counting

Further Details (Pharmacological Data)

non-specific binding determined with haloperidol; reference comp.: 1-<2-(3,4-dichlorophenyl)ethyl>-4-methylpiperazine Ki = 6 nmol/l

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

3057 nmol/l

Brammer, Matthew K.; Gilmore, Deborah L.; Matsumoto, Rae R.; European Journal of Pharmacology; vol. 553; nb. 1-3; (2006); p. 141 - 145, View in Reaxys 163 of 373 Effect (Pharmacological Data)

receptor; binding activity

Species or Test-System (Pharmacological Data)

Sprague Dawley rat brain membranes

Sex

male

Concentration (Pharmacological Data)

3 μmol/l

Method (Pharmacological Data)

σ1 receptor radioligand binding assay; brain membranes incubated for 120 min at 25 deg C with (0.125 - 100 nmol/l) <3H>(+)-pentazocine and title comp.; filtered; liquid scintillation counting

Further Details (Pharmacological Data)

non-specific binding determined with haloperidol; reference comp.: 1-<2-(3,4-dichlorophenyl)ethyl>-4-methylpiperazine (6 nmol/l) Kd = 30 nmol/l, Bmax = 362 fmol/mg protein

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Results

title comp. significantly increased Kd from 14 to 54 nmol/l and had no effect on Bmax = 497 fmol/mg protein (table, figure)

Brammer, Matthew K.; Gilmore, Deborah L.; Matsumoto, Rae R.; European Journal of Pharmacology; vol. 553; nb. 1-3; (2006); p. 141 - 145, View in Reaxys 164 of 373 Effect (Pharmacological Data)

receptor; binding activity

Species or Test-System (Pharmacological Data)

Sprague Dawley rat brain membranes

Sex

male

Method (Pharmacological Data)

σ2 receptor radioligand binding assay; brain membranes incubated for 120 min at 25 deg C with 3 nmol/l <3H>DTG and title comp.; filtered; liquid scintillation counting

Further Details (Pharmacological Data)

non-specific binding determined with haloperidol; reference comp.: 1-<2-(3,4-dichlorophenyl)ethyl>-4-methylpiperazine Ki = 440 nmol/l

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

8889 nmol/l

Brammer, Matthew K.; Gilmore, Deborah L.; Matsumoto, Rae R.; European Journal of Pharmacology; vol. 553; nb. 1-3; (2006); p. 141 - 145, View in Reaxys 165 of 373 Effect (Pharmacological Data)

receptor; binding activity

Species or Test-System (Pharmacological Data)

Sprague Dawley rat brainstem membranes

Sex

male

Method (Pharmacological Data)

serotonin transporter radioligand binding assay; brainstem membranes incubated for 90 min at 25 deg C with 0.2 nmol/l <3H>paroxetine and title comp.; filtered; liquid scintillation counting

Further Details (Pharmacological Data)

non-specific binding determined with imipramine; reference comp.: 1-<2-(3,4-dichlorophenyl)ethyl>-4-methylpiperazine Ki > 100000 nmol/l

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

4095 nmol/l

Brammer, Matthew K.; Gilmore, Deborah L.; Matsumoto, Rae R.; European Journal of Pharmacology; vol. 553; nb. 1-3; (2006); p. 141 - 145, View in Reaxys 166 of 373 Effect (Pharmacological Data)

receptor; binding activity

Species or Test-System (Pharmacological Data)

Sprague Dawley rat striatal membranes

Sex

male

Method (Pharmacological Data)

dopamine transporter radioligand binding assay; striatal membranes incubated for 120 min at 4 deg C with 0.5 nmol/l <3H>(-)-3β-(4-fluorophenyl)tropane-2β-carboxylic acid methyl ester and title comp.; filtered; liquid scintillation counting

Further Details (Pharmacological Data)

non-specific binding determined with cocaine; reference comp.: 1-<2-(3,4-dichlorophenyl)ethyl>-4-methylpiperazine Ki = 16820 nmol/l

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

10320 nmol/l

Brammer, Matthew K.; Gilmore, Deborah L.; Matsumoto, Rae R.; European Journal of Pharmacology; vol. 553; nb. 1-3; (2006); p. 141 - 145, View in Reaxys 167 of 373 Effect (Pharmacological Data)

receptor; binding activity

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Species or Test-System (Pharmacological Data)

Sprague Dawley rat cerebral cortical membranes

Sex

male

Method (Pharmacological Data)

norepinephrine transporter radioligand binding assay; cerebral cortical membranes incubated for 120 min at 4 deg C with 0.5 nmol/l <3H>nisoxetine and title comp.; filtered; liquid scintillation counting

Further Details (Pharmacological Data)

non-specific binding determined with desipramine; reference comp.: 1-<2-(3,4-dichlorophenyl)ethyl>-4-methylpiperazine Ki = > 100000 nmol/l

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

667 nmol/l

Brammer, Matthew K.; Gilmore, Deborah L.; Matsumoto, Rae R.; European Journal of Pharmacology; vol. 553; nb. 1-3; (2006); p. 141 - 145, View in Reaxys 168 of 373 Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intravenous

Concentration (Pharmacological Data)

0.3 - 1 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in saline and administered as bolus injection

Method (Pharmacological Data)

rats administered with title comp.; blood collected every 15 min pre-dosing and at 15-min intervals for 90 min post-dosing; dialyzed; dialysates assayed for 5-hydroxytryptamine and 5-hydroxyindoleacetic acid using HPLC with electrochemical detection

Further Details (Pharmacological Data)

control: saline; ref.: fluoxetine

Results

title comp. elevated 5-hydroxytryptamine to 12- and 21-fold after 0.3 and 1.0 mg/kg, resp.; title comp. treatment did not affect plasma 5-hydroxyindoleacetic acid levels; diagram

Zolkowska, Dorota; Rothman, Richard B.; Baumann, Michael H.; Journal of Pharmacology and Experimental Therapeutics; vol. 318; nb. 2; (2006); p. 604 - 610, View in Reaxys 169 of 373 Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat blood

Sex

male

Concentration (Pharmacological Data)

0.3 - 33 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. dissolved in saline

Method (Pharmacological Data)

title comp. added to blood samples; microdialysis probes placed into blood samples; dialysate efflux collected for 15 min; assayed for 5-hydroxytryptamine levels

Further Details (Pharmacological Data)

control: saline; ref.: fluoxetine; further study: influence of fluoxetine on title comp. effect

Results

title comp. signif. increased plasma 5-hydroxytryptamine, producing 8- and 42-fold elevations at 3 and 33 μmol/l, resp.; low-dose fluoxetine (0.3 μmol/l) did not block title comp. effect; high-dose (3 μmol/l) blocked title comp. effect; diagram

Zolkowska, Dorota; Rothman, Richard B.; Baumann, Michael H.; Journal of Pharmacology and Experimental Therapeutics; vol. 318; nb. 2; (2006); p. 604 - 610, View in Reaxys 170 of 373 Effect (Pharmacological Data)

food consumption; effect on

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Species or Test-System (Pharmacological Data)

mouse

Route of Application

intraperitoneal

Method (Pharmacological Data)

II.3. Absence or Inactivation of the 5-HT4 Receptor Counteracts Inhibition of the Motivation to Consume Food Induced by Administration of MDMA or of Ecstasy. The global statistical analysis of ingestion of food reveals significant effects of genotype (F1,105=4.86; p1,105=7.24; p3,315=390.12; p3,105=2,76; p9,315=29.30; p1.59=11.93; p1.59=15.78; p3,177=3.97; p3,177=53.12; p4 receptor, compared to the mutant rodents treated with NaCl, MDMA also induces a significant diminution of ingestion of food 30 min (-69.07percent, FIG. 6A) and 1 h (-68.49percent, FIG. 6B) after its administration. This effect is no longer observed 3 h after the treatment of the mice (FIG. 6C). Furthermore, consumption of food in mice lacking the 5-HT4 receptor is significantly more elevated 1 h (+645, 56percent; p4 receptor received an injection of NaCl 9percent, 1 mg/kg of RS 39604, antagonist of the 5-HT4 receptor. In parallel thereto, a group of mice did not receive any treatment and were weighed like the previous mice and immobilized, if necessary, 10 minutes after the start of their manipulation. Ingestion of food was then measured 2 h 30 min, 3 and 5 h and each day during the recovery period. After an isolation of 3 h (procedure 1). The animals are isolated in a cage in the presence of food and water ad libitum. The weight of the food and of the animal was evaluated before and 3 h after isolation. The difference between two successive weights revealed the quantity of food ingested by the mouse. As the bottom of the cage was a grill, it was possible to evaluate the quantity of food wasted by each animal. After the superelevated cross labyrinth (procedure 2: moderate stress). The same animals were regrouped four to a cage for one week in a residence chamber. On the test day, after a period of 30 min the animals were placed in the superelevated cross labyrinth and then isolated to evaluate their consumption of food 3 h after the beginning of the test. After the superelevated cross labyrinth anticipated by an incision (procedure 3: high stress). During a period of habituation each mouse was isolated for four days (96 hours) in the presence of food and water supplied ad libitum. The weight of the mice and of the food consumed was measured daily at the same hour to establish a baseline. On the fourth day a small incision on the tail was made. A blood sample was then taken for 10 min to analyze the plasmatic rates of corticosterone before the injection and the conflict test.

Results

title compound induced significant diminution of food ingestion 30 min and 1 h after administration in wild mice and elevated food consumption 1 h and 3 h after administration in mice lacking 5-HT4 receptor

Location

Page/Page column 8-10

Patent; Centre National de la Recherche Scientifique - CNRS, an organization of France; US2006/116341; (2006); (A1) English, View in Reaxys 171 of 373 Effect (Pharmacological Data)

food consumption; effect on

Species or Test-System (Pharmacological Data)

mouse

Route of Application

intraperitoneal

Method (Pharmacological Data)

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cross labyrinth and then isolated to evaluate their consumption of food 3 h after the beginning of the test. After the superelevated cross labyrinth anticipated by an incision (procedure 3: high stress). During a period of habituation each mouse was isolated for four days (96 hours) in the presence of food and water supplied ad libitum. The weight of the mice and of the food consumed was measured daily at the same hour to establish a baseline. On the fourth day a small incision on the tail was made. A blood sample was then taken for 10 min to analyze the plasmatic rates of corticosterone before the injection and the conflict test. Results

title compound combined with RS39604 (selective 5-HT4 receptor antagonist) induced significant diminution of food ingestion 30 min and 1 h after administration in wild type and lacking 5-HT4 receptor mice; ingestion of food by wild mice was significantly more elevated 1 h and 3 h after administration of title compound/RS 39604 than that of wild animals that received only title compound, this effect was not revealed in mutant mice for the 5HT4 receptor

Location

Page/Page column 8-11

Patent; Centre National de la Recherche Scientifique - CNRS, an organization of France; US2006/116341; (2006); (A1) English, View in Reaxys 172 of 373 Effect (Pharmacological Data)

leptine rate; effect on

Species or Test-System (Pharmacological Data)

mouse

Route of Application

intraperitoneal

Method (Pharmacological Data)

III.3. Lowerings of the Rates of Leptine Detected in the Mutant Mice Lowerings of the rate of leptine detected in the mice disabled for the 5-HT4 receptor (FIG. 9, experimental MDMA paradigms) allows the proposal that the ligands of the 5-HT4 receptors can regulate the variations in the consumption of food and in weight by the control of the rates of leptine. The statistical analysis of the variations of the rates of leptine did not reveal a significant effect of the treatment with MDMA (p=0, 95). These results indicate that a single administration of MDMA does not modify the rates of leptine in the wild or in the mutant mice (FIG. 9). In the absence of the gene coding for the 5-HT4 receptor the statistical analysis of the variations of the leptine rates reveals a significant genotype effect (F1.27=10.42; p4 receptor in comparison to the wild animals (-21percent) as the use of test F of Scheff{acute over (e )} also indicates (p4 receptor received an injection of NaCl 9percent, 1 mg/kg of RS 39604, antagonist of the 5-HT4 receptor. In parallel thereto, a group of mice did not receive any treatment and were weighed like the previous mice and immobilized, if necessary, 10 minutes after the start of their manipulation. Ingestion of food was then measured 2 h 30 min, 3 and 5 h and each day during the recovery period. After an isolation of 3 h (procedure 1). The animals are isolated in a cage in the presence of food and water ad libitum. The weight of the food and of the animal was evaluated before and 3 h after isolation. The difference between two successive weights revealed the quantity of food ingested by the mouse. As the bottom of the cage was a grill, it was possible to evaluate the quantity of food wasted by each animal. After the superelevated cross labyrinth (procedure 2: moderate stress). The same animals were regrouped four to a cage for one week in a residence chamber. On the test day, after a period of 30 min the animals were placed in the superelevated cross labyrinth and then isolated to evaluate their consumption of food 3 h after the beginning of the test. After the superelevated cross labyrinth anticipated by an incision (procedure 3: high stress). During a period of habituation each mouse was isolated for four days (96 hours) in the presence of food and water supplied ad libitum. The weight of the mice and of the food consumed was measured daily at the same hour to establish a baseline. On the fourth day a small incision on the tail was made. A blood sample was then taken for 10 min to analyze the plasmatic rates of corticosterone before the injection and the conflict test.

Results

title compound administration did not modify leptine rates in wild or in mutant lacking 5HT4 receptor mice; lowerings of leptine rate was detected in mice disabled for 5-HT4 receptor

Location

Page/Page column 8-12

Patent; Centre National de la Recherche Scientifique - CNRS, an organization of France; US2006/116341; (2006); (A1) English, View in Reaxys 173 of 373 Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

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Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.89 percent NaCl and administered in a volume of 1 ml/kg

Method (Pharmacological Data)

rats treated with title comp. with LPS; after 30 - 240 min trunk blood collected and centrifuged; IL-10 determined in serum by ELISA

Further Details (Pharmacological Data)

LPS: bacterial lipopolysaccharide; IL: interleukin

Results

title comp. significantly increased LPS-induced IL-10 production after 30 - 120 min

Connor, Thomas J.; Harkin, Andrew; Kelly, John P.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 1; (2005); p. 134 - 143, View in Reaxys 174 of 373 Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.89 percent NaCl and administered in a volume of 1 ml/kg

Method (Pharmacological Data)

rats treated with title comp.; after 1 h trunk blood collected and centrifuged; IL-10 determined in serum by ELISA

Further Details (Pharmacological Data)

IL: interleukin

Comment (Pharmacological Data)

No effect

Connor, Thomas J.; Harkin, Andrew; Kelly, John P.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 1; (2005); p. 134 - 143, View in Reaxys 175 of 373 Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

1.25 - 10 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.89 percent NaCl and administered in a volume of 1 ml/kg

Method (Pharmacological Data)

rats treated with title comp. with LPS; after 60 min trunk blood collected and centrifuged; IL-10 determined in serum by ELISA

Further Details (Pharmacological Data)

LPS: bacterial lipopolysaccharide; IL: interleukin

Results

title comp. produced significant dose-dependent increase in LPS-induced IL-10 production with maximal effect at 2.5 mg/kg title comp.

Connor, Thomas J.; Harkin, Andrew; Kelly, John P.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 1; (2005); p. 134 - 143, View in Reaxys 176 of 373 Effect (Pharmacological Data)

transmitter releasing

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Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

2 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.89 percent NaCl and administered in a volume of 1 ml/kg

Method (Pharmacological Data)

rats received eight injections of 0.89 percent saline and final injection of title comp. with LPS; after 60 min trunk blood collected and centrifuged; IL-10 and TNF-α determined in serum by ELISA

Further Details (Pharmacological Data)

rats received three injections per day with interval of 3 h for 3 consecutive days; control rats received nine injections of 0.89 percent saline, LPS coadministered with last dose; LPS: bacterial lipopolysaccharide; IL: interleukin; TNF: tumor necrosis factor

Results

title comp. significantly increased IL-10 production and decreased TNF-α production

Connor, Thomas J.; Harkin, Andrew; Kelly, John P.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 1; (2005); p. 134 - 143, View in Reaxys 177 of 373 Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

2 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.89 percent NaCl and administered in a volume of 1 ml/kg

Method (Pharmacological Data)

rats received nine repeated injections of title comp.; LPS coadministered with final dose of title comp.; 60 min after last injection trunk blood collected and centrifuged; IL-10 and TNF-α determined in serum by ELISA

Further Details (Pharmacological Data)

Results

title comp. significantly increased IL-10 production and decreased TNF-α production

Connor, Thomas J.; Harkin, Andrew; Kelly, John P.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 1; (2005); p. 134 - 143, View in Reaxys 178 of 373 Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.89 percent NaCl and administered in a volume of 1 ml/kg

Method (Pharmacological Data)

rats pretreated with normal sheep serum (NSS) or anti-IL-10 antisera (anti-IL10) and immediatedly treated with title comp. with LPS; after 60 min blood obtained by cardiac puncture; IL-10 and TNF-α determined in serum by ELISA

Further Details (Pharmacological Data)

LPS: bacterial lipopolysaccharide; IL: interleukin; TNF: tumor necrosis factor

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Results

title comp. increased IL-10 production in NSS-treated but not in anti-IL10-treated rats; title comp. significantly decreased TNF-α production in both NSS- and anti-IL10-treated rats

Connor, Thomas J.; Harkin, Andrew; Kelly, John P.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 1; (2005); p. 134 - 143, View in Reaxys 179 of 373 Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

2 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.89 percent NaCl and administered in a volume of 1 ml/kg

Method (Pharmacological Data)

sham-operated or adrenalectomized rats treated with title comp. with LPS; after 60 min blood obtained and centrifuged; IL-10 and TNF-α determined in serum by ELISA

Further Details (Pharmacological Data)

LPS: bacterial lipopolysaccharide; IL: interleukin; TNF: tumor necrosis factor

Results

title comp. significantly increased IL-10 production and significantly decreased TNF-α production in both sham-operated and adrenalectomized rats

Connor, Thomas J.; Harkin, Andrew; Kelly, John P.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 1; (2005); p. 134 - 143, View in Reaxys 180 of 373 Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

2 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.89 percent NaCl and administered in a volume of 1 ml/kg

Method (Pharmacological Data)

chemically sympathectomized rats treated with title comp. with LPS; after 60 min blood obtained and centrifuged; IL-10 and TNF-α determined in serum by ELISA

Further Details (Pharmacological Data)

chemical sympathectomy produced by treatment with 6-hydroxydopamine; LPS: bacterial lipopolysaccharide; IL: interleukin; TNF: tumor necrosis factor

Results

title comp. significantly increased IL-10 production and non-significantly decreased TNF-α production

Connor, Thomas J.; Harkin, Andrew; Kelly, John P.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 1; (2005); p. 134 - 143, View in Reaxys 181 of 373 Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

2 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.89 percent NaCl and administered in a volume of 1 ml/kg

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Method (Pharmacological Data)

rats treated with title comp. with LPS; 60 min later blood obtained and centrifuged; IL-10 and TNF-α determined in serum by ELISA

Further Details (Pharmacological Data)

further investigations with chlorisondamine and nadolol; LPS: bacterial lipopolysaccharide; IL: interleukin; TNF: tumor necrosis factor

Results

title comp. significantly increased IL-10 production and significantly decreased TNF-α production; effect of title comp. on IL-10 production was inhibited by peripheral β-adrenoceptor blockade but not by ganglionic blockade

Connor, Thomas J.; Harkin, Andrew; Kelly, John P.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 1; (2005); p. 134 - 143, View in Reaxys 182 of 373 Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

2 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.89 percent NaCl and administered in a volume of 1 ml/kg

Method (Pharmacological Data)

normal or chemically sympathectomized (CSE) rats treated with title comp. with LPS; after 60 min spleen tissue obtained and homogenized; noradrenaline determined by high-performance liquid chromatography

Further Details (Pharmacological Data)

chemical sympathectomy produced by treatment with 6-hydroxydopamine; LPS: bacterial lipopolysaccharide

Comment (Pharmacological Data)

No effect

Connor, Thomas J.; Harkin, Andrew; Kelly, John P.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 1; (2005); p. 134 - 143, View in Reaxys 183 of 373 Effect (Pharmacological Data)

releasing hormones

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

2 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.89 percent NaCl and administered in a volume of 1 ml/kg

Method (Pharmacological Data)

sham-operated or adrenalectomized rats treated with title comp. with LPS; after 60 min blood obtained and centrifuged; corticosterone determined in serum by enzyme immunoassay

Further Details (Pharmacological Data)

LPS: bacterial lipopolysaccharide

Comment (Pharmacological Data)

No effect

Connor, Thomas J.; Harkin, Andrew; Kelly, John P.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 1; (2005); p. 134 - 143, View in Reaxys 184 of 373 Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat blood

Sex

male

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Concentration (Pharmacological Data)

0.1 - 10 mg/l

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.89 percent NaCl

Method (Pharmacological Data)

diluted whole blood treated with title comp.; after 1 h LPS added; cells incubated for further 24 h; 37 deg C; 5 percent CO2; IL-10 determined in supernatant by ELISA

Further Details (Pharmacological Data)

LPS: bacterial lipopolysaccharide; IL: interleukin

Comment (Pharmacological Data)

No effect

Connor, Thomas J.; Harkin, Andrew; Kelly, John P.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 1; (2005); p. 134 - 143, View in Reaxys 185 of 373 Effect (Pharmacological Data)

metabolic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Method (Pharmacological Data)

rats with cannula implanted above striatum; administration of microdialysis probe under anaesthesia; 12 - 15 h later title comp. was injected; dialysate samples collected every 20 min for 2 h; metabolites of N-Me-α-MeDA determined by HPLC-CEAS

Further Details (Pharmacological Data)

α-MeDA: α-methyldopamine; HPLC-CEAS: high performance liquid chromatography with coulometric electrode array system; further investigation with inhibitor of γ-glutamyl transpeptidase, acivicin; data were confirmed using HPLC-MS/MS

Results

title comp. induced levels of glutathione (GSH) and N-acetylcysteine (NAC) conjugates of N-Me-α-MeDA; acivicin increased concentrations of GSH and NAC conjugates of N-Me-αMeDA in brain dialysate (figure)

Jones, Douglas C.; Duvauchelle, Christine; Ikegami, Aiko; Olsen, Christopher M.; Lau, Serrine S.; De La Torre, Rafael; Monks, Terrence J.; Journal of Pharmacology and Experimental Therapeutics; vol. 313; nb. 1; (2005); p. 422 - 431, View in Reaxys 186 of 373 Effect (Pharmacological Data)

transmitter release; inhibition of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Method (Pharmacological Data)

rats were treated with title comp.; 7 d later monoamine concentrations in multiply brain regions; HPLC-CEAS

Further Details (Pharmacological Data)

HPLC-CEAS: high performance liquid chromatography with coulometric electrode array system

Results

title comp. decreased both serotonin and 5-hydroxyindoleacetic acid in striatum, cortex, hippocampus, and hypothalamus (figure)

hyperthermic Sprague-Dawley rat

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Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Method (Pharmacological Data)

rats were treated with title comp.; body temperature was measured every 30 min for 4 h; rectal probe

Further Details (Pharmacological Data)

further studies using inhibitor of γ-glutamyl transpeptidase, acivicin

Results

title comp. mediated hyperthermia, which was attenuated by acivicin (figure)

neurotoxicity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intracerebral

Concentration (Pharmacological Data)

100 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.15 mol/l NaCl; perfusion at flow rate of 1.8 μl/min for 8 h using dialysis probe implanted into striatum

Method (Pharmacological Data)

animals killed 5 d after treatment; brains removed; dopamine and serotonin content in striatal homogenate measured by HPLC with amperometric detection

Results

striatal conc. of dopamine and serotonin were not significantly altered by title comp.

Darvesh, Altaf S.; Yamamoto, Bryan K.; Gudelsky, Gary A.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 2; (2005); p. 694 - 701, View in Reaxys 189 of 373 Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.15 mol/l NaCl; injected 4 times with 2 h intervals

Method (Pharmacological Data)

animals killed 5 d after title comp. treatment; brains removed; serotonin content in striatal homogenate measured by HPLC with amperometric detection

Further Details (Pharmacological Data)

further investigation on mechanism of action using neuronal NO synthase inhibitor Smethyl-L-thiocitrulline

Results

title comp. resulted in 60 percent depletion of striatal serotonin conc.; title comp.-induced neurotoxicity involved NO-dependent mechanism

Darvesh, Altaf S.; Yamamoto, Bryan K.; Gudelsky, Gary A.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 2; (2005); p. 694 - 701, View in Reaxys 190 of 373 Effect (Pharmacological Data)

hyperthermic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

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Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.15 mol/l NaCl; injected 4 times with 2 h intervals

Method (Pharmacological Data)

rectal temperature obtained from rats maintained at 24 deg C and treated with title comp.

Further Details (Pharmacological Data)

further investigations on mechanism of action using neuronal NO synthase inhibitor Smethyl-L-thiocitrulline

Results

title comp. increased body temperature; NO-independent mechanism

Darvesh, Altaf S.; Yamamoto, Bryan K.; Gudelsky, Gary A.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 2; (2005); p. 694 - 701, View in Reaxys 191 of 373 Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.15 mol/l NaCl; injected 4 times with 2 h intervals

Method (Pharmacological Data)

dialysis samples collected via dialysis probe inserted through guide cannula into striatum at 1-h intervals for 9 h after first injection of title comp.; NO assayed by spectrophotometric quantifying nitrate/nitrite conc. using Griess reagent

Further Details (Pharmacological Data)

probe connected with pump delivered Dulbecco's phosphate-buffered saline with 1.2 mmol/l CaCl2 at rate of 1.8 μl/min

Results

title comp. significantly increased nitric oxide content to approx. 175 percent of baseline level between 3rd and 4th injections; nitric oxide content remained elevated at least 3 h after last injection; single injection had no effect

Darvesh, Altaf S.; Yamamoto, Bryan K.; Gudelsky, Gary A.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 2; (2005); p. 694 - 701, View in Reaxys 192 of 373 Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.15 mol/l NaCl; injected 4 times with 2 h intervals

Method (Pharmacological Data)

animals killed 24 h after first title comp. injection; brains removed; striatum dissected; nitrotyrosine content in hydrolyzed protein samples measured by HPLC with amperometric detection

Results

title comp. significantly increased nitrotyrosine content in striatum

Darvesh, Altaf S.; Yamamoto, Bryan K.; Gudelsky, Gary A.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 2; (2005); p. 694 - 701, View in Reaxys 193 of 373 Effect (Pharmacological Data)

enzyme; induction of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

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Route of Application

subcutaneous

Concentration (Pharmacological Data)

40 mg/kg

Method (Pharmacological Data)

jugular vein cannulated rats, 500 μl of blood collected 30 min before and 4 h after title comp. administration; serum creatine levels determined using Vitros creatine kinase slides

Further Details (Pharmacological Data)

control: saline

Results

title comp. significantly elevated serum creatine kinase levels (955 IU/l after treatment vs 373.2 IU/l in control group)

Rusyniak, Daniel E.; Tandy, Stephany L.; Hekmatyar; Mills, Edward; Smith, David J.; Bansal, Navin; MacLellan, Darcy; Harper, Mary-Ellen; Sprague, Jon E.; Journal of Pharmacology and Experimental Therapeutics; vol. 313; nb. 2; (2005); p. 629 - 639, View in Reaxys 194 of 373 Effect (Pharmacological Data)

body temperature; increase of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

40 mg/kg

Method (Pharmacological Data)

anesthetized rats treated with title comp., body temperature measured for 180 min using fiber optic temperature probes placed 1-2 cm into the rectum

Further Details (Pharmacological Data)

control: saline

Results

title comp. induced a rapid increase in core body temperature (37.7 deg C before injection vs 39.4 deg C 120 min after)

muscle temperature; increase of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

40 mg/kg

Method (Pharmacological Data)

anesthetized rats treated with title comp., sceletal muscle temperature measured for 180 min using fiber optic temperature probes placed into the lateral hind leg

Further Details (Pharmacological Data)

control: saline

Results

title comp. induced a rapid increase in sceletal muscle temperature (37.1 deg C before injection vs 38.9 deg C 150 min after)

metabolic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

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Concentration (Pharmacological Data)

40 mg/kg

Method (Pharmacological Data)

anesthetized rats treated with title comp., β-ATP levels measured for 3 h in vivo using 31P nuclear magnetic resonance method

Further Details (Pharmacological Data)

control: saline

Results

β-ATP signal area significantly decreased 150 and 180 min after title comp. administration (approximately 15 percent from baseline)

metabolic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

40 mg/kg

Method (Pharmacological Data)

anesthetized rats treated with title comp., inorganic phosphate levels measured for 3 h in vivo using 31P nuclear magnetic resonance method

Further Details (Pharmacological Data)

control: saline

Results

title comp. significantly increased inorganic phosphate levels at 150 and 180 min after admnistration of title comp. (88 percent increase)

acidic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

40 mg/kg

Method (Pharmacological Data)

31P

anesthetized rats treated with title comp., intracellular pH measured for 3 h in vivo using nuclear magnetic resonance method

Further Details (Pharmacological Data)

control: saline; pH measured based on the chemical shift of inorganic phosphate (Pi) relative to phosphocreatine

Results

title comp. significantly decreased pH at 30 and 90-180 min after administration of title comp. (figure)

metabolic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

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Concentration (Pharmacological Data)

40 mg/kg

Method (Pharmacological Data)

anesthetized rats treated with title comp., phosphocreatine levels measured for 3 h in vivo using 31P nuclear magnetic resonance method

Further Details (Pharmacological Data)

control: saline

Results

title comp. showed a trend to decrease posphocreatine levels (8 percent decrease, nonsignificant)

metabolic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

40 mg/kg

Kind of Dosing (Pharmacological Data)

in 1 ml H2O

Method (Pharmacological Data)

rats treated with title comp. and sacrificed 1 h later, mitochondria isolated from the hind legs; oxygen consumption monitored using a Clarc oxygen electrode, effect of title comp. on mitochondrial oxidative phosphorylation studied

Further Details (Pharmacological Data)

control: H20; RCI: respiratory control index; ADP: adenosine diphosphate; reaction mixture contained either glutamate and malate (complex 1) or succinate and rotenone (complex 2)

Results

title comp. slightly increased complex 1-mediated RCI but had no effect on all other paramethers including ADP to oxygen ratio

metabolic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Concentration (Pharmacological Data)

0.1 - 5 mmol/l

Method (Pharmacological Data)

mitochondria isolated from the rat hind legs; oxygen consumption monitored using a Clarc oxygen electrode, rates of respiration determined after consecutive additions of ADP, title comp. and ADP, DNP; RCI and ADP to oxygen ratio calculated

Further Details (Pharmacological Data)

control: saline; RCI: respiratory control index; DNP: 2,4-dinitrophenol; ADP: adenosine diphosphate; reaction mixture contained either glutamate and malate (complex 1) or succinate and rotenone (complex 2)

Results

lower conc. of title comp. had no effect on either of the parameters; 5.0 mmol/l significantly decreased RCI and slightly decreased the rate of DNP-uncoupled succinate-fueled respiration

enzyme; inhib. of

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Species or Test-System (Pharmacological Data)

L6 myotubes

Concentration (Pharmacological Data)

0.1 - 5 mmol/l

Method (Pharmacological Data)

L6 myotubes alone or with hepatocyte coculture were treated with title comp., incubated for 3 h at 37 deg C, 5 percent CO2, 95 percent O2, harvested and sonicated; 50 μl of this sample were mixed with 200 μl of creatine kinase assay reagent, absorbance measured

Further Details (Pharmacological Data)

control: Dulbecco's phosphate-buffered saline (DPBS); positive control: 2,4-dinitrophenol

Comment (Pharmacological Data)

No effect

behavioural symptoms

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

40 mg/kg

Method (Pharmacological Data)

rats treated with title comp.; behavior observed

Results

title comp. induced stereotypical serotonin behavioral syndrome

transport; induction of

Species or Test-System (Pharmacological Data)

HEK293 cells expressing human SERT

Concentration (Pharmacological Data)

0.1 - 30 μmol/l

Method (Pharmacological Data)

cells loaded with <3H>MPP(1+) (10 μmol/l, 0.4 Ci/mmol) for 30 min and superfused with buffer containing title comp.; 4-min fractions collected, and MPP(1+) efflux determined; EC50 for title comp. calculated

Further Details (Pharmacological Data)

further investigation by blocking SERT with clomipramine (3 μmol/l); SERT: serotonin transporter; MPP(1+): 1-methyl-4-phenylpyridinium

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

1.1 μmol/l

Results

title comp. dose-dependently stimulated SERT-mediated release

transport; induction of

Species or Test-System (Pharmacological Data)

human neuroblastoma SK-N-MC cells expressing human NET

Concentration (Pharmacological Data)

0.1 - 10 μmol/l

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Method (Pharmacological Data)

cells loaded with <3H>MPP(1+) (0.1 μmol/l, 29 Ci/mmol) for 20 min and superfused with buffer containing title comp.; 4-min fractions collected, and MPP(1+) efflux determined; EC50 for title comp. calculated

Further Details (Pharmacological Data)

further investigation by blocking NET with mazindol (10 μmol/l); NET: norepinephrine transporter; MPP(1+): 1-methyl-4-phenylpyridinium

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

0.64 μmol/l

Results

title comp. dose-dependently stimulated NET-mediated release

transport; induction of

Species or Test-System (Pharmacological Data)

human neuroblastoma SK-N-MC cells expressing human DAT

Concentration (Pharmacological Data)

0.3 - 30 μmol/l

Method (Pharmacological Data)

cells loaded with <3H>MPP(1+) (6 μmol/l, 0.2 Ci/mmol) for 20 min and superfused with buffer containing title comp.; 4-min fractions collected, and MPP(1+) efflux determined; EC50 for title comp. calculated

Further Details (Pharmacological Data)

further investigation by blocking DAT with mazindol (10 μmol/l); DAT: dopamine transporter; MPP(1+): 1-methyl-4-phenylpyridinium

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

3.2 μmol/l

Results

title comp. dose-dependently stimulated DAT-mediated release

transport; inhibition of

Species or Test-System (Pharmacological Data)

HEK-293 cells expressing human SERT

Concentration (Pharmacological Data)

Ca. 0.1 - 100 μmol/l

Method (Pharmacological Data)

cells preincubated with title comp. for 2 min, and uptake started by addition of <3H>serotonin (1 μmol/l, 0.14 Ci/mmol); after incubation for 2.5 min at 25 deg C radioactivity remaining in each well determined

Further Details (Pharmacological Data)

nonspecific uptake determined in presence of clomipramine (3 μmol/l); SERT: serotonin transporter

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

8.3 μmol/l

Results

title comp. dose-dependently inhibited serotonin uptake

transport; inhibition of human neuroblastoma SK-N-MC cells expressing human DAT

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Concentration (Pharmacological Data)

Ca. 0.2 - 200 μmol/l

Method (Pharmacological Data)

cells preincubated with title comp. for 2 min, and uptake started by addition of <3H>dopamine (1 μmol/l, 0.14 Ci/mmol); after incubation for 2.5 min at 25 deg C radioactivity remaining in each well determined

Further Details (Pharmacological Data)

nonspecific uptake determined in presence of mazindol (10 μmol/l); DAT: dopamine transporter

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

13.9 μmol/l

Results

title comp. dose-dependently inhibited dopamine uptake

transport; inhibition of

Species or Test-System (Pharmacological Data)

human neuroblastoma SK-N-MC cells expressing human NET

Concentration (Pharmacological Data)

Ca. 0.1 - 100 μmol/l

Method (Pharmacological Data)

cells preincubated with title comp. for 2 min, and uptake started by addition of <3H>norepinephrine (1 μmol/l, 0.14 Ci/mmol); after incubation for 2.5 min at 25 deg C radioactivity remaining in each well determined

Further Details (Pharmacological Data)

nonspecific uptake determined in presence of mazindol (10 μmol/l); NET: norepinephrine transporter

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

1.9 μmol/l

Results

title comp. dose-dependently inhibited norepinephrine uptake

biotransformation

Species or Test-System (Pharmacological Data)

membranes of E. coli expressing P450 CYP2D6, Phe120Ala

Concentration (Pharmacological Data)

<= 200 μmol/l

Method (Pharmacological Data)

E. coli membranes preincubated with title comp. in phosphate buffer, pH 7.4 at 37 deg C for 5 min; after addition of NADPH regenerating system, reaction allowed to proceed for 10 min; analyzed by HPLC; products identified by LC-MS

Further Details (Pharmacological Data)

NADPH regenerating system: NADPH, glucose-6-phosphate, and glucose-6-phosphate dehydrogenase

Results

Km: 11.8, 14.5, and 11.2 μmol/l for 3,4-dihydroxy-, N-dealkyl-, and N-hydroxy- oxidation products, respectively; Vmax: 2.2 min-1nmol/l-1 CYP, 3.5 min-1, and 7.1 min-1nmol/l-1 CYP for above products, respectively

Metabolite XRN (Pharmacological Data)

3251333; 150196; 10157341

Metabolite (Pharmacological Data)

(+/-)-DHMA; 3,4-methylenedioxyamphetamine; N-Hydroxy-Methylenedioxymethamphetamine

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211 of 373

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

membranes of Escherichia coli expressing P450 CYP2D6

Concentration (Pharmacological Data)

<= 200 μmol/l

Method (Pharmacological Data)

Further Details (Pharmacological Data)

NADPH regenerating system: NADPH, glucose-6-phosphate, and glucose-6-phosphate dehydrogenase

Results

Km: 1.9 μmol/l; Vmax: 1.2 min-1nmol-1 CYP

Metabolite XRN (Pharmacological Data)

3251333

Metabolite (Pharmacological Data)

(+/-)-DHMA

muscle contractive

Species or Test-System (Pharmacological Data)

human skeletal muscle strip

Concentration (Pharmacological Data)

100 - 1000 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. was prepared in double distilled water

Method (Pharmacological Data)

muscle cumulative dose-response curve for caffeine (0.5-32 mmol/l) or halothane (0.5-4 percent) in presence of title comp. (10 min prior tested drugs) recorded with mechanoelectrical transducer; threshold for contracture (force >= 2 mN) determined

Further Details (Pharmacological Data)

reference comp.: succinylcholine (500 μmol/l, showed similar to title comp. effects); MHS: malignant hyperthermia-susceptible (contracture to caffeine (C) and halothane (H)); MHN: malignant hyperthermia-negative (absence of contracture to C or H)

Results

in MHN muscles title comp. shifted dose-response curve for caffeine from 3 to 1.5 mmol/l and for halothane from 4 to 2 percent, at 100 and 1000 μmol/l, resp.; in MHS muscle 500 μmol/l of title comp. shifted caffeine contracture conc. from 1.5 to 1 mmol/l

Klingler, Werner; Heffron, James J. A.; Jurkat-Rott, Karin; O'Sullivan, Grainne; Alt, Andreas; Schlesinger, Friedrich; Bufler, Johannes; Lehmann-Horn, Frank; Journal of Pharmacology and Experimental Therapeutics; vol. 314; nb. 3; (2005); p. 1267 - 1273, View in Reaxys 213 of 373 Effect (Pharmacological Data)

muscle contractive

Species or Test-System (Pharmacological Data)

human skeletal muscle strip

Concentration (Pharmacological Data)

<= 4 mmol/l

Kind of Dosing (Pharmacological Data)

title comp. was prepared in double distilled water; title comp. added cumulatively

Method (Pharmacological Data)

muscle strips from malignant hyperthermia (MH)-susceptible (MHS), MH-negative (MHN), MH-equivocal (MHE) or RyR1M patients treated with title comp.; contraction response (increase in force >2 mN) to title comp. recorded with mechanoelectrical transducer

Further Details (Pharmacological Data)

reference comp.: succinylcholine (had no effect in MHS or in MHN); MHS: contracture to caffeine (C) and halothane (H); MHN: absence of contracture to C and H; MHE: reacted to only C or H; RyR1M: ryanodine receptor type 1 mutation (determined in MHS)

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Results

3 of 8 MHS strips reacted at >= 500 μmol/l title comp.: strips of R614C carrier contracted at 500 μmol/l; 2 strips with unknown RyR1 mutations reacted at 1 and 2 mmol/l, resp.; MHE strips reacted at 2 mmol/l; MHN strips showed no effect up to 4 mmol/l

intracellular Ca(2+); increase of

Species or Test-System (Pharmacological Data)

human skeletal muscle

Concentration (Pharmacological Data)

100 - 1000 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. was prepared in double distilled water

Method (Pharmacological Data)

myotubes incubated with 2 μmol/l fura-2 acetylmethyl ester for 30 min at 37 deg C; title comp. administered to the bath using superfusion system; changes of intracellular Ca(2+) measured by fluorescence ratio during excitation at 340 and 380 nm

Further Details (Pharmacological Data)

control: vehicle; further investigation with blocker of nicotinic acetylcholine receptors αbungarotoxin; MHN: malignant hyperthermia negative (absence of contracture in response to both caffeine and halothane)

Results

title comp. dose-dependently induced Ca(2+) transients in normal (MHN) myotubes via activation of nicotinic acetylcholine receptors (figure)

Ca(2+) release; increase of

Species or Test-System (Pharmacological Data)

rat skeletal muscle sarcoplasmic reticulum

Concentration (Pharmacological Data)

Ca. 50 - 700 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. was prepared in double distilled water

Method (Pharmacological Data)

rat muscle heavy SR incubated with Ca(2+) chelometric dye antipyralazo III; Ca(2+) flux monitored continuously with diode-array spectrophotometer in dual wavelength mode at 710 and 790 nm during title comp. application to measure Ca(2+) release

Further Details (Pharmacological Data)

control: vehicle; further investigation with ryanodine, halothane; succinylcholine as reference comp.; SR: sarcoplasmic reticulum

Comment (Pharmacological Data)

No effect

currents; induction of

Species or Test-System (Pharmacological Data)

human embryonic kidney 293 cells

Concentration (Pharmacological Data)

100 - 1000 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. was prepared in double distilled water

Method (Pharmacological Data)

patch-clamp measurements (whole-cell configuration) performed on cells, expressing nAChR; data recorded with patch-clamp amplifier; holding potential was -40 mV; piezodriven ultrafast perfusion system used for title comp. application

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Further Details (Pharmacological Data)

control: vehicle; reference comp.: acetylcholine; further investigation with pancuronium, a competitive inhibitor of nAChR channels; nAChR: nicotinic acetylcholine receptor

Results

title comp. dose-dependently activated nAChR currents; maximal current activated by title comp. was 0.17 of that induced by acetylcholine and was completely but reversibly antagonized by pancuronium (figure)

acidic

Species or Test-System (Pharmacological Data)

human skeletal muscle

Concentration (Pharmacological Data)

500 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. was prepared in double distilled water

Method (Pharmacological Data)

cells superfused in chamber (37 deg C, 50 μl/min) using computer-controlled pump; after stopping perfusion title comp. applied and metabolism of myotubes monitored using pHsensitive microphysiometer measuring cell proton secretion in chamber

Further Details (Pharmacological Data)

control: vehicle; slope of pH decrease corresponds to metabolic activation; MHN: malignant hyperthermia negative (absence of contracture in response to both caffeine and halothane); further investigation with α-bungarotoxin

Results

title comp. applied to myotubes from MHN patients resulted in phasic-tone increase in acidification rate; β-ungarotoxin drastically reduced title comp.-induced activation (figure)

muscle contractive

Species or Test-System (Pharmacological Data)

human skeletal muscle

Concentration (Pharmacological Data)

100 - 1000 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. was prepared in double distilled water

Method (Pharmacological Data)

muscle cumulative dose-response curve for caffeine (0.5-32 mmol/l) or halothane (0.5-4 percent) in presence of title comp. (10 min prior tested drugs) recorded with mechanoelectrical transducer; increase of contracture and twitch force amplitude determined

Further Details (Pharmacological Data)

control: caffeine or halothane alone; succinylcholine as reference comp.; MHS, MHN: malignant hyperthermia sensitive (contracture to caffeine and halothane) and negative (absence of contracture), resp.

Results

title comp. (100 μmol/l) caused increase of muscle contracture amplitude and twitch force amplitude for 2 mmol/l caffeine and 2 percent halothane both in MHS and MHN muscles; similar effect was shown for 500 μmol/l of succinylcholine (figure)

hypothermic

Species or Test-System (Pharmacological Data)

Dark Agouti rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 mg/kg

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Kind of Dosing (Pharmacological Data)

dissolved in 0.9 percent w/v saline

Method (Pharmacological Data)

rats housed at 15 or 30 deg C; treatment with title comp.; rectal temperature was measured for 90 min

Further Details (Pharmacological Data)

saline control; further investigations using dopamine D2 receptor subtype antagonist (remoxipride), or D1 receptor antagonist (SCH23390)

Results

title comp. at 15 deg C rapidly decreased rectal temperature; dopamine D2 but not D1 receptor antagonist blocked effect of title comp.; title comp. at 30 deg C produced modest, but sustained increase of rectal temperature (figure)

Green, A. Richard; O'Shea, Esther; Saadat, Kathryn S.; Elliott, J. Martin; Colado, M. Isabel; British Journal of Pharmacology; vol. 146; nb. 2; (2005); p. 306 - 312, View in Reaxys 220 of 373 Effect (Pharmacological Data)

hypothermic

Species or Test-System (Pharmacological Data)

Dark Agouti rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.9 percent w/v saline

Method (Pharmacological Data)

rats housed at 15 or 30 deg C; treatment with title comp.; skin temperature of tail was measured for 90 min

Further Details (Pharmacological Data)

saline control; further investigations using title comp.-lesioned rats (three doses given at 3 h intervals)

Results

title comp. decreased tail temperature at 30 deg C, but had no effect at 15 deg C; title comp. decreased tail temperature in rats lesioned with title comp. at 30 deg C (figure)

transmitter release; inhibition of

Species or Test-System (Pharmacological Data)

Dark Agouti rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.9 percent w/v saline

Method (Pharmacological Data)

rats housed at 20 deg C; three doses of title comp. were given at 3 h intervals; 7 days later concentration of 5-HT was measured in brain regions (cortex, hippocampus, striatum); high-performance liquid chromatography

Further Details (Pharmacological Data)

saline control; 5-HT: 5-hydroxytryptamine

Results

title comp. decreased cortical and hippocampal 5-HT content by ca. 30 percent, striatal by 15 percent (table)

hypothermic Dark Agouti rat

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Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.9 percent w/v saline

Method (Pharmacological Data)

rats housed at 20 deg C; three doses of title comp. were given at 3 h intervals; then temperature was elevated to 30 deg C for 240 min with further reduction to 24 deg C for 120 min; tail temperature was measured

Further Details (Pharmacological Data)

saline control

Results

title comp. did not affect tail temperature, when rats were housed at 30 deg C, but decreased tail temperature at 24 deg C (figure)

pyrogenic

Species or Test-System (Pharmacological Data)

wild-type mouse

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in distilled water

Method (Pharmacological Data)

body temperature recorded for 300 min after title comp. injection by radiotelemetric device measuring core body temperature

Further Details (Pharmacological Data)

further investigation with 2-((4,5-dihydro-1H-imidazol-2-yl)methyl)-2,3-dihydro-1-methyl-1H-isoindole (BRL 44408), α2A-adrenoreceptor antagonist; reference comp.: clonidine, 0.1 mg/kg

Results

title comp. produced hyperthermia, reaching maximum core temperature 130 min after administration; title comp. + BRL 44408 produced sign. decrease in temperature followed by nonsign. hyperthermia (figures); clonidine resulted in hypothermia by 40 min

Bexis, Sotiria; Docherty, James R.; British Journal of Pharmacology; vol. 146; nb. 1; (2005); p. 1 - 6, View in Reaxys 224 of 373 Effect (Pharmacological Data)

pyrogenic

Species or Test-System (Pharmacological Data)

α2A-adrenoreceptor knockout mouse

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in distilled water

Method (Pharmacological Data)

body temperature recorded for 300 min after title comp. injection by radiotelemetric device measuring core body temperature

Further Details (Pharmacological Data)

clonidine (0.1 mg/kg) as reference comp. had no significant effect

Results

title comp. produced biphasic response consisting of initial hypothermic response (20 min after injection) followed by hyperthermia (40 min), maximum core temperature reached 220 min after injection, after which temperature began to decline (figures)

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Bexis, Sotiria; Docherty, James R.; British Journal of Pharmacology; vol. 146; nb. 1; (2005); p. 1 - 6, View in Reaxys 225 of 373 Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

human

Sex

male

Concentration (Pharmacological Data)

100 mg

Kind of Dosing (Pharmacological Data)

two doses administered 24 h apart

Method (Pharmacological Data)

title comp. given to 10 healthy subjects with different CYP2D6 genotypes (PM and EMs); title comp. plasma conc. determined at baseline and for up to 24 h post dosing; pharmacokinetic analysis

Further Details (Pharmacological Data)

PM (*4/*4), EMs (*1/*1, *1/*4): poor and extensive metabolisers; AUC (area under curve), Cmax (peak conc.), tmax (time of Cmax), t1/2 determined for 0-24 h and 24-48 h after doses

Results

0-24/24-48 h: title comp. Cmax, tmax, t1/2 256.8/327.2 ng/ml, 2.0/25.8 h, 8.7/14.2 h in PM, 163.3/214.2 ng/ml, 1.75/25.5 h, 6.0/8.1 h in EMs (*1/*1), 214.3/269.1 ng/ml, 2.0/25.5 h, 9.1/10.1 h in EMs (*1/*4), resp.; AUCs in PM > EMs (table)

De La Torre, Rafael; Farre, Magi; Mathuna, Brian O.; Roset, Pere N.; Pizarro, Neus; Segura, Mireia; Torrens, Marta; Ortuno, Jordi; Pujadas, Mitona; Cami, Jordi; European Journal of Clinical Pharmacology; vol. 61; nb. 7; (2005); p. 551 - 554, View in Reaxys 226 of 373 Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

human

Sex

male

Concentration (Pharmacological Data)

100 mg

Kind of Dosing (Pharmacological Data)

two doses administered 24 h apart

Method (Pharmacological Data)

title comp. given to healthy subjects with different CYP2D6 genotypes (PM and EMs); title comp. metabolite HHMA plasma conc. at baseline and up to 24 h post-dosing

Further Details (Pharmacological Data)

PM (*4/*4), EMs (*1/*1, *1/*4): poor and extensive metabolisers; HHMA: 3,4-dihydroxymethamphetamine; AUC (area under curve), Cmax (peak conc.), Tmax (time to Cmax) determined for 0-24 h and 24-48 h after doses

Results

0-24/24-48 h: HHMA Cmax, tmax, t1/2: 79.8/65.2 ng/ml, 3.0/26.0 h, 15.1/19.5 h in PM, 200.4/170.3 ng/ml, 1.0/25.5 h, 9.4/10.4 h in EMs of *1/*1, 104.1/95.0 ng/ml, 1.0/24.7 h, 25.5/35.1 h in EMs of *1/*4, resp.; AUCs in PM < than in EMs (table)

Metabolite XRN (Pharmacological Data)

3251333

Metabolite (Pharmacological Data)

(+/-)-DHMA

pharmacokinetics

Species or Test-System (Pharmacological Data)

human

Sex

male

Concentration (Pharmacological Data)

100 mg

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Kind of Dosing (Pharmacological Data)

two doses administered 24 h apart

Method (Pharmacological Data)

title comp. given to healthy subjects with different CYP2D6 genotypes (PM and EMs); title comp. metabolite HMMA plasma conc. determined and for up 24 h post-dosing

Further Details (Pharmacological Data)

PM (*4/*4), EMs (*1/*1, *1/*4): poor and extensive metabolisers; HMMA: 4-hydroxy,3-methoxymethamphetamine; AUC (area under curve), Cmax (peak conc.), Tmax (time to Cmax), t1/2 determined for 0-24 and 24-48 h after doses

Results

0-24/24-48 h: HMMA Cmax, tmax, t1/2 57.6/44.5 ng/ml, 2.0/26.9 h, 14.8/15.0 h in PM, 362.1/158.6 ng/ml, 1.75/26.5 h, 8.3/20.7 h in EMs of *1/*1, 182.6/106.0 ng/ml, 1.9/26.8 h, 12.7/14.9 h in EMs of *1/*4, resp.; AUCs in PM < than in EMs (table)

Metabolite XRN (Pharmacological Data)

3261956

Metabolite (Pharmacological Data)

4-Hydroxy-3-methoxymethamphetamine

releasing hormones

Species or Test-System (Pharmacological Data)

human

Sex

male

Concentration (Pharmacological Data)

100 mg

Kind of Dosing (Pharmacological Data)

two doses administered 24 h apart

Method (Pharmacological Data)

title comp. given to healthy subjects with CYP2D6 *4/*4 genotype; blood sampled before and for up to 6 h post-dosing; prolactin blood conc. determined

Further Details (Pharmacological Data)

placebo control

Comment (Pharmacological Data)

No effect

hyperthermic

Species or Test-System (Pharmacological Data)

human

Sex

male

Concentration (Pharmacological Data)

100 mg

Kind of Dosing (Pharmacological Data)

two doses administered 24 h apart

Method (Pharmacological Data)

title comp. or placebo given to 10 healthy subjects with different CYP2D6 genotypes (PM and EMs); oral temperature recorded before and for up to 24 h post-dosing

Further Details (Pharmacological Data)

PM (*4/*4), EMs (*1/*1, *1/*4): poor, extensive metabolisers, resp.; AUC 0-6 h: area under conc.-time curve from 0 h to 6 h after drug administration

Results

title comp. caused slight increase in temperature in all subjects, but more in PM than in EMs (*1/*1) subjects with AUC0-6h = 2.867 vs. 0.404 deg C/h, resp.

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230 of 373 Effect (Pharmacological Data)

open-field test open-field test open-field test open-field test; effect on

Species or Test-System (Pharmacological Data)

rat

Method (Pharmacological Data)

MDMA (5 and 10 mg/Kg, i.p.) produced a dose-related decrease in the number of squares crossed and rears, with concomitant immobility and increased defecation; these effects are qualitatively similar to those induced by yohimbine (2 mg/Kg, i.p. in 0.9percent saline as the vehicle). DBPs (1 and 2, 1:1 mixture 10 mg/Kg, p.o. day-1, for 7 days) were administered prior to MDMA or yohimbine administration, on the 7th day, 1 hour after the last DBPs administration (p.o.). The results are incorporated in Table 5. Similar anti-anxiogenic effects were observed on pretreatment of MDMA, followed by DBPs. TABLE 5 Effects of MDMA, yohimbine, DBPs, EPA and DHA on the open-field test in rats (on anxiogenic test model). Groups Squares Faecal (mg/Kg) n crossed Immobility Rears pellets Vehicle- 12 138.6 +/- 9.8 42.4 +/- 7.5 24.2 +/- 5.4 4.4 +/- 0.9 control (0.9percent saline)MDMA(5) 8 111.2 +/- 8.0 69.3 +/- 6.1 14.3 +/- 4.2 6.7 +/- 0.5MDMA(10) 8 74.7 +/- 5.5 80.1 +/- 7.0 11.2 +/- 3.9 8.0 +/- 2.2Yohimbine(2) 8 90.8 +/- 7.4 70.2 +/- 4.9 12.8 +/- 4.4 7.5 +/- 1.2DBPs(10) 10 128.1 +/- 7.3 49.3 +/- 8.4 18.2 +/- 6.0 5.0 +/- 0.8EPA(10) 8 116.5 +/- 9.9 70.1 +/- 5.3 12.2 +/- 4.8 6.8 +/- 3.0DHA(10) 8 122.1 +/- 5.5 59.9 +/- 7.2 14.0 +/- 5.5 5.7 +/- 4.1 The above findings suggest that ingestion of DBPs, would protect the recipients from the preand post-adverse anxiogenic effects of and cravings for MDMA and yohimbine-type drugs of abuse. EPA or DHA would not be truly effective for this purpose. There is evidence that presynaptic serotonergic, but not dopaminergic, mechanisms are involved in the enactogen-like discriminative stimulus properties of MDMA. MDMA increases the number of rat brain 5-hydroxytryptamine 5-HT1A receptors and induces increased release of 5-HT from presynaptic terminals. The MDMA-withdrawal syndrome includes this increased 5-HT release activity in rats. Post-treatment of DBPs, but not EPA or DHA, completely prevented this adverse effect in MDMA-treated rats.

Results

MDMA (5 and 10 mg/Kg, i.p.) produced a dose-related decrease in the number of squares crossed and rears, with concomitant immobility and increased defecation; Table 5

Location

Page/Page column 12-13

Patent; Ghosal, Shibnath; US2005/282781; (2005); (A1) English, View in Reaxys 231 of 373 Effect (Pharmacological Data)

enzyme; inhib. of

Species or Test-System (Pharmacological Data)

human liver cytosol

Concentration (Pharmacological Data)

50 μmol/l

Kind of Dosing (Pharmacological Data)

DMSO stock; final solvent conc. 1 percent (v/v)

Method (Pharmacological Data)

aldehyde oxidase study; phthalazine (2 μmol/l) preincubated with title comp. at 37 deg C; reaction mixture containing cytosol, EDTA and potassium phosphate buffer (pH 7.4) added; 2.5 min incubation; 1-phthalazinone in filtrate analysed by HPLC-MS

Further Details (Pharmacological Data)

EDTA: ethylenediaminetetraacetic acid

Results

enzyme activity was inhibited to 44 percent

Obach, R. Scott; Huynh, Phuong; Allen, Mary C.; Beedham, Christine; Journal of Clinical Pharmacology; vol. 44; nb. 1; (2004); p. 7 - 19, View in Reaxys 232 of 373 Effect (Pharmacological Data)

oxidant

Species or Test-System (Pharmacological Data)

hepatic stellate CFSC-2G cells

Concentration (Pharmacological Data)

5 mmol/l

Kind of Dosing (Pharmacological Data)

used as hydrochloride

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Method (Pharmacological Data)

cells treated with title comp. for up to 8 h; then incubated with fluorescent probe CMH2DCFDA for 20 min at room temp.; production of reactive oxygen species (ROS) measured by fluorimetric assay

Further Details (Pharmacological Data)

CM-H2DCFDA: 5,6-chloromethyl-2',7'-dichlorohydrofluorescein diacetate; reference comp.: menadione; further investigation with pyrrolidine dithiocarbamate (PDTC), glutathione (GSH), N-acetylcysteine (NAC)

Results

both title comp. and reference comp. provoked ROS accumulation: 2-fold increase at 30 min and significant increase up to 2 h; effect was blocked by PDTC and prevented by GSH and NAC

Montiel-Duarte, Cristina; Ansorena, Eduardo; Lopez-Zabalza, Maria Jesus; Cenarruzabeitia, Edurne; Iraburu, Maria J.; Biochemical Pharmacology; vol. 67; nb. 6; (2004); p. 1025 - 1033, View in Reaxys 233 of 373 Effect (Pharmacological Data)

metabolic

Species or Test-System (Pharmacological Data)

hepatic stellate CFSC-2G cells

Concentration (Pharmacological Data)

5 mmol/l

Kind of Dosing (Pharmacological Data)

used as hydrochloride

Method (Pharmacological Data)

cells treated with title comp. for 0.5 - 24 h; deproteinized cell suspension mixed with buffer (pH 8.0) and o-phthaldialdehyde; 15 min later the level of intracellular reduced GSH determined by fluorimetric assay

Further Details (Pharmacological Data)

further investigation with glutathione (GSH), N-acetylcysteine (NAC), buthionine sulfoximine (BSO); reference comp.: menadione

Results

title comp. decreased the level of reduced GSH (40 percent reduction for 1 h, remained depletion for 24 h); effect was prevented by GSH and NAC; additive effect was observed in presence of BSO

apoptosis induction

Species or Test-System (Pharmacological Data)

hepatic stellate CFSC-2G cells

Concentration (Pharmacological Data)

5 mmol/l

Kind of Dosing (Pharmacological Data)

used as hydrochloride

Method (Pharmacological Data)

cells treated with title comp. for 24 h; DNA fragmentation determined by cell death ELISA assay; reference comp.: menadione

Further Details (Pharmacological Data)

further invest. with glutathione (GSH), N-acetylcysteine (NAC), pyrrolidine dithiocarbamate (PDTC), buthionine sulfoximine (BSO), cytochrome P450 inhibitor quinine, parthenolide, in cells infected with adenovirus Ad5dnNIK; NIK: NF-κB-inducing kinase

Results

title comp. induced apoptosis which was not caused by oxidative stress, but was partially blocked by NF-κB activation

protein expression; induction of

Species or Test-System (Pharmacological Data)

hepatic stellate CFSC-2G cells

Concentration (Pharmacological Data)

5 mmol/l

Kind of Dosing (Pharmacological Data)

used as hydrochloride

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Method (Pharmacological Data)

cells treated with title comp. for 1 - 4 h and lysed; electrophoretic mobility shift assay and Western immunoblot analysis for nuclear factor NF-κB; autoradiography and chemiluminiscent detection

Further Details (Pharmacological Data)

reference comp.: menadione (100 μmol/l); further investigation with glutathione (GSH), Nacetylcysteine (NAC) or buthionine sulfoximine (BSO)

Results

title comp. activated NF-κB in an oxidative stress-independent fashion in contrast to reference comp.

5-hydroxytryptamine uptake; inhibition of

Species or Test-System (Pharmacological Data)

SK-N-MC cells expressing human serotonin transporter

Concentration (Pharmacological Data)

Ca. 0.1 - 10000 μmol/l

Method (Pharmacological Data)

cells transiently transfected with human serotonin transporter cDNA; 48 h later <3H>5-HT uptake experiments conducted with title comp. in Krebs-Ringer buffer; uptake of <3H>5HT determined for up to 48 h by liquid scintillation spectroscopy

Further Details (Pharmacological Data)

5-HT: 5-hydroxytryptamine (serotonin); specific <3H>5-HT uptake defined as uptake inhibitable by fluoxetine; Ki determined with 20 nmol/l <3H>5-HT

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

102 μmol/l

Results

conc.-dependent inhibition of cellular <3H>5-HT uptake; after 4 h exposure to 100 μmol/l title comp. <3H>5-HT uptake inhibited by ca. 30 percent (diagram)

Jones, Douglas C.; Lau, Serrine S.; Monks, Terrence J.; Journal of Pharmacology and Experimental Therapeutics; vol. 311; nb. 1; (2004); p. 298 - 306, View in Reaxys 237 of 373 Effect (Pharmacological Data)

5-hydroxytryptamine uptake; inhibition of

Species or Test-System (Pharmacological Data)

SK-N-MC cells expressing human dopamine transporter

Method (Pharmacological Data)

cells transiently transfected with human dopamine transporter cDNA; 48 h later <3H>5-HT uptake experiments conducted with title comp. in Krebs-Ringer buffer; uptake of <3H>5HT determined for up to 48 h by liquid scintillation spectroscopy

Further Details (Pharmacological Data)

specific <3H>5-HT uptake defined as uptake inhibitable by fluoxetine

Comment (Pharmacological Data)

No effect

Jones, Douglas C.; Lau, Serrine S.; Monks, Terrence J.; Journal of Pharmacology and Experimental Therapeutics; vol. 311; nb. 1; (2004); p. 298 - 306, View in Reaxys 238 of 373 Effect (Pharmacological Data)

dopamine uptake stimulant

Species or Test-System (Pharmacological Data)

SK-N-MC cells expressing human serotonin transporter

Concentration (Pharmacological Data)

100 μmol/l

Method (Pharmacological Data)

cells transiently transfected with human serotonin transporter (hSERT) cDNA; 48 h later <3H>dopamine (DA) uptake experiments conducted with title comp. in Krebs-Ringer buffer; uptake of DA determined for up to 48 h by liquid scintillation spectroscopy

Further Details (Pharmacological Data)

further investigations on mechanism of action with fluoxetine and nomifensine

Results

title comp. stimulated uptake of DA, by ca. 3.5-fold over control levels; maximum stimulation between 4 and 8 h (graphs); effect mediated by hSERT (diagram)

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Jones, Douglas C.; Lau, Serrine S.; Monks, Terrence J.; Journal of Pharmacology and Experimental Therapeutics; vol. 311; nb. 1; (2004); p. 298 - 306, View in Reaxys 239 of 373 Effect (Pharmacological Data)

reactive oxygen species generation stimulant

Species or Test-System (Pharmacological Data)

SK-N-MC cells expressing human serotonin transporter

Concentration (Pharmacological Data)

10 - 400 μmol/l

Method (Pharmacological Data)

cells transiently transfected with human serotonin transporter (hSERT) cDNA; loaded with 2',7'-dichlorofluorescein diacetate, exposed to title comp. for up to 24 h in Krebs-Ringer buffer; ROS generation monitored using microplate fluorescence reader

Further Details (Pharmacological Data)

ROS: reactive oxygen species; further investigations on mechanism of action with fluoxetine and nomifensine

Results

title comp. induced dose-dependent, rapid ROS generation with maximum at ca. 0.5 h (ca. 30 percent increase at 100 μmol/l), rate of ROS generation declines rapidly after the initial burst; effect requires functional hSERT

Jones, Douglas C.; Lau, Serrine S.; Monks, Terrence J.; Journal of Pharmacology and Experimental Therapeutics; vol. 311; nb. 1; (2004); p. 298 - 306, View in Reaxys 240 of 373 Effect (Pharmacological Data)

reactive oxygen species generation stimulant

Species or Test-System (Pharmacological Data)

SK-N-MC cells expressing human dopamine transporter

Concentration (Pharmacological Data)

10 - 400 μmol/l

Method (Pharmacological Data)

cells transiently transfected with human dopamine transporter (hDAT) cDNA; loaded with 2',7'-dichlorofluorescein diacetate, exposed to title comp. for up to 24 h in Krebs-Ringer buffer; ROS generation monitored using microplate fluorescence reader

Further Details (Pharmacological Data)

ROS: reactive oxygen species; further investigations on mechanism of action with fluoxetine and nomifensine

Results

title comp. induced dose-dependent, rapid ROS generation with maximum at ca. 0.5 h (ca. 20 percent increase at 100 μmol/l), rate of ROS generation declines rapidly after the initial burst; effect insensitive to fluoxetine or nomifensine

Jones, Douglas C.; Lau, Serrine S.; Monks, Terrence J.; Journal of Pharmacology and Experimental Therapeutics; vol. 311; nb. 1; (2004); p. 298 - 306, View in Reaxys 241 of 373 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

CD1 mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

0.3 - 10 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.9 percent physiological saline

Method (Pharmacological Data)

mice weighing from 25 to 30 g; preteated with title comp. according to conditioned place preference paradigm in two-compartment conditioning chamber; in test phase preference score calculated

Results

title comp. produced significant conditioned place preference only at 10 mg/kg (diagram)

Robledo, Patricia; Balerio, Graciela; Berrendero, Fernando; Maldonado, Rafael; Naunyn-Schmiedeberg's Archives of Pharmacology; vol. 369; nb. 3; (2004); p. 338 - 349, View in Reaxys 242 of 373 Effect (Pharmacological Data)

behavioural symptoms

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Species or Test-System (Pharmacological Data)

CD1 mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.9 percent physiological saline; twice daily for 5 consecutive days and once on day 6

Method (Pharmacological Data)

mice weighing from 25 to 30 g; after title comp. treatment mice received metergoline, ritanserin, timolol, prazosin, SCH 23390, or raclopride; several somatic manifestations of withdrawal evaluated for 45 min

Further Details (Pharmacological Data)

examined somatic signs: paw-tremor, body tremor, piloerection, wet-dog shakes, locomotor activity and ptosis

Results

chronic title comp. administration does not induce classical manifestations of physical dependence (diagrams)

hyperthermic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

40 mg/kg

Method (Pharmacological Data)

biceps femoris and rectal temperature taken at 1 - 3 h post-treatment by thermocouple with electrode inserted into needle or with rectal probe attached to thermocouple, resp.

Further Details (Pharmacological Data)

further investigations in presence of α1-receptor antagonist prazosin, β3-receptor antagonist cyanopindolol, or combination; saline control

Results

title comp. increased rectal and skeletal muscle temperature at 1 - 3 h; rectal temp. was decreased by α1-antagonist and muscle temperature by β3-antagonist; title comp. effect was abolished by combination of α1- and β3-antagonists

Sprague, Jon E.; Banks, Matthew L.; Cook, Valerie J.; Mills, Edward M.; Journal of Pharmacology and Experimental Therapeutics; vol. 305; nb. 1; (2003); p. 159 - 166, View in Reaxys 244 of 373 Effect (Pharmacological Data)

releasing hormones

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

40 mg/kg

Method (Pharmacological Data)

1 h after title comp. administration blood from left ventricle sampled; total T4 in serum measured by enzyme linked immunosorbent assay

Further Details (Pharmacological Data)

T4: thyroxine

Results

title comp. induced significant increase in T4 levels at 1 h after treatment

hypothermic

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Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

40 mg/kg

Method (Pharmacological Data)

title comp. administered to HYPO rats 72 h after surgery; at 1 - 3 h after treatment biceps femoris and rectal temperature taken by thermocouple with electrode inserted into needle or with rectal probe attached to thermocouple, resp.

Further Details (Pharmacological Data)

sham: received sham surgeries; HYPO: hypophysectomized; controls: sham and HYPO rats received saline, sham rats received title comp.

Results

treatment of HYPO rats with title comp. resulted in significant decrease in rectal and skeletal muscle temperatures at 2 - 3 and 1 - 3 h, resp. (vs all controls)

hypothermic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

40 mg/kg

Method (Pharmacological Data)

title comp. administered to TX rats 1 week after surgery; at 1 - 3 h after treatment rectal temperature taken with rectal probe attached to thermocouple

Further Details (Pharmacological Data)

sham: received sham surgeries; TX: thyroparathyroidectomized; further investigation with replacing thyroid hormones with levothyroxine; 3 controls: sham (1) and TX (2) rats received saline, sham rats received title comp. (3)

Results

title comp. in TX rats significantly decreased rectal temperature, producing significant hypothermia; levothyroxine replacement in TX rats partially returned response to title comp. to control (1) level

transmitter release; inhibition of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

40 mg/kg

Method (Pharmacological Data)

title comp. administered to sham, TX and HYPO rats 72 h after surgery; 7 d (sham and HYPO) or 4 d (TX) later tissue of each hemisphere of striatum and hippocampus sampled; 5-HT levels measured by high-performance liquid chromatography EC

Further Details (Pharmacological Data)

sham: received sham surgeries; HYPO: hypophysectomized; TX: thyroparathyroidectomized; 5-HT: 5-hydroxytryptamine; saline control

Results

striatal and hippocampal 5-HT conc. was significantly decreased in title comp.-treated sham rats; 5-HT decrease in hippocampus was attenuated in HYPO rats and 5-HT decrease was attenuated in both tissues in TX rats (figure)

transmitter releasing

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Species or Test-System (Pharmacological Data)

rat brain synaptosomes

Method (Pharmacological Data)

rat whole brain minus cerebellum and caudate homogenized with reserpine, nomifensine and GBR12935 added; preparation centrifuged; supernatant incubated with 5 nmol/l <3H>5-HT (1 h, 25 deg C), then title comp. added (5 min); liquid scintillation counting

Further Details (Pharmacological Data)

reference comp.: 5-HT (5-hydroxytryptamine), EC50 = 44 nmol/l; GBR12935: (diphenylmethoxy)ethyl-4-(3-phenylpropyl)-piperazine

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

72 nmol/l

Setola, Vincent; Hufeisen, Sandra J.; Grande-Allen, K. Jane; Vesely, Ivan; Glennon, Richard A.; Blough, Bruce; Rothman, Richard B.; Roth, Bryan L.; Molecular Pharmacology; vol. 63; nb. 6; (2003); p. 1223 - 1229, View in Reaxys 249 of 373 Effect (Pharmacological Data)

mitogenic

Species or Test-System (Pharmacological Data)

human heart valve interstitial cells

Concentration (Pharmacological Data)

10 μmol/l

Method (Pharmacological Data)

cells incubated with title comp. (3 d) with/without SB206553, 12 h before the end of treatment pulsed with <3H>TdR; assay for <3H>TdR incorporation by liquid scintillation counting

Further Details (Pharmacological Data)

vehicle control; reference comp.: 5-hydroxytryptamine (5-HT), 5-HT2B/2C receptor antagonist 5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo<2,3-f>indole (SB206553); TdR: thymidine deoxyribose

Results

title comp., 5-HT and SB206553 induced ca. 2.5-, 2- and 0.5-fold increase of <3H>TdR incorporation over control, resp.; coincubation with SB206553 prevented this effect of title comp. and 5-HT (figure)

mitogenic

Species or Test-System (Pharmacological Data)

human heart valve interstitial cells

Concentration (Pharmacological Data)

10 μmol/l

Method (Pharmacological Data)

cells incubated with title comp. (15 min), medium collected; immunoblot analysis of Erk 1/2 phosphorylation; total Erk 1/2 measured for comparison

Further Details (Pharmacological Data)

Results

title comp. and 5-HT (but not SB206553) induced short-term mitogenic effect (figure)

transmitter releasing

Species or Test-System (Pharmacological Data)

rat caudate synaptosomes

Method (Pharmacological Data)

caudate homogenized and centrifuged; supernatant incubated with 5 nmol/l <3H>DA (30 min, 25 deg C), then title comp. added (5 min); liquid scintillation counting

Further Details (Pharmacological Data)

reference comp.: 5-HT (5-hydroxytryptamine), EC50 > 10000 nmol/l; DA: dopamine

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Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

278 nmol/l

transmitter releasing

Species or Test-System (Pharmacological Data)

rat brain synaptosomes

Method (Pharmacological Data)

rat whole brain minus cerebellum and caudate homogenized; preparation centrifuged; supernatant incubated with 7 nmol/l <3H>NE and RTI-229 (1 h, 25 deg C), then title comp. added (30 min); liquid scintillation counting

Further Details (Pharmacological Data)

reference comp.: 5-HT (5-hydroxytryptamine), EC50 > 10000 nmol/l; NE: norepinephrine

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

110 nmol/l

receptor; binding activity

Species or Test-System (Pharmacological Data)

COS-7 cells

Concentration (Pharmacological Data)

Ca. 1E-12 - 0.0001 mol/l

Method (Pharmacological Data)

cells transiently expressing h5-HT2B receptors; radioligand displacement assay

Further Details (Pharmacological Data)

Ki values calculated using Cheng-Prusoff approximation; 5-HT: 5-hydroxytryptamine

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

500 nmol/l

agonist

Species or Test-System (Pharmacological Data)

HEK293 cells

Concentration (Pharmacological Data)

Ca. 1E-12 - 0.0001 mol/l

Method (Pharmacological Data)

stimulation of phosphatidylinositol hydrolysis via h5-HT2B receptors activation determined

Further Details (Pharmacological Data)

reference comp.: 5-HT (5-hydroxytryptamine), EC50 = 1 nmol/l

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

2000 nmol/l

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receptor density; reduction of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

2 doses per day with interval 7 h were administered for 4 d

Method (Pharmacological Data)

rats housed at ambient temp. of 26 deg C; treatment with title comp.; 3 or 7 d later parietal cortex, hippocampus or striatum homogenate was incubated with 0.05 nmol/l <3H>paroxetine for 1.5 h at 25 deg C; density of serotonin uptake sites was assessed

Further Details (Pharmacological Data)

control: saline; scintillation spectroscopy; incubation buffer (in mmol/l): 50 Tris-HCl, 120 NaCl, 5 KCl, pH 7.4; non-specific binding was defined in presence of 100 μmol/l clomipramine

Results

title comp. 3 d post-treatment reduced number of serotonin uptake sites in all cerebral areas; decrease in <3H>paroxetine binding was still present 7 d post-treatment (figure)

Pubill, David; Canudas, Anna M.; Pallas, Merce; Camins, Antonio; Camarasa, Jorge; Escubedo, Elena; Naunyn-Schmiedeberg's Archives of Pharmacology; vol. 367; nb. 5; (2003); p. 490 - 499, View in Reaxys 256 of 373 Effect (Pharmacological Data)

receptor density; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

2 doses per day with interval 7 h were administered for 4 d

Method (Pharmacological Data)

rats housed at ambient temp. of 26 deg C; treatment with title comp.; 3 or 7 d later parietal cortex, hippocampus or striatum homogenate was incubated with 2 nmol/l <3H>PK 11195 for 2 h at 0-4 deg C; PBR density was assessed; scintillation spectroscopy

Further Details (Pharmacological Data)

control: saline; peripheral-type benzodiazepine receptors (PBR) were assessed as indirect marker of microglial activation; non-specific binding was defined in presence of 10 μmol/l Ro 5-4864

Comment (Pharmacological Data)

No effect

protein expression; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

2 doses per day with interval 7 h were administered for 4 d

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Method (Pharmacological Data)

rats housed at ambient temp. of 26 deg C; treatment with title comp.; 3 or 7 d later glial activation was determined in brain sections using OX-6 antibody; immunohistochemical assay

Further Details (Pharmacological Data)

control: saline; further investigations using antibody against glial-specific marker glial fibrilliary acidic protein (GAFP)

Results

title comp. did not induced OX-6 expression in cortex or striatum, but caused some immunoreactivity in hippocampus 3 d after treatment; slight increase in GAFP immunoreactivity was seen only in hippocampus (figure)

protein expression; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

2 doses per day with interval 7 h were administered for 4 d

Method (Pharmacological Data)

rats housed at ambient temp. of 26 deg C; treatment with title comp.; 3 or 7 d later astroglial activation was determined in homogenate of parietal cortex, hippocampus or striatum by induction of HSP27; Western blotting

Further Details (Pharmacological Data)

HSP27: 27-kDa heat shock protein; result was confirmed using immunohistochemical assay in brain slices

Comment (Pharmacological Data)

No effect

pyrogenic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

2 doses per day with interval 7 h were administered for 4 d

Method (Pharmacological Data)

rats housed at environmental temp. of 22 - 26 deg C; rectal temperature was measured 1 h after first daily dose of title comp.

Further Details (Pharmacological Data)

control: saline

Results

when ambient temp. was raised to 26 deg C, title comp. exerted potent hyperthermic effect (maximum after 1st dose, 40.4 deg C); when ambient temp. was 22 deg C, no significant hyperthermic response to title comp. was obtained (figure)

receptor density; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

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Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

2 doses per day with interval 7 h were administered for 4 d

Method (Pharmacological Data)

rats housed at ambient temp. of 26 deg C; 3 or 7 d after treatment with title comp. brain was removed; striatum homogenate; incubation with 2 nmol/l <3H>GBR 12935 for 45 min at 25 deg C; density of dopaminergic terminals was assessed

Further Details (Pharmacological Data)

control: saline; <3H>GBR 12935 equilibrum binding assay; scintillation spectroscopy; incubation buffer (in mmol/l): 50 Tris-HCl, 120 NaCl, 5 KCl, pH 7.4; non-specific binding was defined in presence of 30 μmol/l bupropion

Results

title comp. 3 d after treatment decreased abundance of dopaminergic uptake sites by ca. 40 percent; number of sites returned to control value after 7 d (figure)

toxicity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

2 doses per day with interval 7 h were administered for 4 d

Method (Pharmacological Data)

rats housed at environmental temp. of 26 deg C; body weight was assessed for 11 h after begining of treatment with title comp.

Further Details (Pharmacological Data)

control: saline

Results

title comp. significantly decreased body weight after 4-th day of treatment; body weight was restored by end of observations (figure)

toxicity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

2 doses per day with interval 7 h were administered for 4 d

Method (Pharmacological Data)

rats housed at environmental temp. of 26 - 28 deg C; lethality caused by treatment with title comp. was assessed

Further Details (Pharmacological Data)

control: saline

Results

title comp. induced 55.5 percent lethality at 26 deg C when body weight was > 260 g; when body weight was < 250 g survival index was 91 percent; lethality increased when ambient temp. rose > 28 deg C

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263 of 373 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intravenous

Concentration (Pharmacological Data)

1 mg/kg

Kind of Dosing (Pharmacological Data)

used as hydrochloride; solvent: saline

Method (Pharmacological Data)

runtimes measured in runway test 5 times over 90 min intervals; treated with title comp. upon reaching goal area and allowed to experience title comp. effect for 5 min without leaving it; title comp. reinforcing effect evaluated

Further Details (Pharmacological Data)

control: vehicle

Results

title comp. significantly decreased runtimes (compared to saline alone that gradually increased runtimes over 5 consecutive runs), serving as positive reinforcer

Wakonigg, Gudrun; Sturm, Katja; Saria, Alois; Zernig, Gerald; Pharmacology; vol. 69; nb. 4; (2003); p. 180 182, View in Reaxys 264 of 373 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Long-Evans rat

Sex

male

Route of Application

intravenous

Concentration (Pharmacological Data)

1 mg/kg

Kind of Dosing (Pharmacological Data)

used as hydrochloride; solvent: saline

Method (Pharmacological Data)

Further Details (Pharmacological Data)

control: vehicle

Results

title comp. significantly decreased runtimes (compared to saline alone that gradually increased run times over 5 consecutive runs), serving as positive reinforcer

Wakonigg, Gudrun; Sturm, Katja; Saria, Alois; Zernig, Gerald; Pharmacology; vol. 69; nb. 4; (2003); p. 180 182, View in Reaxys 265 of 373 Effect (Pharmacological Data)

uptake; inhibition of

Species or Test-System (Pharmacological Data)

Wistar rat left ventricular slice

Sex

male

Kind of Dosing (Pharmacological Data)

dissolved in distilled water

Method (Pharmacological Data)

slices incubated with title comp. and <3H>noradrenaline (25 nmol/l) for 15 min at 37 deg C; filtered; incubated overnight with 3 percent trichloracetic acid at 4 deg C; <3H>noradrenaline accumulation measured

Further Details (Pharmacological Data)

nonspecific uptake determined by parallel incubation at 4 deg C; reference comp.: cocaine (-log EC50 = 6.16)

Type (Pharmacological Data)

-log EC50

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Value of Type (Pharmacological Data)

6.05 dimensionless

Cleary, Linda; Docherty, James R.; European Journal of Pharmacology; vol. 476; nb. 1-2; (2003); p. 31 - 34, View in Reaxys 266 of 373 Effect (Pharmacological Data)

receptor; binding activity

Species or Test-System (Pharmacological Data)

Wistar rat cerebral cortex membranes

Sex

male

Kind of Dosing (Pharmacological Data)

dissolved in distilled water

Method (Pharmacological Data)

noradrenaline transporter binding study; membranes incubated with title comp. and <3H>nisoxetine for 4 h at 4 deg C; filtered; scintillation cocktail incubated overnight and counted

Further Details (Pharmacological Data)

nonspecific binding determined in presence of desipramine; reference comp.: cocaine (log EC50 = 5.04)

Type (Pharmacological Data)

-log EC50

Value of Type (Pharmacological Data)

4.22 dimensionless

Cleary, Linda; Docherty, James R.; European Journal of Pharmacology; vol. 476; nb. 1-2; (2003); p. 31 - 34, View in Reaxys 267 of 373 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

CD-1 mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

1 - 9 mg/kg

Kind of Dosing (Pharmacological Data)

dose per day; dissolved in 0.9 percent saline

Method (Pharmacological Data)

repeated administration of title comp. on days 1, 3, and 5; 20 min after injection mice were placed in one of conditioning environments for 20 min; place preference paradigm was assessed

Further Details (Pharmacological Data)

saline control; further investigations using pretreatment with selective MEK inhibitor, SL327

Results

title comp. at 9 mg/kg induced conditioned place preference; SL327 completely abolished effect of title comp. (figure, table)

Salzmann, Julie; Marie-Claire, Cynthia; Le Guen, Stephanie; Roques, Bernard P.; Noble, Florence; British Journal of Pharmacology; vol. 140; nb. 5; (2003); p. 831 - 838, View in Reaxys 268 of 373 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

CD-1 mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

9 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.9 percent saline

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Method (Pharmacological Data)

administration of title comp.; locomotor activity was monitored each 15 min for 120 min

Further Details (Pharmacological Data)

saline control; further investigations using pretreatment with selective MEK inhibitor, SL327

Results

title comp. increased locomotor activity; SL327 antagonized effect of title comp. (figure)

neuroregulatoric

Species or Test-System (Pharmacological Data)

CD-1 mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

9 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.9 percent saline

Method (Pharmacological Data)

administration of title comp.; 1 h later total RNA was extracted from brain structures (caudate putamen, nucleus accumbens and hippocampus); c-fos transcription was analyzed; real-time quantitative RT-PCR

Further Details (Pharmacological Data)

saline control; further investigations using pretreatment with selective MEK inhibitor, SL327; RT-PCR: reverse transcription-polymerase chain reaction

Results

title comp. increased c-fos transcription in caudate putamen (8-fold), in nucleus accumbens (3-fold) and in hippocampus (2.5-fold); SL327 decreased effect of title comp. in caudate putamen, but not in hippocampus and nucleus accumbens (figure)

neuroregulatoric

Species or Test-System (Pharmacological Data)

CD-1 mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

9 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.9 percent saline

Method (Pharmacological Data)

administration of title comp.; 1 h later total RNA was extracted from brain structures (caudate putamen, nucleus accumbens and hippocampus); erg-1 or erg-3 transcriptions were analyzed; real-time quantitative RT-PCR

Further Details (Pharmacological Data)

saline control; further investigations using pretreatment with selective MEK inhibitor, SL327; RT-PCR: reverse transcription-polymerase chain reaction

Results

title comp. significantly increased erg 1 and erg 3 transcriptions only in caudate putamen, but not in nucleus accumbens and hippocampus; SL327 completely abolished effect of title comp. (figure)

neuroregulatoric

Species or Test-System (Pharmacological Data)

CD-1 mouse

Sex

male

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Route of Application

intraperitoneal

Concentration (Pharmacological Data)

9 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.9 percent saline

Method (Pharmacological Data)

administration of title comp.; 2 h later c-fos-positive neurons were determined in striatum; immunohistochemistry

Further Details (Pharmacological Data)

saline control; further investigations using pretreatment with selective MEK inhibitor, SL327

Results

title comp. produced 3-fold induction of c-fos-positive neurons in caudate putamen; SL327 completely abolished effect of title comp. (figure)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 mg/kg

Method (Pharmacological Data)

pairs of rats treated with title comp. and placed in black Perspex box for 10 min; social interaction assessed; experiment performed at 21 deg C or 30 deg C

Further Details (Pharmacological Data)

cocaine and d-amphetamine used as reference compounds

Results

title comp. caused overall increase in social interaction; effect was sign. greater at 30 deg C than at 21 deg C

behavioural symptoms

Species or Test-System (Pharmacological Data)

Hooded Wistar rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

0.1 - 1 mg/kg

Method (Pharmacological Data)

rats trained to self-administered title comp. in daily 2-h sessions at 21 deg C or 30 deg C under FR-1; locomotion activity measured

Further Details (Pharmacological Data)

cocaine used as reference compound

Results

rats self-administered more title comp. at 30 deg C; locomotion activity during title comp. self-administration declined by more than 50 percent at 30 deg C

hyperthermia; induction of

Species or Test-System (Pharmacological Data)

Charles River mouse

Sex

male

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Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 - 20 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.9 percent NaCl, injected in volume of 0.1 ml/100 g body weight;

Method (Pharmacological Data)

adult mice (25-30 g); 3 dose groups: 5 mice/group; mice were placed inside the environmental chamber for 24 h; tested at temp. of 20 and 30 deg C; subcutaneous temp. of mice measured using implanted transponders

Further Details (Pharmacological Data)

mice were haused at 20 deg C, 50 percent rel. hum. and 12 h light/dark cycle; standard food and water ad lib.; fasted on treatm.-day; control: saline

Results

marked dose-dependent increase in mice body temp. (max. at 30 min; elevated for more than 4 h); hyperthermic response potentiated by high ambient temp.

Carvalho, Marcia; Carvalho, Felix; Remiao, Fernando; De Lourdes Pereira, Maria; Pires-Das-Neves, Ricardo; De Lourdes Bastos, Maria; Archives of Toxicology; vol. 76; nb. 3; (2002); p. 166 - 172, View in Reaxys 275 of 373 Effect (Pharmacological Data)

toxicity

Endpoint of Effect (Pharmacological Data)

mortality

Species or Test-System (Pharmacological Data)

Charles River mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 - 20 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.9 percent NaCl, injected with 0.1 ml/100 g body weight aliquote

Method (Pharmacological Data)

mice (25-30 g); 3 dose groups;(5 mice/group); mice were placed inside the environmental chamber for 24 h; tested at temp. of 20 and 30 deg C

Further Details (Pharmacological Data)

cmice haused at 20 deg C, 50 percent rel. hum and 12 h light/dark cycle; standerd food and water ad lib.; fasted on treatm.-day; control: saline

Results

lethality was only observed at dose 20 mg/kg; deaths occured within 3 h post-dosing; 10 percent lethality at 20 deg C; 40 percent lethality at 30 deg C

hepatotoxic

Species or Test-System (Pharmacological Data)

Charles River mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 - 20 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.9 percent NaCl, injected with 0.1 ml/100 g body weight aliquote

Method (Pharmacological Data)

mice (25-30 g); 3 dose groups;(5 mice/group); mice were placed inside the environmental chamber for 24 h; tested at temp. of 20 and 30 deg C; plasma and liver samples biochem. analyzed; histolog. exam. of liver section

Further Details (Pharmacological Data)

examin. of: plasma levels of transaminases and alkaline phosphatase (ALT, AST, ALP), hepatic glutathione (GSH), hapatic lipid peroxidation

Results

no signif. changes in plasma levels of ALT, AST and ALP, in lipid peroxidation; signif. increase in thiobarbituric acid reactive subst. at highest dose and temp.; normal morphology of hepatic sections; damage

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enzyme; inhib. of

Species or Test-System (Pharmacological Data)

Charles River mouse

Sex

male

Concentration (Pharmacological Data)

5 - 20 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.9 percent NaCl, injected with 0.1 ml/100 g body weight aliquote

Method (Pharmacological Data)

mice (25-30 g); 3 dose groups;(5 mice/group); mice were placed inside the environmental chamber for 24 h; tested at temp. of 20 and 30 deg C; plasma and liver samples biochem. analyzed

Further Details (Pharmacological Data)

examin. of catalase, glutathione peroxidase (GPx), glutathione reductase (GRed), glutathione-S-transferase (GST), Cu/Zn superoxide dismutase (CuZnSOD) and Mn superoxide dismutase activities; control: saline

Results

signif. depletion of GSH at both ATs, signif. decrease in catalase act. (10, 20 mg/kg, high temp.), GRed, GST, CuZnSOD and MnSod were similar among the groups at both ATs

cardiotoxic

Endpoint of Effect (Pharmacological Data)

ultrastructural changes in myocardium

Species or Test-System (Pharmacological Data)

black C57BL/6J mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

dosed three times with intervals of 2 h

Method (Pharmacological Data)

histological procedure; 8 μm sections stained by haematoxylineosin; light microscopy; transmission electron microscopy (routine procedure for myocardium); one-way analysis of variance with Sheffe post-hoc analysis

Further Details (Pharmacological Data)

dissected specific myocardium from right atrium and ventricle using microtome; extent of damage measured counting number of altered mitochondria out of total number, and expressed as percentage values

Results

title comp. produced myocardial alterations in both atrium and ventricle: 11.68 percent and 9.41 percent of altered mitochondria, resp., without noise, and 28.89 percent and 16.79 percent of altered mitochondria, resp., at loud noise (100dBA); control: 3.50 percent and 3.65 percent, resp.

Gesi, Marco; Soldani, Paola; Lenzi, Paola; Ferrucci, Michela; Giusiani, Alberto; Fornai, Francesco; Paparelli, Antonio; Pharmacology and toxicology; vol. 91; nb. 1; (2002); p. 29 - 33, View in Reaxys 279 of 373 Effect (Pharmacological Data)

drug interaction

Species or Test-System (Pharmacological Data)

human

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

100 mg

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Kind of Dosing (Pharmacological Data)

title comp. admin. in the fasting state, with 100 ml of tap water

Method (Pharmacological Data)

9 healthy volunteers in a double blind, double dummy, placebo-controlled, randomized crossover study (1 week washout); 30 min after title comp. acute alcohol intoxication induced by the p.o. ingestion of 0.8 g/kg EtOH-containing beverage

Further Details (Pharmacological Data)

psychomotor performance (PP) examined using digit-symbol substitution test, simple reaction time measurement, and exophoria/esophoria meaurement by the Maddox-wing device for 24 h after EtOH; title comp. effect on EtOH-induced impairment of PP studied

Comment (Pharmacological Data)

No effect

drug interaction

Species or Test-System (Pharmacological Data)

human

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

100 mg

Kind of Dosing (Pharmacological Data)

title comp. admin. in the fasting state, with 100 ml of tap water

Method (Pharmacological Data)

Further Details (Pharmacological Data)

subjective effects (SE) measured using short form of Addiction Research Center Inventory + 23 different visual analog scales (measure of sedation, euphoria, stimulant effects); 4 h after EtOH; title comp. effect on EtOH-induced SE studied

Results

subjective sedation induced by EtOH reversed; longer lasting euphoria and well being than title comp. or EtOH alone; dissociation between subjective and objective sedation (graph)

drug interaction

Species or Test-System (Pharmacological Data)

human

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

100 mg

Kind of Dosing (Pharmacological Data)

title comp. admin. in the fasting state, with 100 ml of tap water

Method (Pharmacological Data)

Further Details (Pharmacological Data)

blood sampled for 6 h after title comp.; title comp. in plasma measured using GC/MS; plasma EtOH determined using GC; title comp. effect on plasma EtOH studied

Results

9-15 percent decrease of plasma EtOH (table)

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282 of 373 Effect (Pharmacological Data)

receptor; binding activity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

female

Route of Application

subcutaneous

Kind of Dosing (Pharmacological Data)

title comp. administered twice daily for four consecutive days

Method (Pharmacological Data)

time-mated rats treated with title comp. on E15; offspring sacrificed on P40; cell membrane from FC incubated in assay buffer contg. 4-1,000 pmol/l <3H>-paroxetine for 2 h at 24 deg C; radioactivity detd. by liquid scintillation counter

Further Details (Pharmacological Data)

control: saline (KD: 39.1 pmol/l); FC: frontal cortex; P: postnatal day; E: embryonic day; non-specific binding defined by citalopram (4 μmol/l)

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

37.2 pmol/l

Results

title comp. treatment commencing from E15 had no effect upon <3H>-paroxetine binding; no difference in density (Bmax) of <3H>-paroxetine binding sites; table, diagram

Kelly, Paul A.T.; Ritchie, Isobel M.; Quate, Linda; McBean, Douglas E.; Olverman, Henry J.; British Journal of Pharmacology; vol. 137; nb. 7; (2002); p. 963 - 970, View in Reaxys 283 of 373 Effect (Pharmacological Data)

receptor; binding activity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

female

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. administered twice daily for four consecutive days

Method (Pharmacological Data)

time-mated rats treated with title comp. on E15; offspring weaned; dams sacrificed on P40; cell membrane from FC incubated in assay buffer contg. <3H>-paroxetine (4-1000 pmol/l) for 2 h at 24 deg C; RA detd. by liquid scintillation counter

Further Details (Pharmacological Data)

control: saline (KD: 39.1 pmol/l); FC: frontal cortex; RA: radioactivity; E: embryonic day; non-specific binding detd. by citalopram (4 μmol/l)

Results

title comp. treatment resulted in 89 percent reduction in <3H>-paroxetine binding compared to saline treated rats

receptor; binding activity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Kind of Dosing (Pharmacological Data)

title comp. administered twice daily for four consecutive days

Method (Pharmacological Data)

neonatal rats treated with title comp. on P10/P15/P20/P25/P30/P90; sacrificed on P25, P40; cell membrane from FC incubated in assay buffer contg. 4-1,000 pmol/l <3H>-paroxetine for 2 h at 24 deg C; RA detd. by liquid scintillation counter

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Further Details (Pharmacological Data)

control: saline (KD: 33.4-40.5 pmol/l); FC: frontal cortex; NP: non-specific binding; LSC: liquid scintillation counter; rats treated on postnatal day (P) 90 sacrificed after 10 days; RA: radioactivity; non-specific binding detd. by citalopram

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

35.8 - 40.8 pmol/l

Results

title comp. treatment started on P25 or later resulted in signif. decreases in <3H>-paroxetine binding (>= 46 percent); table, diagram

neurotoxicity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. administered twice daily for four consecutive days

Method (Pharmacological Data)

neonatal rats treated with title comp. on P10; tracer 40 μCi admin. (i.v.); blood sampled (14 times); <14C> conc./glucose level detd. by LSC/GOA, resp.; sacrificed (P90); lCMRglu detd. in membrane from frontal cortex by <14C>-2-deoxyglucose ART

Further Details (Pharmacological Data)

control: saline; P: postnatal day; ART: autoradiographic technique; lCMRglu: local cerebral glucose utilization; LSC: liquid scintillation counter; GOA: glucose oxidase assay

Comment (Pharmacological Data)

No effect

neurotoxicity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

female

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. administered twice daily for four consecutive days commencing on embryonic day 15-18

Method (Pharmacological Data)

neonatal male offspring from title comp. treated dams admin. with tracer 40 μCi (i.v.); 14 times blood samples collected; <14C> conc./glucose level detd. by LSC/GOA, resp.; sacrificed (P90); lCMRglu detd. in CM from brain by <14C>-2-deoxyglucose ART

Further Details (Pharmacological Data)

control: saline; P: postnatal day; ART: autoradiographic technique; lCMRglu: local cerebral glucose utilization; LSC: liquid scintillation counter; GOA: glucose oxidase assay; CM: cell membrane

Results

increased lCMRglu in locus coeruleus (+37 percent) and in areas receiving ascending noradrenergic innervation such as anterior thalamus (+44 percent), hypothalamus (+25 percent), globus pallidus (+26 percent), septal nucleus (+24 percent) noticed in title comp. treated groups; table

Kelly, Paul A.T.; Ritchie, Isobel M.; Quate, Linda; McBean, Douglas E.; Olverman, Henry J.; British Journal of Pharmacology; vol. 137; nb. 7; (2002); p. 963 - 970, View in Reaxys

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287 of 373 Effect (Pharmacological Data)

hemodynamics; effect on

Species or Test-System (Pharmacological Data)

C57BL6 mouse

Sex

male and female

Route of Application

intravenous

Concentration (Pharmacological Data)

5 - 20 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in distilled water using an ultrasonic bath and diluted in normal saline (0.9 percent NaCl, w/v)

Method (Pharmacological Data)

mice anaesthetised with pentobarbitone; title comp. injected; blood pressure observed at 20 - 30 s, 1, 2, 3, 4, 5, and 10 min post injection

Further Details (Pharmacological Data)

further investigation with selective α2A/D-adrenoceptor antagonist BRL44408

Results

title comp. induced sign. increase in heart rate; title comp. produced short-lived pressor response with a later depressor component or only short-lived pressor response at doses of 5 mg/kg or 20 mg/kg, resp., by action via α2A/D-adrenoceptors

Vandeputte, Catherine; Docherty, James R; European journal of pharmacology; vol. 457; nb. 1; (2002); p. 45 - 49, View in Reaxys 288 of 373 Effect (Pharmacological Data)

hypertensive

Species or Test-System (Pharmacological Data)

C57BL6 α2A/D-adrenoceptor knockout mouse

Sex

male and female

Route of Application

intravenous

Concentration (Pharmacological Data)

5 - 20 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in distilled water using an ultrasonic bath and diluted in normal saline (0.9 percent NaCl, w/v)

Method (Pharmacological Data)

mice anaesthetised with pentobarbitone; title comp. injected; blood pressure observed at 20 - 30 s, 1, 2, 3, 4, 5, and 10 min post injection

Results

title comp. induced sign. increase in heart rate; title comp. produced prolonged pressor response without depressor response at doses of 5 mg/kg and 20 mg/kg

Vandeputte, Catherine; Docherty, James R; European journal of pharmacology; vol. 457; nb. 1; (2002); p. 45 - 49, View in Reaxys 289 of 373 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

intracerebroventricular

Concentration (Pharmacological Data)

0.01 - 2 μg

Kind of Dosing (Pharmacological Data)

administered in increasing concentrations in volume of 2 μl over 8 s; dose per infusion

Method (Pharmacological Data)

rats trained to press two active levers to obtain water; preferred lever determined; rats allowed for 1 h to self-administer title comp. or sterile cerebrospinal fluid by pressing nonpreferred or preferred lever, resp.; number of pressings examined

Further Details (Pharmacological Data)

water allowed only for 1 h per session and then for 10 min afterwards throughout experiment; further investigations with cannabinoid agonist CP 55,940 and cannabinoid antagonist SR 141716A

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Type (Pharmacological Data)

ED50

Value of Type (Pharmacological Data)

0.87 μg

Results

0.01-1 μg/infusion of title comp. dose-dependently increased number of pressing delivering title comp. (figure); 2 μg/infusion gradual decreased title-comp.-associated pressings; effect was decreased by CP 55,940 and increased by SR 141716A

Braida, Daniela; Sala, Mariaelvina; British journal of pharmacology; vol. 136; nb. 8; (2002); p. 1089 - 1092, View in Reaxys 290 of 373 Effect (Pharmacological Data)

gene expression; inhibition of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 mg/kg

Kind of Dosing (Pharmacological Data)

daily dose; subchronic treatment

Method (Pharmacological Data)

title comp. administered for 8 days; on day 9 brain was removed and fixed; brain sections were obtained; in situ hybridization; preprotachykinin mRNA level was estimated

Further Details (Pharmacological Data)

control: saline solution, i.p.

Results

title comp. reduced preprotachykinin mRNA level in core and shell of nucleus accumbens by 21.8 and 20.5 percent, in islands of calleja by 25.2 percent, in olfactory tubercle by 9.4 percent and in bed nucleus of stria terminalis by 36 percent

Pompei, Pierluigi; Cavazzuti, Elena; Martarelli, Daniele; Pediconi, Dario; Arletti, Rossana; Lucas, Louis Ralph; Massi, Maurizio; European Journal of Pharmacology; vol. 450; nb. 3; (2002); p. 245 - 251, View in Reaxys 291 of 373 Effect (Pharmacological Data)

gene expression; inhibition of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 mg/kg

Kind of Dosing (Pharmacological Data)

daily dose; subchronic treatment

Method (Pharmacological Data)

title comp. administered for 8 days; on day 9 brain was removed and fixed; brain sections were obtained; in situ hybridization; preprotachykinin mRNA level was estimated

Further Details (Pharmacological Data)

control: saline solution, i.p.

Results

title comp. reduced preprotachykinin mRNA level in medial habenular nucleus by 24.8 percent and in postero-dorsal part of medial amygdala by 26.6 percent

gene expression; inhibition of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

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Concentration (Pharmacological Data)

5 mg/kg

Kind of Dosing (Pharmacological Data)

daily dose; subchronic treatment

Method (Pharmacological Data)

title comp. administered for 8 days; on day 9 brain was removed and fixed; brain sections were obtained; in situ hybridization; preprotachykinin mRNA level was estimated

Further Details (Pharmacological Data)

control: saline solution, i.p.

Results

title comp. increased preprotachykinin mRNA level in dorsal and ventral part of caudateputamen by 18.5 and 23.4 percent, respectively

behavioural symptoms

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 mg/kg

Kind of Dosing (Pharmacological Data)

daily dose; subchronic treatment

Method (Pharmacological Data)

title comp. administered for 8 days; 120 min after last injection social memory test was performed

Further Details (Pharmacological Data)

control: saline solution, i.p.

Results

title comp. impaired short-term working memory

antinociceptive

Species or Test-System (Pharmacological Data)

CD-1 mouse

Sex

male and female

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 - 10 mg/kg

Kind of Dosing (Pharmacological Data)

mice received repeated and intermittent administration of title comp. in saline for 3 days; injections administered in order to have 2-d interval between each day of treatment

Method (Pharmacological Data)

mice treated with title comp.; at the end of chronic treatment, 1 h after being injected with title comp., mice were assessed for pain reactivity in a hot-plate apparatus; analgesia measured as latency for fore- and hind-paw licking

Further Details (Pharmacological Data)

mice divided into three age groups during adolescence: early (28 days old), middle (38 days old) and late (52 days old); control: vehicle

Results

title comp. showed dose-dependent analgesia in middle and late adolescent mice

Morley-Fletcher, Sara; Bianchi, Mauro; Gerra, Gilberto; Laviola, Giovanni; European journal of pharmacology; vol. 448; nb. 1; (2002); p. 31 - 38, View in Reaxys 295 of 373 Effect (Pharmacological Data) Species or Test-System (Pharmacological Data)

behavioural symptoms CD-1 mouse

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Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 - 10 mg/kg

Kind of Dosing (Pharmacological Data)

mice received repeated and intermittent administration of title comp. in saline for 3 days; injections administered in order to have 2-d interval between each day of treatment

Method (Pharmacological Data)

mice divided to pairs of same age-drug treatment and placed in test arena for 15 min; aggressive items of behaviour, environment exploration, social investigation, self-grooming and freezing assessed

Further Details (Pharmacological Data)

mice received title comp. during early (28 days old), middle (38 days old) or late (52 days old) adolescence; assay performed in adult (80 days old) mice; control: vehicle

Results

title comp. increased time spent in environment exploration and social investigation but decreased freezing in mice treated during early adolescence and decreased self-grooming in all groups; title comp. had no effect on aggressive items of behaviour

Morley-Fletcher, Sara; Bianchi, Mauro; Gerra, Gilberto; Laviola, Giovanni; European journal of pharmacology; vol. 448; nb. 1; (2002); p. 31 - 38, View in Reaxys 296 of 373 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

CD-1 mouse

Sex

male and female

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 - 10 mg/kg

Kind of Dosing (Pharmacological Data)

mice received repeated and intermittent administration of title comp. in saline for 3 days; injections administered in order to have 2-d interval between each day of treatment

Method (Pharmacological Data)

mice treated with title comp.; novelty-seeking test including 3 days of familiarisation and 1 day of testing performed

Further Details (Pharmacological Data)

mice received title comp. during early (28 days old), middle (38 days old) or late (52 days old) adolescence; assay performed in adult (80 days old) mice; mice challenged with title comp. at the day of testing; control: vehicle

Results

title comp. at highest dose tested increased locomotor activity in male mice treated during early adolescence; mice challenged with title comp. showed increased novelty seeking and locomotor activity in all age groups

Morley-Fletcher, Sara; Bianchi, Mauro; Gerra, Gilberto; Laviola, Giovanni; European journal of pharmacology; vol. 448; nb. 1; (2002); p. 31 - 38, View in Reaxys 297 of 373 Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

CD-1 mouse

Sex

male and female

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 - 10 mg/kg

Kind of Dosing (Pharmacological Data)

mice received repeated and intermittent administration of title comp. in saline for 3 days; injections administered in order to have 2-d interval between each day of treatment

Method (Pharmacological Data)

mice challenged with title comp. and sacrificed 1 h after injection; amounts of serotonin and its metabolic products in hypothalamus evaluated by liquid chromatography

Further Details (Pharmacological Data)

mice received title comp. during early (28 days old), middle (38 days old) or late (52 days old) adolescence; assay performed in adult (80 days old) mice; control: vehicle

Results

challenge with title comp. increased levels in hypothalamic serotonin release and concomitant reduction of 5-hydroxyindol-acetic levels; chronic treatment with 5 mg/kg during middle and late adolescence decreased indoleamine levels in adult mice

Copyright ÂŠ 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. ReaxysÂŽ and the ReaxysÂŽ trademark are owned and protected by Reed Elsevier Properties SA and used under license.

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Morley-Fletcher, Sara; Bianchi, Mauro; Gerra, Gilberto; Laviola, Giovanni; European journal of pharmacology; vol. 448; nb. 1; (2002); p. 31 - 38, View in Reaxys 298 of 373 Effect (Pharmacological Data)

muscle contraction; effect on

Species or Test-System (Pharmacological Data)

Wistar rat right ventricle

Sex

male

Concentration (Pharmacological Data)

10 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. dissolved in distilled water

Method (Pharmacological Data)

ventricular strips were set up between platinum electrodes and isometric force transducer under 2 g tension and paced at frequency of 1 Hz; equilibrated; NA added; tissue exposed to title comp. for 30 min; CRC to NA recorded in presence of title comp.

Further Details (Pharmacological Data)

controls: NA (noradrenaline), vehicle; ref.: cocaine; CRC: concentration-response curve

Results

maximum contractile effect of NA was not significantly affected by title comp. (215.9/213.4 percent by vehicle/title comp., respectively); diagram

Cleary, Linda; Buber, Robert; Docherty, James R.; European Journal of Pharmacology; vol. 451; nb. 3; (2002); p. 303 - 308, View in Reaxys 299 of 373 Effect (Pharmacological Data)

muscle contraction; increase of

Species or Test-System (Pharmacological Data)

Wistar rat right ventricle

Sex

male

Concentration (Pharmacological Data)

10 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. dissolved in distilled water

Method (Pharmacological Data)

ventricular strips were set up between platinum electrodes and isometric force transducer under 2 g tension and paced at a frequency of 1 Hz; equilibrated; NA added; tissue exposed to title comp. for 30 min; contractile potency of NA determined

Further Details (Pharmacological Data)

controls: NA (noradrenaline), vehicle; ref.: cocaine

Type (Pharmacological Data)

pD2

Value of Type (Pharmacological Data)

6.42 dimensionless

Results

title comp. significantly increased the potency of noradrenaline as compared to vehicle; table, diagram

Cleary, Linda; Buber, Robert; Docherty, James R.; European Journal of Pharmacology; vol. 451; nb. 3; (2002); p. 303 - 308, View in Reaxys 300 of 373 Effect (Pharmacological Data)

muscle contraction; effect on

Species or Test-System (Pharmacological Data)

Wistar rat right ventricle

Sex

male

Concentration (Pharmacological Data)

10 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. dissolved in distilled water

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Method (Pharmacological Data)

ventricular strips were set up between platinum electrodes and isometric force transducer under 2 g tension and paced at frequency of 1 Hz; equilibrated; IS added; tissue exposed to title comp. for 30 min; CRC to IS recorded in presence of title comp.

Further Details (Pharmacological Data)

controls: IS (isoprenaline), vehicle; ref.: cocaine; CRC: concentration-response curve

Results

maximum contractile effect of IS was not significantly affected by title comp. (269.7/252.4 percent of control by vehicle/title comp., respectively); diagram

Cleary, Linda; Buber, Robert; Docherty, James R.; European Journal of Pharmacology; vol. 451; nb. 3; (2002); p. 303 - 308, View in Reaxys 301 of 373 Effect (Pharmacological Data)

muscle contraction; effect on

Species or Test-System (Pharmacological Data)

Wistar rat right ventricle

Sex

male

Concentration (Pharmacological Data)

10 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. dissolved in distilled water

Method (Pharmacological Data)

ventricular strips were set up between platinum electrodes and isometric force transducer under 2 g tension and paced at a frequency of 1 Hz; equilibrated; IS added; tissue exposed to title comp. for 30 min; contractile potency of IS determined

Further Details (Pharmacological Data)

controls: IS (isoprenaline), vehicle; ref.: cocaine

Type (Pharmacological Data)

pD2

Value of Type (Pharmacological Data)

7.08 dimensionless

Results

title comp. did not significantly affect the response to IS as compared to vehicle; table, diagram

Cleary, Linda; Buber, Robert; Docherty, James R.; European Journal of Pharmacology; vol. 451; nb. 3; (2002); p. 303 - 308, View in Reaxys 302 of 373 Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

K-25 human liver microsomes

Concentration (Pharmacological Data)

0.613 - 500 μmol/l

Method (Pharmacological Data)

0.4 mg/ml microsomal protein incubated with title comp., 0.1 mol/l KH2PO4 buffer (pH 7.4), 30 units SOD and 1 mmol/l NADPH (37 deg C, 25 min); reaction stopped by 70 percent perchloric acid; centrifuged; metabolite levels in supernatant analyzed by HPLC

Further Details (Pharmacological Data)

reference: dextromethorphan; K-25 liver (K25) genotyped as cytochrome P450 2D6*1/*1 was used in this study; SOD: superoxide dismutase

Results

Km (μmol/l), Vmax (nmol/mg/min), intrinsic clearance (ml/mg/min) of title comp. metabolism at site 1 and 2 were 1.5, 0.007, 0.005 and 607.6, 0.04, 0.0007, resp.; intrinsic clearance of ref. was ca. 6.5-fold higher than that of title comp.; table

Metabolite XRN (Pharmacological Data)

3251333

Metabolite (Pharmacological Data)

(+/-)-DHMA

Ramamoorthy, Yamini; Yu, Ai-ming; Suh, Nina; Haining, Robert L.; Tyndale, Rachel F.; Sellers, Edward M.; Biochemical Pharmacology; vol. 63; nb. 12; (2002); p. 2111 - 2119, View in Reaxys 303 of 373 Effect (Pharmacological Data)

biotransformation

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Species or Test-System (Pharmacological Data)

human liver microsomes

Concentration (Pharmacological Data)

0.613 - 500 μmol/l

Method (Pharmacological Data)

0.4 mg/ml pooled microsomal protein incubated with title comp., 0.1 mol/l KH2PO4 buffer (pH 7.4), 30 units SOD and 1 mmol/l NADPH (37 deg C, 25 min); reaction stopped by 70 percent perchloric acid; centrifuged; metabolite levels in supernatant analyzed by HPLC

Further Details (Pharmacological Data)

SOD: superoxide dismutase

Results

Km (μmol/l), Vmax (nmol/mg/min), intrinsic clearance (ml/mg/min) of title comp. metabolism at site 1 and 2 were 2.0, 0.005, 0.003 and 398.5, 0.06, 0.0001, respectively; table

Metabolite XRN (Pharmacological Data)

3251333

Metabolite (Pharmacological Data)

(+/-)-DHMA

biotransformation

Species or Test-System (Pharmacological Data)

cDNA-expressing CYP2D6 microsomes from human lymphoblasts

Method (Pharmacological Data)

0.48 mg/ml microsomal protein incubated with title comp., 0.1 mol/l KH2PO4 buffer (pH 7.4), 30 units SOD and 1 mmol/l NADPH (37 deg C, 25 min); reaction stopped by 70 percent perchloric acid; centrifuged; metabolite levels in supernatant analyzed by HPLC

Further Details (Pharmacological Data)

CYP2D6: cytochrome P450 2D6; SOD: superoxide dismutase

Results

title comp. metabolite formed; Km and Vmax values were 4.1 μmol/l and 0.25 nmol/mg/min, respectively

Metabolite XRN (Pharmacological Data)

3251333

Metabolite (Pharmacological Data)

(+/-)-DHMA

biotransformation

Species or Test-System (Pharmacological Data)

microsomes from Trichoplusia ni expressing CYP2D6.1

Concentration (Pharmacological Data)

1.95 - 500 μmol/l

Method (Pharmacological Data)

enzyme incubated with NADPH reductase (RT, 15 min); DLPTC added; incubated (RT, 10 min); incubated with title comp., buffer, SOD (5 min); reaction initiated by NADPH; incub. (37 deg C, 25 min); reaction stopped; centrifuged; top layer analyzed by HPLC

Further Details (Pharmacological Data)

reference: dextromethorphan; buffer: 0.1 mol/l KH2PO4 buffer (pH 7.4); RT: room temperature; CYP2D6.1: cytochrome P450 2D6.1; DLPTC: L-α-phosphatidylcholine, dilauroyl; SOD: superoxide dismutase

Results

Km, Vmax and intrinsic clearance values were 6.2 μmol/l, 167.5E-5 nmol/pmol/min and 30.3E-5 ml/pmol 2D6/min, respectively; enzyme displayed monophasic kinetics; table

Metabolite XRN (Pharmacological Data)

3251333

Metabolite (Pharmacological Data)

(+/-)-DHMA

Ramamoorthy, Yamini; Yu, Ai-ming; Suh, Nina; Haining, Robert L.; Tyndale, Rachel F.; Sellers, Edward M.; Biochemical Pharmacology; vol. 63; nb. 12; (2002); p. 2111 - 2119, View in Reaxys

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306 of 373 Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

microsomes from Trichoplusia ni expressing CYP2D6.2

Concentration (Pharmacological Data)

1.95 - 500 μmol/l

Method (Pharmacological Data)

enzyme incubated with NADPH reductase (RT, 15 min); DLPTC added; incubated (RT, 10 min); incubated with title comp., buffer, SOD (5 min); reaction initiated by NADPH; incub. (37 deg C, 40 min); reaction stopped; centrifuged; top layer analyzed by HPLC

Further Details (Pharmacological Data)

reference: dextromethorphan; buffer: 0.1 mol/l KH2PO4 buffer (pH 7.4); RT: room temperature; CYP2D6.2: cytochrome P450 2D6.2; DLPTC: L-α-phosphatidylcholine, dilauroyl; SOD: superoxide dismutase

Results

Km, Vmax and intrinsic clearance values were 10.3 μmol/l, 19E-5 nmol/pmol/min and 1.8E-5 ml/pmol 2D6/min, respectively; enzyme displayed biphasic kinetics; table

Metabolite XRN (Pharmacological Data)

3251333

Metabolite (Pharmacological Data)

(+/-)-DHMA

biotransformation

Species or Test-System (Pharmacological Data)

microsomes from Trichoplusia ni expressing CYP2D6.17

Concentration (Pharmacological Data)

1.95 - 500 μmol/l

Method (Pharmacological Data)

enzyme incubated with NADPH reductase (RT, 15 min); DLPTC added; incubated (RT, 10 min); incubated with title comp., buffer, SOD (5 min); reaction initiated by NADPH; incub. (37 deg C, 40 min); reaction stopped; centrifuged; top layer analyzed by HPLC

Further Details (Pharmacological Data)

reference: dextromethorphan; buffer: 0.1 mol/l KH2PO4 buffer (pH 7.4); RT: room temperature; CYP2D6.17: cytochrome P450 2D6.17; DLPTC: L-α-phosphatidylcholine, dilauroyl; SOD: superoxide dismutase

Results

Km, Vmax and intrinsic clearance values were 3.5 μmol/l, 7.5E-5 nmol/pmol/min and 2.6E-5 ml/pmol 2D6/min, respectively; enzyme displayed biphasic kinetics; table, figure

Metabolite XRN (Pharmacological Data)

3251333

Metabolite (Pharmacological Data)

(+/-)-DHMA

biotransformation

Species or Test-System (Pharmacological Data)

microsomes from Trichoplusia ni expressing CYP2D6.10

Concentration (Pharmacological Data)

1.95 - 500 μmol/l

Method (Pharmacological Data)

enzyme incubated with NADPH reductase (RT, 15 min); DLPTC added; incubated (RT, 10 min); incubated with title comp., buffer, SOD (5 min); reaction initiated by NADPH; incub. (37 deg C, 40 min); reaction stopped; centrifuged; top layer analyzed by HPLC

Further Details (Pharmacological Data)

reference: dextromethorphan; buffer: 0.1 mol/l KH2PO4 buffer (pH 7.4); RT: room temperature; CYP2D6.10: cytochrome P450 2D6.10; DLPTC: L-α-phosphatidylcholine, dilauroyl; SOD: superoxide dismutase

Results

Km, Vmax and intrinsic clearance values were 18.7 μmol/l, 4.4E-5 nmol/pmol/min and 0.2E-5 ml/pmol 2D6/min, respectively; enzyme displayed biphasic kinetics; table

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Metabolite XRN (Pharmacological Data)

3251333

Metabolite (Pharmacological Data)

(+/-)-DHMA

biotransformation

Species or Test-System (Pharmacological Data)

human liver microsomes expressing CYP2D6*1/*1

Concentration (Pharmacological Data)

0.613 - 500 μmol/l

Method (Pharmacological Data)

0.4 mg/ml microsomal protein incubated with title comp., 0.1 mol/l KH2PO4 buffer (pH 7.4), 30 units SOD and 1 mmol/l NADPH (37 deg C, 15 min); reaction stopped by 70 percent perchloric acid; centrifuged; metabolite levels in supernatant analyzed by HPLC

Further Details (Pharmacological Data)

reference: dextromethorphan; CYP2D6: cytochrome P450 2D6; HL-series liver (HL-160, HL-139) were used; SOD: superoxide dismutase

Results

Km, Vmax and intrinsic clearance of title comp. were 0.9 μmol/l, 0.01 nmol/mg/min and 0.02 ml/mg/min, respectively; table

Metabolite XRN (Pharmacological Data)

3251333

Metabolite (Pharmacological Data)

(+/-)-DHMA

biotransformation

Species or Test-System (Pharmacological Data)

human liver microsomes expressing CYP2D6*1/*10

Concentration (Pharmacological Data)

0.613 - 500 μmol/l

Method (Pharmacological Data)

Further Details (Pharmacological Data)

reference: dextromethorphan; CYP2D6: cytochrome P450 2D6; HL-series liver (HL-135, HL-132) were used; SOD: superoxide dismutase

Results

Km, Vmax and intrinsic clearance of title comp. were 1.0 μmol/l, 0.01 nmol/mg/min and 0.01 ml/mg/min, respectively; table

Metabolite XRN (Pharmacological Data)

3251333

Metabolite (Pharmacological Data)

(+/-)-DHMA

Ramamoorthy, Yamini; Yu, Ai-ming; Suh, Nina; Haining, Robert L.; Tyndale, Rachel F.; Sellers, Edward M.; Biochemical Pharmacology; vol. 63; nb. 12; (2002); p. 2111 - 2119, View in Reaxys 311 of 373

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

human liver microsomes expressing CYP2D6*2/*10

Concentration (Pharmacological Data)

0.613 - 500 μmol/l

Method (Pharmacological Data)

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Further Details (Pharmacological Data)

reference: dextromethorphan; CYP2D6: cytochrome P450 2D6; HL-series liver (HL-142, HL-133) were used; SOD: superoxide dismutase

Results

Km, Vmax and intrinsic clearance of title comp. were 0.7 μmol/l, 0.01 nmol/mg/min and 0.02 ml/mg/min, respectively; table

Metabolite XRN (Pharmacological Data)

3251333

Metabolite (Pharmacological Data)

(+/-)-DHMA

biotransformation

Species or Test-System (Pharmacological Data)

human liver microsomes expressing CYP2D6*1/*2

Concentration (Pharmacological Data)

0.613 - 500 μmol/l

Method (Pharmacological Data)

Further Details (Pharmacological Data)

reference: dextromethorphan; CYP2D6: cytochrome P450 2D6; HL-series liver (HL-143, HL-156) were used; SOD: superoxide dismutase

Results

Km, Vmax and intrinsic clearance of title comp. were 1.6 μmol/l, 0.007 nmol/mg/min and 0.004 ml/mg/min, respectively; table

Metabolite XRN (Pharmacological Data)

3251333

Metabolite (Pharmacological Data)

(+/-)-DHMA

behavioural symptoms

Species or Test-System (Pharmacological Data)

albino Wistar rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. was diluted in 0.9 percent saline and 5 mg/kg administered every hour for 4 h for 2 consecutive days

Method (Pharmacological Data)

rats admin. with title comp.; immediately after dosing, placed in standard operant chambers fitted with infrared detectors; movements of head and body as well as gross locomotion counted

Further Details (Pharmacological Data)

control: vehicle

Results

title comp.-treated rats displayed significantly greater overall locomotor activity on day 1 and day 2; title comp. group had signif. greater activity in hours 2, 3 and 4 of testing on both day 1 and 2; fig.

Gurtman, Clint G; Morley, Kirsten C; Li, Kong M; Hunt, Glenn E; McGregor, Iain S; European journal of pharmacology; vol. 446; nb. 1-3; (2002); p. 89 - 96, View in Reaxys 314 of 373 Effect (Pharmacological Data) Species or Test-System (Pharmacological Data)

hyperthermic albino Wistar rat

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Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. was diluted in 0.9 percent saline and 5 mg/kg administered for 4 h for 2 consecutive days

Method (Pharmacological Data)

rats admin. with title comp.; body temperature measured after each hour of dosing

Further Details (Pharmacological Data)

control: vehicle

Results

title comp.-treated rats had higher overall body temperature than controls on both day 1 and day 2 of administration; title comp.-treated group had significantly greater temperature in hours 2, 3 and 4 of testing on both day 1 and 2; fig.

Gurtman, Clint G; Morley, Kirsten C; Li, Kong M; Hunt, Glenn E; McGregor, Iain S; European journal of pharmacology; vol. 446; nb. 1-3; (2002); p. 89 - 96, View in Reaxys 315 of 373 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

albino Wistar rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. was diluted in 0.9 percent saline and 5 mg/kg administered every hour for 4 h for 2 consecutive days

Method (Pharmacological Data)

rats admin. with title comp.; after 4 weeks, placed in wooden hide box and tested for emergence for 5 min; latency of rats to emerge from hide box and duration of time spent in open field recorded

Further Details (Pharmacological Data)

control: vehicle

Results

title comp.-treated rats had longer latency to emerge from hide box and spent less time in open field than control; table

Gurtman, Clint G; Morley, Kirsten C; Li, Kong M; Hunt, Glenn E; McGregor, Iain S; European journal of pharmacology; vol. 446; nb. 1-3; (2002); p. 89 - 96, View in Reaxys 316 of 373 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

albino Wistar rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. was diluted in 0.9 percent saline and 5 mg/kg administered every hour for 4 h for 2 consecutive days

Method (Pharmacological Data)

rats admin. with title comp.; after 6 weeks, tested for social interaction for 10 min across three consecutive days with each rat tested with different partner on first two days

Further Details (Pharmacological Data)

control: vehicle

Results

title comp.-treated rats spent significantly less time in social interaction than control; showed fewer total interactions than control; table

Gurtman, Clint G; Morley, Kirsten C; Li, Kong M; Hunt, Glenn E; McGregor, Iain S; European journal of pharmacology; vol. 446; nb. 1-3; (2002); p. 89 - 96, View in Reaxys

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317 of 373 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

albino Wistar rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. was diluted in 0.9 percent saline and 5 mg/kg administered every hour for 4 h for 2 consecutive days

Method (Pharmacological Data)

rats admin. with title comp.; after 9 weeks, tested on elevated plus-maze in 5-min test; time spent on the open arms, time spent on closed arm and total number of arm entries were monitored

Further Details (Pharmacological Data)

control: vehicle

Results

title comp.-treated rats spent less time on open arms of plus-maze and more time in closed arms than controls; there was no difference in total number of arm entries between title comp.-treated rats and control; table

Gurtman, Clint G; Morley, Kirsten C; Li, Kong M; Hunt, Glenn E; McGregor, Iain S; European journal of pharmacology; vol. 446; nb. 1-3; (2002); p. 89 - 96, View in Reaxys 318 of 373 Effect (Pharmacological Data)

transmitter release; inhibition of

Species or Test-System (Pharmacological Data)

albino Wistar rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. was diluted in 0.9 percent saline and 5 mg/kg administered every hour for 4 h for 2 consecutive days

Method (Pharmacological Data)

rats admin. with title comp.; after 10 weeks, decapitated; olfactory bulb, caudate-putamen, amygdala and anterodorsal part of hippocampus dissected; homogenized; dopamine, 5hydroxyindoleacetic acid, 5-hydroxytryptamine levels detd. by HPLC with ECD

Further Details (Pharmacological Data)

control: vehicle; ECD: electro-chemical detection

Results

title comp.-treated rats had signif. less 5-hydroxytryptamine and 5-hydroxyindoleacetic acid than controls in amygdala, hippocampus and caudate-putamen; no signif. difference observed with respect to dopamine; table

Gurtman, Clint G; Morley, Kirsten C; Li, Kong M; Hunt, Glenn E; McGregor, Iain S; European journal of pharmacology; vol. 446; nb. 1-3; (2002); p. 89 - 96, View in Reaxys 319 of 373 Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

Homo sapiens

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

100 mg

Exposure Period (Pharmacological Data)

24 h

Method (Pharmacological Data)

4 healthy subjects (25.5 years, 69.5 kg, 182.0 cm, all recreational users of title comp.); blood sampled before title comp. admin. at 20, 40, 60, 90 min and at 2, 3, 4, 6, 8, 10, 24 h after admin.; GC/MS or HPLC/ED

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Further Details (Pharmacological Data)

Cmax: maximal conc.; Ka: formation rate constant; Ke: elimination constant; AUC0-24: area under plasma conc. of title comp. vs time curve; HHMA: 3,4-dihydroxymethamphetamine; HMMA: 4-hydroxy-3-methoxymethamphetamine

Results

Cmax = 181.6, 307.1, 154.5 ng/mL; Ka = 2.5, 2.1, 5.3 h-1; Ke = 0.099, 0.084, 0.063 h-1; T1/2 = 7.1, 8.3, 13.4 h; AUC0-24 = 1465.9, 3190.9, 1990.94 ng/mL*h for title comp., HMMA, HHMA, respectively; HHMA is the main metabolite; table

Comment (Pharmacological Data)

Further metabolite(s)

Metabolite XRN (Pharmacological Data)

3261956; 3251333; 150196

Metabolite (Pharmacological Data)

4-Hydroxy-3-methoxymethamphetamine; (+/-)-DHMA; 3,4-methylenedioxyamphetamine

Segura; Ortuno; Farre; Mc Lure; Pujadas; Pizarro; Llebaria; Joglar; Roset; De la Torre; Chemical Research in Toxicology; vol. 14; nb. 9; (2001); p. 1203 - 1208, View in Reaxys 320 of 373 Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 mg/kg

Exposure Period (Pharmacological Data)

Method (Pharmacological Data)

animals (weights 200-250 g) pretreated with acivicin (18 mg/kg, i.p.) 20 min prior title comp. administration; 12-h light/dark cycle; 72 deg F; neurotransmitter analysis of brain tissues

Results

inhibition of γ-glutamyl transpeptidase; thioether metabolites contribution (diagrams)

Bai; Jones; Lau; Monks; Chemical Research in Toxicology; vol. 14; nb. 7; (2001); p. 863 - 870, View in Reaxys 321 of 373 Effect (Pharmacological Data)

narcotic

Species or Test-System (Pharmacological Data)

Long-Evans rats

Sex

male

Route of Application

intravenous

Concentration (Pharmacological Data)

0.032 - 10 mg/kg

Method (Pharmacological Data)

rats (280-450 g) trained to respond for food pellets and water at fixed ratio 1 (FR1) schedule of reinforcement; the operant chamber has 2 levers: for food (and later for i.v. self-administration of drugs) and water

Further Details (Pharmacological Data)

drug naive and cocaine-trained animals used

Results

reinforcing effect of title comp. did not differ between drug-naive and cocaine-trained animals; title comp. sensitized animals to its own rate-increasing effect; after cocaine, title comp. no carryover of cocaine's reinforcing effect

Ratzenboeck, Elisabeth; Saria, Alois; Kriechbaum, Norbert; Zernig, Gerald; Pharmacology; vol. 62; nb. 3; (2001); p. 138 - 144, View in Reaxys 322 of 373 Effect (Pharmacological Data) Species or Test-System (Pharmacological Data)

agonist HEK293 cells expressing rTAR1

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Concentration (Pharmacological Data)

Ca. 1E-09 - 1E-05 mol/l

Method (Pharmacological Data)

cells incubated in KRH with 100 μmol/l 3-isobutyl-1-methylxanthine and title comp. for 1 h at 37 deg C; cAMP content measured using competitive binding of <3H>cAMP to a cAMPbinding protein

Further Details (Pharmacological Data)

HEK: human embryonic kidney; rTAR1: rat trace amine receptor 1; reference comp.: forskolin; KRH: Krebs-Ringer-HEPES buffer

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

1700 nmol/l

Results

title comp. induced cAMP production acting as agonist (diagram)

Bunzow; Sonders; Arttamangkul; Harrison; Zhang; Quigley; Darland; Suchland; Pasumamula; Kennedy; Olson; Magenis; Amara; Grandy; Molecular Pharmacology; vol. 60; nb. 6; (2001); p. 1181 - 1188, View in Reaxys 323 of 373 Effect (Pharmacological Data)

immunomodulator

Species or Test-System (Pharmacological Data)

human

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

100 mg

Kind of Dosing (Pharmacological Data)

alone: single dose; in combination with ethanol: single dose, EtOH 0.8 mg/kg 0.5 h later

Method (Pharmacological Data)

double-blind, double-dummy, randomized, crossover, 4*4 Latin square study; over 24 h after title comp. administration blood sampled, detd.: plasma title comp. and EtOH by GC, cortisol and cytokines by ELISA, lymphocyte subsets by staining, cytometry

Further Details (Pharmacological Data)

6 healthy title comp. users, 19-36 years, smokers (<20 cigarettes daily), phenotyped for CYP2D6 by dextromethorphan: extensive metabolizers; effect of title comp. alone or in combination with ethanol studied

Results

acute title comp. caused time-dependent immune dysfunction and cortisol stimulation kinetics parallel with title comp. conc. in plasma; num. tables, diagrams of lymphocyte subsets, cortisol, IL-1β, -2, -4, -6, -10, TNF-α, IFN-γ, TGF-β1 levels

neurotoxicity

Species or Test-System (Pharmacological Data)

Dark Agouti rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

15 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in saline (0.9 percent NaCl); given in volume of 1 ml/kg

Method (Pharmacological Data)

7 days after treatment, rats sacrificed; 5-HT and 5-HIAA in cerebral tissue measured by HPLC with amperometric detector; <3H>paroxetine binding (90 min, room temperature) studied in cortical tissue

Further Details (Pharmacological Data)

5-HT: 5-hydroxytryptamine; 5-HIAA: 5-hydroxyindoleacetic acid

Results

title comp. markedly decreased 5-HT and 5-HIAA concentration in cortex, hippocampus and striatum and reduced cortical <3H>paroxetine binding

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Sanchez; Camarero; Esteban; Peter; Green; Colado; British Journal of Pharmacology; vol. 134; nb. 1; (2001); p. 46 - 57, View in Reaxys 325 of 373 Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

used as hydrochloride; dissolved in 1 ml 0.9 percent saline; given twice daily for 4 consecutive days

Method (Pharmacological Data)

after 1, 7, 14 or 21 days of recovery after title comp. treatment, brain synaptosomal fraction obtained and incubated with <3H>5-HT at 37 deg C for 4 min; radioactivity measured by liquid scintillation spectroscopy

Further Details (Pharmacological Data)

5-HT: 5-hydroxytryptamine

Results

title comp. significantly reduced maximum rate of 5-HT uptake (12.9 percent at 24 h, then recovered: 38.1 percent at 7 days, 76.3 percent at 21 days after title comp. treatment)

Cannon, Dara M.; Keenan, Alan K.; Guiry, Patrick J.; Buon, Christophe; Baird, Alan W.; McBean, Gethin J.; British Journal of Pharmacology; vol. 134; nb. 7; (2001); p. 1455 - 1460, View in Reaxys 326 of 373 Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Wistar rat brain synaptosomes

Sex

male

Concentration (Pharmacological Data)

100 μmol/l

Kind of Dosing (Pharmacological Data)

used as hydrochloride

Method (Pharmacological Data)

synaptosomes incubated with 100 nmol/l <3H>5-HT at 37 deg C for 4 min; radioactivity measured by liquid scintillation spectroscopy

Further Details (Pharmacological Data)

5-HT: 5-hydroxytryptamine

Results

title comp. significantly reduced rate of 5-HT transport to 9 percent of untreated control

neurotoxicity

Species or Test-System (Pharmacological Data)

Wistar rat thoracic aorta

Sex

male

Concentration (Pharmacological Data)

100 μmol/l

Kind of Dosing (Pharmacological Data)

used as hydrochloride

Method (Pharmacological Data)

synaptosomes incubated with 1000 nmol/l <3H>5-HT at 37 deg C for 5 min; radioactivity measured by liquid scintillation spectroscopy

Further Details (Pharmacological Data)

5-HT: 5-hydroxytryptamine

Comment (Pharmacological Data)

No effect

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vasotoxic

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

used as hydrochloride; dissolved in 1 ml 0.9 percent saline; given twice daily for 4 consecutive days

Method (Pharmacological Data)

after 1 day of recovery after title comp. treatment, thoracic aortic rings prepared and incubated with <3H>5-HT at 37 deg C for 5 min; radioactivity measured by liquid scintillation spectroscopy

Further Details (Pharmacological Data)

5-HT: 5-hydroxytryptamine

Comment (Pharmacological Data)

No effect

vasotoxic

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

used as hydrochloride; dissolved in 1 ml 0.9 percent saline; given twice daily for 4 consecutive days

Method (Pharmacological Data)

after 1, 7, 14 or 21 days of recovery after title comp. treatment, descending thoracic aortae dissected, attached to Grass force displacement transducer at 37 deg C under basal tension of 1.3 g; changes in isometric tension to 5-HT recorded

Further Details (Pharmacological Data)

5-HT: 5-hydroxytryptamine

Results

title comp. significantly reduced maximum contraction induced by 5-HT in aortae isolated 1 and 7 days after title comp. treatment

enzyme; inhib. of

Species or Test-System (Pharmacological Data)

human lymphoblastoid cell line expressing human CYP2D6

Method (Pharmacological Data)

effect of title comp. on cytochrome P450 2D6 mediated O-demethylation of 7-methoxy-4(aminomethyl)coumarin in pH 7.4 phosphate buffer at 37 deg C; 7-hydroxy-4-(aminomethyl)coumarin determined by fluorescence measurement

Further Details (Pharmacological Data)

CYP2D6 = cytochrome P450 2D6

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

0.92 μmol/l

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Venhorst, Jennifer; Onderwater, Rob C.A.; Meerman, John H.N.; Vermeulen, Nico P.E.; Commandeur, Jan N.M.; European Journal of Pharmaceutical Sciences; vol. 12; nb. 2; (2000); p. 151 - 158, View in Reaxys 331 of 373 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Wistar albino rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

1.25 - 5 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.9 percent saline

Method (Pharmacological Data)

rats treated with title comp.; 20 min later subjected to emergence test; emergence latency and frequency, duration of time spent in open field and defecation observed for 5 min

Further Details (Pharmacological Data)

control: vehicle

Results

title comp. significantly decreased frequency of emergence and amount of time spent in open field, increased emergence latency and amount of defecation (table)

Morley, Kirsten C; McGregor, Iain S; European Journal of Pharmacology; vol. 408; nb. 1; (2000); p. 41 - 49, View in Reaxys 332 of 373 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Wistar albino rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

1.25 - 5 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.9 percent saline

Method (Pharmacological Data)

rats treated with title comp.; 25 min later subjected to elevated plus-maze test; open and closed arm times and number of open and closed entries recorded during 5 min

Further Details (Pharmacological Data)

control: vehicle

Results

title comp. significantly decreased amount of time spent in open arm and total arm entries at all doses, increased amount of time spent in closed arm at doses 2.5 and 5 mg/kg (figure)

Morley, Kirsten C; McGregor, Iain S; European Journal of Pharmacology; vol. 408; nb. 1; (2000); p. 41 - 49, View in Reaxys 333 of 373 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Wistar albino rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

1.25 - 5 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.9 percent saline

Method (Pharmacological Data)

rats treated with title comp.; 30 min later subjected to cat odor avoidance test; amount of time in hide box and close vicinity to cat collar recorded during 20 min

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Further Details (Pharmacological Data)

control: vehicle

Results

title comp. significantly decreased time spent in close vicinity to cat collar at dose 5 mg/kg and had no effect on time spent in hide box (table)

Morley, Kirsten C; McGregor, Iain S; European Journal of Pharmacology; vol. 408; nb. 1; (2000); p. 41 - 49, View in Reaxys 334 of 373 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Wistar albino rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

1.25 - 5 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.9 percent saline

Method (Pharmacological Data)

rats treated with title comp.; 50 min later subjected to locomotor activity test; locomotor activity observed during 60 min

Further Details (Pharmacological Data)

control: vehicle

Results

title comp. significantly increased locomotor activity during 20 - 60 min at dose 5 mg/kg (figure)

Morley, Kirsten C; McGregor, Iain S; European Journal of Pharmacology; vol. 408; nb. 1; (2000); p. 41 - 49, View in Reaxys 335 of 373 Effect (Pharmacological Data)

anxiolytic

Species or Test-System (Pharmacological Data)

Wistar albino rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

1.25 - 5 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.9 percent saline

Method (Pharmacological Data)

rats treated with title comp.; 20 min later subjected to social interaction test; social interaction (sniffing, adjacent lying, following, crawling under/over, mutual grooming), aggressive behaviours and number of squares crossed recorded during 10 min

Further Details (Pharmacological Data)

control: vehicle

Results

title comp. significantly increased time spent in social interaction and number of squares crossed at dose 5 mg/kg and decreased aggressive behaviours at all doses (figure)

Morley, Kirsten C; McGregor, Iain S; European Journal of Pharmacology; vol. 408; nb. 1; (2000); p. 41 - 49, View in Reaxys 336 of 373 Effect (Pharmacological Data)

anxiolytic

Species or Test-System (Pharmacological Data)

Wistar albino rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

1.25 - 5 mg/kg

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Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.9 percent saline

Method (Pharmacological Data)

rats treated with title comp.; subjected to footshock-induced ultrasonic vocalization test; ultrasonic vocalizations recorded after receiving of 1 mA shock of 1 s duration at initial 10min shock period and second 10-min post-shock period

Further Details (Pharmacological Data)

control: vehicle

Results

title comp. significantly decreased ultrasonic vocalizations during 10-min shock period at dose 5 mg/kg and had no effect during post-shock period (table)

Morley, Kirsten C; McGregor, Iain S; European Journal of Pharmacology; vol. 408; nb. 1; (2000); p. 41 - 49, View in Reaxys 337 of 373 Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

Dark-Agouti rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 mg/kg

Kind of Dosing (Pharmacological Data)

daily dose

Method (Pharmacological Data)

rats with shaved back hair administered with title comp. for 10 days; newly growing back hair collected 28 days after first injection; title comp. conc. determined by gas chromatography-mass spectrometry analysis

Results

93.4 ng/mg title comp. found in hair of treated rats (table, figure)

Nakahara, Yuji; Hanajiri, Ruri; Life Sciences; vol. 66; nb. 7; (2000); p. 563 - 574, View in Reaxys 338 of 373 Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

Dark-Agouti rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 mg/kg

Method (Pharmacological Data)

rats administered with title comp.; blood collected 5-360 min after injection; title comp. conc. determined by gas chromatography-mass spectrometry analysis

Further Details (Pharmacological Data)

Cmax: maximal concentration; Tmax: time of maximum concentration; AUC: area under curve

Results

title comp. found in rat plasma with Cmax: 977 ng/ml, Tmax: 15 min and AUC: 121.2 μg min/ml (table, figure)

Nakahara, Yuji; Hanajiri, Ruri; Life Sciences; vol. 66; nb. 7; (2000); p. 563 - 574, View in Reaxys 339 of 373 Effect (Pharmacological Data)

acute toxicity other

Species or Test-System (Pharmacological Data)

Homo sapiens, human

Method (Pharmacological Data)

53-year-old psychiatrist with a history of gastritis and unidentified platelet disorder; suicidal overdose title comp.

Results

12 h after ingestion of title comp. the patient developed hyperthermia (107.2 deg F) with evidence of rhabdomyolysis, acute respiratory distress syndrome (ARDS), disseminated intravascular coagulopathy (DIC), acute renal failure; plasma conc. 3.05 mg/L

Walubo; Seger; Human and Experimental Toxicology; vol. 18; nb. 2; (1999); p. 119 - 125, View in Reaxys

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340 of 373 Effect (Pharmacological Data)

enzyme; examination of

Species or Test-System (Pharmacological Data)

rat whole-brain spheroids

Concentration (Pharmacological Data)

50 - 500 μmol/l

Kind of Dosing (Pharmacological Data)

solut. of title comp. in EtOH was added into culture medium; conc. EtOH 1 percent v/v; culture was re-treated on the 3rd day of exposure

Method (Pharmacological Data)

in vitro; 12-day-old rat brain spheroids, 3.5E7 cells per flask; exposure to title comp. for 5 days; intracellular levels of glutathione (GSH) were measured by fluorometric method

Further Details (Pharmacological Data)

rat whole-brain spheroids from 16-day-old fetuses; in DMEM supplem. with 10 percent FCS; at 37 deg C and 9 percent CO2; control: EtOH only

Comment (Pharmacological Data)

No effect

Metabolite XRN (Pharmacological Data)

3251333; 8411436

Metabolite (Pharmacological Data)

(+/-)-DHMA; 6-hydroxymethylenedioxymethamphetamine

Walker; Davenport-Jones; Fox; Atterwill; Cell Biology and Toxicology; vol. 15; nb. 3; (1999); p. 137 - 142, View in Reaxys 341 of 373 Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

rat whole-brain spheroids

Concentration (Pharmacological Data)

50 - 500 μmol/l

Kind of Dosing (Pharmacological Data)

solut. of title comp. in EtOH was added into culture medium; conc. EtOH 1 percent v/v; culture was re-treated on the 3rd day of exposure

Method (Pharmacological Data)

in vitro; 12-day-old rat brain spheroids, 3.5E7 cells per flask; exposure to title comp. for 5 days; neurotoxicity markers glial fibrillary acidic protein (GFAP) and serotonin (5-HT) were determined by an ELISA assay and by fluorometric method, respect.

Further Details (Pharmacological Data)

rat whole-brain spheroids from 16-day-old fetuses; in DMEM supplem. with 10 percent FCS; at 37 deg C and 9 percent CO2; control: EtOH only

Comment (Pharmacological Data)

No effect

Metabolite XRN (Pharmacological Data)

3251333; 8411436

Metabolite (Pharmacological Data)

(+/-)-DHMA; 6-hydroxymethylenedioxymethamphetamine

Walker; Davenport-Jones; Fox; Atterwill; Cell Biology and Toxicology; vol. 15; nb. 3; (1999); p. 137 - 142, View in Reaxys 342 of 373 Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Dark Agouti rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

15 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. in saline; saline as control

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Method (Pharmacological Data)

rats 150-180 g weight; housed at 21 deg C, 12 h L:D; degeneration of 5-HT neurones in brain was judged by 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), dopamine, dihydroxyphenylacetic acid (DOPAC) conc. in brain and (3H)-paroxetine binding in cortex

Further Details (Pharmacological Data)

5-HT, 5-HIAA were measured in cortex, hippocampus and striatum, dopamine and DOPAC were measured in striatum 7 days posttreatment by HPLC; (3H)-paroxetine binding was measured by scintillation spectrometry

Results

decrease in 5-HT and 5-HIAA conc. in cortex, hippocampus and striatum; no effect on dopamine and DOPAC content in striatum; decrease in (3H)-paroxetine binding in cortex (plot)

Colado, Maria Isabel; Granados, Raquel; O'Shea, Esther; Esteban, Blanca; Green, A. Richard; Pharmacology and Toxicology; vol. 84; nb. 6; (1999); p. 261 - 266, View in Reaxys 343 of 373 Effect (Pharmacological Data)

body temperature; effect on

Species or Test-System (Pharmacological Data)

Dark Agouti rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

15 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. in saline; saline as control

Method (Pharmacological Data)

rats 150-180 g weight; housed at 21 deg C, 12 h L:D; rectum temperature was measured with thermocouple probe

Results

0.2-1.6 deg C dose-dependent increase in rectal temperature lasting for 5 h posttreatment; peak effect by 30 min after injection (plot)

Colado, Maria Isabel; Granados, Raquel; O'Shea, Esther; Esteban, Blanca; Green, A. Richard; Pharmacology and Toxicology; vol. 84; nb. 6; (1999); p. 261 - 266, View in Reaxys 344 of 373 Effect (Pharmacological Data)

hypertensive

Species or Test-System (Pharmacological Data)

human

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

75 - 125 mg

Kind of Dosing (Pharmacological Data)

title comp. given in soft-gelatine capsules

Method (Pharmacological Data)

systolic and diastolic blood pressure and heart rate were recorded at 15-90 min and at 2-24 h after administration of title comp.

Further Details (Pharmacological Data)

placebo control; reference comp.: amphetamine

Results

title comp. increased blood pressure with maximum at 90 min and heart rate with maximum at 60 min; reference comp. had similar effect in blood pressure, but delayed response in heart rate; fig., table

Mas, Marta; Farre, Magi; De la Torre, Rafael; Roset, Pere N.; Ortuno, Jordi; Segura, Jordi; Cami, Jordi; Journal of Pharmacology and Experimental Therapeutics; vol. 290; nb. 1; (1999); p. 136 - 145, View in Reaxys 345 of 373 Effect (Pharmacological Data)

thermoregulatory

Species or Test-System (Pharmacological Data)

human

Sex

male

Route of Application

peroral

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Concentration (Pharmacological Data)

75 - 125 mg

Kind of Dosing (Pharmacological Data)

title comp. given in soft-gelatine capsules

Method (Pharmacological Data)

oral temperature was recorded at 15-90 min and at 2-24 h after administration of title comp.

Further Details (Pharmacological Data)

placebo control

Comment (Pharmacological Data)

No effect

mydriatic

Species or Test-System (Pharmacological Data)

human

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

75 - 125 mg

Kind of Dosing (Pharmacological Data)

title comp. given in soft-gelatine capsules

Method (Pharmacological Data)

pupillary diameter was recorded with Haab pupil at 30-60 min and at 2-24 h after administration of title comp.; ECG was continuously monitored

Further Details (Pharmacological Data)

placebo control; reference comp.: amphetamine

Results

title comp. increased pupillary diameter with maximum at 1-2 h; reference comp. had similar effect at 10 h; table

releasing hormones

Species or Test-System (Pharmacological Data)

human

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

75 - 125 mg

Kind of Dosing (Pharmacological Data)

title comp. given in soft-gelatine capsules

Method (Pharmacological Data)

blood samples were obtained at 15-90 min and at 2-24 h after administration of title comp.; plasma concentration of cortisol was determined by fluorescence polarization immunoassay

Further Details (Pharmacological Data)

placebo control; reference comp.: amphetamine

Results

title comp. increased cortisol concentration with maximum at 2 h; reference comp. had no effect; fig., table

releasing hormones

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Species or Test-System (Pharmacological Data)

human

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

75 - 125 mg

Kind of Dosing (Pharmacological Data)

title comp. given in soft-gelatine capsules

Method (Pharmacological Data)

blood samples were obtained at 15-90 min and at 2-24 h after administration of title comp.; plasma concentration of growth hormone was determined by solid-phase, two-site chemiluminescent enzyme immunometric

Further Details (Pharmacological Data)

placebo control

Comment (Pharmacological Data)

No effect

pharmacokinetics

Species or Test-System (Pharmacological Data)

human

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

75 - 125 mg

Kind of Dosing (Pharmacological Data)

title comp. given in soft-gelatine capsules

Method (Pharmacological Data)

plasma concentration of title comp. was determined at 15-90 min and at 2-24 h after nadministration of title comp.; pharmacokinetic parameters were calculated

Further Details (Pharmacological Data)

T1/2a: absorption half-life; T1/2 elimination half-life

Results

Cmax 130.9-236 ng/ml; Tmax 1.8-2.4 h; AUC0-24 1331.5-2623.7 ng/ml/h; AUCtotal 1541.6-3190.7; T1/2a 0.42-0.42 h; T1/2 7.86-8.73 h; table

releasing hormones

Species or Test-System (Pharmacological Data)

human

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

75 - 125 mg

Kind of Dosing (Pharmacological Data)

title comp. given in soft-gelatine capsules

Method (Pharmacological Data)

blood samples were obtained at 15-90 min and at 2-24 h after administration of title comp.; plasma concentration of prolactin was determined by microparticle enzyme immunoassay

Further Details (Pharmacological Data)

placebo control; reference comp.: amphetamine

Results

title comp. at 125 mg increased prolactin concentration with maximum at 2 h; reference comp. had no effect; fig., table

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neurochemical, acute

Species or Test-System (Pharmacological Data)

CBA mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

50 mg/kg

Kind of Dosing (Pharmacological Data)

single dose; vehicle: saline

Exposure Period (Pharmacological Data)

Method (Pharmacological Data)

body weight 20-25 g; food and water ad libitum; administration of drug; killed at 1, 3 or 6 h after administration; samples of striatum (S), cortex (C) and hippocampus (H) removed

Further Details (Pharmacological Data)

tissue levels of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine, and 3,4-dihydroxyphenylacetic acid (DOPAC); HPLC analysis

Results

5-HT: signific. decrease in all tissues, return to normal in H and S at 6 h; 5-HIAA: reduction at 1 and 3 h, return to control except remained low in C at 6 h; dopamine in S: decrease at 1 h, then increase; DOPAC in S: decrease at first, increase later

Zheng, Yiwen; Russell, Bruce; Schmierer, David; Laverty, Richard; Journal of Pharmacy and Pharmacology; vol. 49; nb. 1; (1997); p. 89 - 96, View in Reaxys 352 of 373 Effect (Pharmacological Data)

neurochemical, long-term

Species or Test-System (Pharmacological Data)

CBA mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

25 mg/kg

Kind of Dosing (Pharmacological Data)

doses repeted 3 times in 24 h period (usually 17:00, 09:00, 17:00); vehicle: saline

Exposure Period (Pharmacological Data)

Method (Pharmacological Data)

body weight 20-25 g; food and water ad libitum; administration of drug; killed 7 d after last dose; samples of striatum removed

Further Details (Pharmacological Data)

striatal levels of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC); HPLC analysis

Results

levels ( percent of control) of: DOPAC 70.8 (P<0.01), dopamine 79.7 (P<0.01), 5-HIAA 78.6 (P<0.05), and 5-HT 77.2 (P<0.05)

Zheng, Yiwen; Russell, Bruce; Schmierer, David; Laverty, Richard; Journal of Pharmacy and Pharmacology; vol. 49; nb. 1; (1997); p. 89 - 96, View in Reaxys 353 of 373 Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

Dark Agouti rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 - 100 mg/kg

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Kind of Dosing (Pharmacological Data)

as hydrochloride

Exposure Period (Pharmacological Data)

0.08 - 24 h

Method (Pharmacological Data)

back hair of 6-week-old rats shaved 5 d before title comp. administration; hair root plucked out from shaved area at determined times after drug administration; monitoring of survival; determination of drug and its metabolite levels in hair roots; GC/MS

Results

lethal toxicity of title comp. developed dose-dependently; metabolized to methylenedioxyamphetamine (MDA); time courses of title comp. incorporation and MDA/drug ratios before and after death

Nakahara, Yuji; Kikura, Ruri; Biological and Pharmaceutical Bulletin; vol. 20; nb. 9; (1997); p. 969 - 972, View in Reaxys 354 of 373 Effect (Pharmacological Data)

toxicity

Endpoint of Effect (Pharmacological Data)

mortality

Species or Test-System (Pharmacological Data)

albino Sprague-Dawley rat

Sex

female

Route of Application

peroral

Concentration (Pharmacological Data)

20 - 320 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in distilled water

Method (Pharmacological Data)

title comp. admin. to rats and lethality determined

Results

several deaths occurred within 4 h of title comp. admin. in 40, 80 , 160, and 320 mg/kg groups

De Souza; Kelly; Harkin; Leonard; Pharmacology and Toxicology; vol. 80; nb. 5; (1997); p. 207 - 210, View in Reaxys 355 of 373 Effect (Pharmacological Data)

toxicity

Species or Test-System (Pharmacological Data)

albino Sprague-Dawley rat

Sex

female

Route of Application

peroral

Concentration (Pharmacological Data)

20 - 80 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in distilled water

Method (Pharmacological Data)

rats treated with title comp.; body weight (BW), food and water intake determined before and 24 h after administration; rectal temperature measured before and 24 h post dosing; haematological determination at 24 h post dosing

Further Details (Pharmacological Data)

haematological parameters (erythrocyte haemoglobin, haemtocrit and leucocytes) were measured

Results

BW, food and water intake were signif. reduced at 20 and 40 mg/kg; significant dose-related hyperthermic responses up to 8 h post dosing (diagram); non-significant dose-related increase in haemoglobin conc.

De Souza; Kelly; Harkin; Leonard; Pharmacology and Toxicology; vol. 80; nb. 5; (1997); p. 207 - 210, View in Reaxys 356 of 373 Effect (Pharmacological Data)

behavioural symptoms

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Species or Test-System (Pharmacological Data)

albino Sprague-Dawley rat

Sex

female

Route of Application

peroral

Concentration (Pharmacological Data)

20 - 80 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in distilled water

Method (Pharmacological Data)

title comp. administered to rats; locomotor activity in home cage recorded continuosly by infrared device during a 24 h period following admin. of title comp.

Results

title comp. showed significant increase in activity at 20 mg/kg and 40 mg/kg up to 9 and 10 h post dosing, resp.; no significant difference in activity observed in 80 mg/kg (diagram)

De Souza; Kelly; Harkin; Leonard; Pharmacology and Toxicology; vol. 80; nb. 5; (1997); p. 207 - 210, View in Reaxys 357 of 373 Effect (Pharmacological Data)

incorporation into hair

Species or Test-System (Pharmacological Data)

Dark-Agouti rats

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 mg/kg

Exposure Period (Pharmacological Data)

10 d

Method (Pharmacological Data)

rats of 95-105 g, 5 wks old; back hair of rats shaved; hair collected; blood collected 5, 15, 30, 60, 120, 360 min after dosing; plasma prepared; areas under conc. vs. time curve (AUCs) calculated; incorporated rates (ICRs) determination

Results

AUC, 121.2 μg*min/ml; 93.40 ng/mg conc. in hair; ICR, 0.77

Nakahara, Yuji; Kikura, Ruri; Archives of Toxicology; vol. 70; nb. 12; (1996); p. 841 - 849, View in Reaxys 358 of 373 Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 - 40 mg/kg

Kind of Dosing (Pharmacological Data)

as hydrochloride; single dose

Method (Pharmacological Data)

in vivo; rats weighed 200-250 g; 12 h light/dark cycle; kept at 23-25 deg C; food and water ad libitum; rats killed 0.5-6 h after treatment; blood samples collected; brains removed and homogenized

Further Details (Pharmacological Data)

title comp. and MDA levels measured by GC-MS; MDA: 3,4-methylenedioxyamphetamine

Results

title comp. conc. in brain was dose-dependent and peaked within the first 2 h and then dropped to 10-20 percent of highest conc. at 6 h in brain and plasma; conc. of (-)enantiomer was higher then (+)enantiomer; MDA was major metabolite in brain

Metabolite XRN (Pharmacological Data)

150196

Metabolite (Pharmacological Data)

3,4-methylenedioxyamphetamine

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Chu, Teresa; Kumagai, Yoshito; DiStefano, Emma W.; Cho, Arthur K.; Biochemical Pharmacology; vol. 51; nb. 6; (1996); p. 789 - 796, View in Reaxys 359 of 373 Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Method (Pharmacological Data)

rats (180-200 g) received twice-daily injections of title comp. or saline for 4 days; on day 14-16-microdialysis experiment collecting samples every 20 min of perfusion of hippocampus or frontal cortex; levels of 5-HT and 5-HIAA assayed

Further Details (Pharmacological Data)

5-HT: 5-hydroxytryptamine; 5-HIAA: 5-hydroxyindoleacetic acid

Results

basal 5-HT levels in frontal cortex and hippocampus were not altered by title comp.; basal 5-HIAA levels in frontal cortex and hippocampus were reduced by 52 percent and 45 percent respectively (diagram)

Gartside; McQuade; Sharp; Journal of Pharmacology and Experimental Therapeutics; vol. 279; nb. 1; (1996); p. 277 - 283, View in Reaxys 360 of 373 Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Method (Pharmacological Data)

rats (180-200 g) received twice-daily injections of title comp. or saline for 4 days; 2-3 h later 20-min electrical stimulation of DRN and 60 min later of MRN (for hippocampus only); levels of 5-HT and 5-HIAA assayed

Further Details (Pharmacological Data)

5-HT: 5-hydroxytryptamine; 5-HIAA: 5-hydroxyindoleacetic acid; DRN: dorsal raphe nucleus; MRN: median raphe nucleus; on day 14-16 - microdialysis collecting samples every 20 min of perfusion of hippocampus or frontal cortex

Results

in frontal cortex title comp. reduced the increase of 5-HT levels, caused by DRN stimulation; in hippocampus title comp. did not after 5-HT levels in both DRN and MRN-stimulated rats (diagram)

Gartside; McQuade; Sharp; Journal of Pharmacology and Experimental Therapeutics; vol. 279; nb. 1; (1996); p. 277 - 283, View in Reaxys 361 of 373 Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Method (Pharmacological Data)

rats (180-200 g) received twice-daily injections of title comp. or saline for 4 days; on day 14-16 extracellular recordings from DRN; classical 5-HT and burst-firing neurons were recorded

Further Details (Pharmacological Data)

5-HT: 5-hydroxytryptamine; DRN: dorsal raphe nucleus

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Results

title comp. did not alter the number of classical 5-HT and burst-firing neurons in comparison to control; mean firing rate and regularity of firing was also unchanged (table)

Gartside; McQuade; Sharp; Journal of Pharmacology and Experimental Therapeutics; vol. 279; nb. 1; (1996); p. 277 - 283, View in Reaxys 362 of 373 Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Dark Agouty rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

10 mg/kg

Method (Pharmacological Data)

160-180 g rats treated with title comp., then rectal temp. measured for 24 h; 7 d after title comp., rats killed by decapitation, brain removed, cortex and hippocampus dissected

Further Details (Pharmacological Data)

5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) measured by HPLC; <3H>paroxetine binding in cortex assayed by described method (Hewitt and Green, Neuropharmacology 33, 1589)

Results

significant hyperthermia in 0-2 h; 40 percent loss of 5-HT and 5-HIAA; 30 percent loss in <3H>paroxetin binding

Colado, Maria Isabel; Green, A. Richard; European Journal of Pharmacology; vol. 280; nb. 3; (1995); p. 343 - 346, View in Reaxys 363 of 373 Effect (Pharmacological Data)

Accumulation

Species or Test-System (Pharmacological Data)

human

Sex

male

Method (Pharmacological Data)

chronic drug abuse; sampling head hair and fingernail; hot alkaline hydrolysis; deuterated internal standard; three-step extraction procedure; derivatization by propionylation; GC/MS analysis

Further Details (Pharmacological Data)

22-year old male

Results

concentration: 53.4 ng/mg in hair and 60.2 ng/mg in fingernail

Cirimele; Kintz; Mangin; Archives of Toxicology; vol. 70; nb. 1; (1995); p. 68 - 69, View in Reaxys 364 of 373 Effect (Pharmacological Data)

AUC

Species or Test-System (Pharmacological Data)

dark-agouti rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 mg/kg

Kind of Dosing (Pharmacological Data)

drug administered once a day for 10 successive days

Exposure Period (Pharmacological Data)

10 d

Method (Pharmacological Data)

rats 5 weeks old; back hair shaved before experiment; blood samples collected 5, 15, 30, 60, 120, 360 min after drug administration; newly grown hair samples collected 4 weeks after first drug administration

Further Details (Pharmacological Data)

drug level in plasma and hair determination; GC/MS; HPLC

Type (Pharmacological Data)

AUC

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Value of Type (Pharmacological Data)

6.4 μg*min/ml

Results

concentration in hair <H> = 3.85 ng/mg; drug incorporation rate ICR (<H>/AUC) = 0.6

Nakahara; Takahashi; Kikura; Biological and Pharmaceutical Bulletin; vol. 18; nb. 9; (1995); p. 1223 - 1227, View in Reaxys 365 of 373 Effect (Pharmacological Data)

drug interaction

Species or Test-System (Pharmacological Data)

rat

Concentration (Pharmacological Data)

20 mg/kg

Method (Pharmacological Data)

rats treated with title compound; 0.01-1.0 mg/kg MDL 100,907 given s.c. 30 min prior to title compound and 90 min prior to sacrifie; dopamine efflux in medial prefrontal cortex determined

Further Details (Pharmacological Data)

MDL 100,907:R-(+)-α-(2,3-dimethoxyphenyl)-1-<2-(4-fluorophenylethyl)>-4-piperidinemethanol

Results

selective blockade of title compound-induced increase in striatal dopamine synthesis by MDL 100,907

Schmidt; Sorensen; Kehne; Carr; Palfreyman; Life Sciences; vol. 56; nb. 25; (1995); p. 2209 - 2222, View in Reaxys 366 of 373 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

C57BL/6J mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

10 - 120 mg/kg

Kind of Dosing (Pharmacological Data)

as hydrochloride

Method (Pharmacological Data)

in vivo; 21-to 32-g mice housed in groups of 4 in dimly illuminated and quiet testing room with free access to food and water; gnawing upon corrugated packing paper was behavioral measure (8 mice per dose, 75 min after drug administration)

Results

did not increase gnawing; lethal effects were observed in at least one of eight mice, always preceded by convulsive episodes at 120 mg/kg

Tirelli; Witkin; Journal of Pharmacology and Experimental Therapeutics; vol. 273; nb. 1; (1995); p. 7 - 16, View in Reaxys 367 of 373 Effect (Pharmacological Data)

potassium channel blockade

Species or Test-System (Pharmacological Data)

rat hippocampal neurons

Concentration (Pharmacological Data)

0.1 - 500 μmol/l

Method (Pharmacological Data)

in vitro; patch-clamp technique

Results

reduced conductance of a 50-pS barium-sensitive resting K+ channel and increased neuronal exitability

Premkumar; Ahern; Journal of Pharmacology and Experimental Therapeutics; vol. 274; nb. 2; (1995); p. 718 - 722, View in Reaxys 368 of 373 Effect (Pharmacological Data) Species or Test-System (Pharmacological Data)

modulation of synaptic transmission rat hippocampal neurons

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Concentration (Pharmacological Data)

50 - 200 μmol/l

Method (Pharmacological Data)

in vitro; patch-clamp technique

Further Details (Pharmacological Data)

EPSCs, excitatory postsynaptic currents; IPSCs, inhibitory postsynaptic currents; EACs, excitatory autaptic currents; IACs, inhibitory autaptic currents

Results

enhanced synaptic strength by irreversibly increasing the amplitude of EACs and the frequency of spontaneous EPSCs; no alteration of the amplitude of IACs or the frequency of spontaneous IPSCs; reversibly prolonged decay phase of IACs and spont. IPSCs

Premkumar; Ahern; Journal of Pharmacology and Experimental Therapeutics; vol. 274; nb. 2; (1995); p. 718 - 722, View in Reaxys 369 of 373 Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

40 mg/kg

Kind of Dosing (Pharmacological Data)

as HCl salt

Method (Pharmacological Data)

in vivo; adult rats (175-199 g) individually housed under standard environmental conditions (14 h/10 h light/dark cycle, 24 deg C) with ad libitum access to food and water; killed by decapitation at 0.125-7 d after title comp. administration

Further Details (Pharmacological Data)

striatum, hippocampus and frontal cortex were dissected; 5-HT uptake carrier measurements, 5-HT, 5-HIAA and 5-HTP determinations, and malondialdehyde assay were carried out in tissue samples

Results

induced significant decrease in both <3H>paroxetine binding Bmax and 5-HT and 5-HIAA levels 7 d after treatment; max. increased formation of thiobarbituric acid reactive substances 12 h after treatment; significantly reduced TPH activity after 18 h

Sprague; Nichols; Journal of Pharmacology and Experimental Therapeutics; vol. 273; nb. 2; (1995); p. 667 - 673, View in Reaxys 370 of 373 Comment (Pharmacological Data)

effects on chronotropic responses in female rat isolated atria, effects on female rat isolated perfused heart (produced dishrytmias), effects on rabbit isolated perfused and superfused ear artery

Fitzgerald; Reid; Journal of Pharmacy and Pharmacology; vol. 46; nb. 10; (1994); p. 826 - 832, View in Reaxys 371 of 373 Comment (Pharmacological Data)

drug substitution: ED50 = 2.79 μmol/kg

Johnson; Frescas; Oberlender; Nichols; Journal of Medicinal Chemistry; vol. 34; nb. 5; (1991); p. 1662 - 1668, View in Reaxys 372 of 373 Comment (Pharmacological Data)

analgetic potency, influence on motor activity (male NMRI-mouse, doses: 100 mg/kg, 20 mg/kg, 10 mg/kg, p.o.); phychotomimetic potency (man and woman, dose 100-160 mg, p.o.)

Braun; Shulgin; Arzneimittel-Forschung; vol. 30; nb. 5; (1980); p. 825 - 830, View in Reaxys 373 of 373 Comment (Pharmacological Data)

central analgesia activity (mice); central stimulation activity: motor activity (mice), psychotomimetic activity (human)

Braun; Shulgin; Journal of Pharmaceutical Sciences; vol. 69; nb. 2; (1980); p. 192 - 195, View in Reaxys Exposure Assessment (2) Exposure Sources presence in surface water; Llobregat River, its main tributaries (Cardener River and Anoia River)

human source contaminants

References Huerta-Fontela, Maria; Galceran, Maria Teresa; Ventura, Francesc; Environmental Science and Technology; vol. 42; nb. 18; (2008); p. 6809 - 6816, View in Reaxys

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and Rubi creek in NE Spain; sampling in January, March and May 2007 presence in hair and fingernails; 22-year-old male

chronic drug abuse

Cirimele; Kintz; Mangin; Archives of Toxicology; vol. 70; nb. 1; (1995); p. 68 - 69, View in Reaxys

Concentration in the Environment (18) 1 of 18

Media (Concentration in the Environment)

sewage water

Location

Gandia, Spain

Contamination Concentration

47.4 ng/l

Method, Remarks (Concentration in the Environment)

samples collected from STP of tourist cites of Gandia; influent 24-h composite samples collected on 26th of July 2007; solid-phase extraction-liquid chromatography-electrospraytandem mass spectrometry

Postigo, Cristina; Lopez De Alda, Maria J.; Barcelo, Damia; Analytical Chemistry; vol. 80; nb. 9; (2008); p. 3123 3134, View in Reaxys 2 of 18

Media (Concentration in the Environment)

sewage water

Location

Gandia, Spain

Contamination Concentration

30.3 ng/l

Method, Remarks (Concentration in the Environment)

samples collected from STP of tourist cites of Gandia; effluent 24-h composite samples collected on 26th of July 2007; solid-phase extraction-liquid chromatography-electrospraytandem mass spectrometry

Postigo, Cristina; Lopez De Alda, Maria J.; Barcelo, Damia; Analytical Chemistry; vol. 80; nb. 9; (2008); p. 3123 3134, View in Reaxys 3 of 18

Media (Concentration in the Environment)

sewage water

Location

Benicassim, Spain

Contamination Concentration

245.0 ng/l

Method, Remarks (Concentration in the Environment)

samples collected from STP of tourist cites of Benicassim; influent 24-h composite samples collected on 26th of July 2007; solid-phase extraction-liquid chromatography-electrospray-tandem mass spectrometry

Postigo, Cristina; Lopez De Alda, Maria J.; Barcelo, Damia; Analytical Chemistry; vol. 80; nb. 9; (2008); p. 3123 3134, View in Reaxys 4 of 18

Media (Concentration in the Environment)

sewage water

Location

Barcelona, Spain

Contamination Concentration

133.6 ng/l

Method, Remarks (Concentration in the Environment)

samples collected from major STP of Barcelona; influent 24-h composite samples collected every day during first week of July 2007; solid-phase extraction-liquid chromatography-electrospray-tandem mass spectrometry

Postigo, Cristina; Lopez De Alda, Maria J.; Barcelo, Damia; Analytical Chemistry; vol. 80; nb. 9; (2008); p. 3123 3134, View in Reaxys 5 of 18

Media (Concentration in the Environment)

sewage water

Location

Barcelona, Spain

Contamination Concentration

82.1 ng/l

133/242

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Method, Remarks (Concentration in the Environment)

samples collected from major STP of Barcelona; effluent 24-h composite samples collected every day during first week of July 2007; solid-phase extraction-liquid chromatography-electrospray-tandem mass spectrometry

Postigo, Cristina; Lopez De Alda, Maria J.; Barcelo, Damia; Analytical Chemistry; vol. 80; nb. 9; (2008); p. 3123 3134, View in Reaxys 6 of 18

Media (Concentration in the Environment)

sewage water

Location

Valencia, Spain

Contamination Concentration

38.2 ng/l

Method, Remarks (Concentration in the Environment)

samples collected from STP of tourist cites of Valencia; effluent 24-h composite samples collected on 26th of July 2007; solid-phase extraction-liquid chromatography-electrospraytandem mass spectrometry

Postigo, Cristina; Lopez De Alda, Maria J.; Barcelo, Damia; Analytical Chemistry; vol. 80; nb. 9; (2008); p. 3123 3134, View in Reaxys 7 of 18

Media (Concentration in the Environment)

sewage water

Location

Valencia, Spain

Contamination Concentration

113.0 ng/l

Method, Remarks (Concentration in the Environment)

samples collected from STP of tourist cites of Valencia; influent 24-h composite samples collected on 26th of July 2007; solid-phase extraction-liquid chromatography-electrospraytandem mass spectrometry

Postigo, Cristina; Lopez De Alda, Maria J.; Barcelo, Damia; Analytical Chemistry; vol. 80; nb. 9; (2008); p. 3123 3134, View in Reaxys 8 of 18

Media (Concentration in the Environment)

sewage water

Location

Benicassim, Spain

Contamination Concentration

376 ng/l

Method, Remarks (Concentration in the Environment)

samples collected from STP of tourist cites of Benicassim; effluent 24-h composite samples collected on 26th of July 2007; solid-phase extraction-liquid chromatography-electrospray-tandem mass spectrometry

Postigo, Cristina; Lopez De Alda, Maria J.; Barcelo, Damia; Analytical Chemistry; vol. 80; nb. 9; (2008); p. 3123 3134, View in Reaxys 9 of 18

Media (Concentration in the Environment)

water

Location

Llobregat River basin, NE Spain

Contamination Concentration

2 - 10 ng/l

Method, Remarks (Concentration in the Environment)

granulated activated carbon filtration samples of treated water collected in a drinking water treatment plant during January to June 2007; analyzed by ultraperformance LCESI/MS/MS in selected reaction monitoring mode

Huerta-Fontela, Maria; Galceran, Maria Teresa; Ventura, Francesc; Environmental Science and Technology; vol. 42; nb. 18; (2008); p. 6809 - 6816, View in Reaxys 10 of 18

Media (Concentration in the Environment)

water

Location

Llobregat River basin, NE Spain

Contamination Concentration

4 - 120 ng/l

Method, Remarks (Concentration in the Environment)

ozonated samples of treated water collected in a drinking water treatment plant during January to June 2007; analyzed by ultraperformance LC-ESI/MS/MS in selected reaction monitoring mode

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Huerta-Fontela, Maria; Galceran, Maria Teresa; Ventura, Francesc; Environmental Science and Technology; vol. 42; nb. 18; (2008); p. 6809 - 6816, View in Reaxys 11 of 18

Media (Concentration in the Environment)

water

Location

Llobregat River basin, NE Spain

Contamination Concentration

5 - 135 ng/l

Method, Remarks (Concentration in the Environment)

raw water samples treated by prechlorination, coagulation/flocculation and sand filtration collected in a drinking water treatment plant during January to June 2007; analyzed by ultraperformance LC-ESI/MS/MS in selected reaction monitoring mode

Huerta-Fontela, Maria; Galceran, Maria Teresa; Ventura, Francesc; Environmental Science and Technology; vol. 42; nb. 18; (2008); p. 6809 - 6816, View in Reaxys 12 of 18

Media (Concentration in the Environment)

surface water

Location

Llobregat River, NE Spain

Contamination Concentration

4 - 190 ng/l

Method, Remarks (Concentration in the Environment)

samples collected during January to June 2007; analyzed by ultraperformance LCESI/MS/MS in selected reaction monitoring mode

Huerta-Fontela, Maria; Galceran, Maria Teresa; Ventura, Francesc; Environmental Science and Technology; vol. 42; nb. 18; (2008); p. 6809 - 6816, View in Reaxys 13 of 18

Media (Concentration in the Environment)

surface water

Location

Llobregat River, NE Spain

Contamination Concentration

1 - 40 ng/l

Method, Remarks (Concentration in the Environment)

mean conc.; samples collected once a week every Monday and at the same time (10:00 am) during March 2006 to May 2007 at the intake of a drinking water treatment plant; analyzed by ultraperformance LC-ECI/MS/MS in selected reaction monitoring mode; fig.

Huerta-Fontela, Maria; Galceran, Maria Teresa; Ventura, Francesc; Environmental Science and Technology; vol. 42; nb. 18; (2008); p. 6809 - 6816, View in Reaxys 14 of 18

Media (Concentration in the Environment)

surface water

Location

Llobregat River basin, NE Spain

Contamination Concentration

0 - 55 ng/l

Method, Remarks (Concentration in the Environment)

mean conc.; samples collected over 7 consecutive days at the same time (10:00 am) during December 2006 at the intake of a drinking water treatment plant; analyzed by ultraperformance LC-ESI/MS/MS in selected reaction monitoring mode

Huerta-Fontela, Maria; Galceran, Maria Teresa; Ventura, Francesc; Environmental Science and Technology; vol. 42; nb. 18; (2008); p. 6809 - 6816, View in Reaxys 15 of 18

Media (Concentration in the Environment)

wastewater

Location

Nosedo (Milan), Italy

Contamination Concentration

4.4 - 14.2 ng/l

Method, Remarks (Concentration in the Environment)

8 water sample collected during 1 week in February 2006 from wastewater treatment plant influents and effluents; HPLC-MS-MS analyzed

Castiglioni, Sara; Zuccato, Ettore; Crisci, Elisabetta; Chiabrando, Chiara; Fanelli, Roberte; Bagnati, Renzo; Analytical Chemistry; vol. 78; nb. 24; (2006); p. 8421 - 8429, View in Reaxys

135/242

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16 of 18

Media (Concentration in the Environment)

wastewater

Location

Lugano, Switzerland

Contamination Concentration

5.1 - 13.6 ng/l

Method, Remarks (Concentration in the Environment)

8 water sample collected during 1 week in March 2006 from wastewater treatment plant influents and effluents; HPLC-MS-MS analyzed

Castiglioni, Sara; Zuccato, Ettore; Crisci, Elisabetta; Chiabrando, Chiara; Fanelli, Roberte; Bagnati, Renzo; Analytical Chemistry; vol. 78; nb. 24; (2006); p. 8421 - 8429, View in Reaxys 17 of 18

Species (Concentration in the Environment)

human

Location

Barcelona, Spain

Contamination Concentration

0 - 0.012 mg/kg

Method, Remarks (Concentration in the Environment)

in meconium; up to 600 samples, only 1 positive; mother who declared sporadic consumption of "amphetamines"; internal standard; methanol-HCl treatment; Bond Elut Certify solid-phase extraction column; HPLC-MS; in positive ESI mode; SIM acquisition

Pichini, Simona; Pacifici, Roberta; Pellegrini, Manuela; Marchei, Emilia; Lozano, Jaime; Murillo, Janeth; Vall, Oriol; Garcia-Algar, Oscar; Analytical Chemistry; vol. 76; nb. 7; (2004); p. 2124 - 2132, View in Reaxys 18 of 18

Media (Concentration in the Environment)

waste water effluents

Location

South Carolina

Contamination Concentration

0.5 ng/l

Method, Remarks (Concentration in the Environment)

Polar Organic Chemical Integrative Sampling and microliquid chromatography-electrospray/ion-trap mass spectrometry separation techniques; samples collected summer July 1 - 30, 2002

Jones-Lepp; Alvarez; Petty; Huckins; Archives of Environmental Contamination and Toxicology; vol. 47; nb. 4; (2004); p. 427 - 439, View in Reaxys Use (50) Laboratory Use and Handling

Use Pattern

Location

air sensitive

References Schulze, Matthias; Synthetic Communications; vol. 40; nb. 10; (2010); p. 1461 - 1476, View in Reaxys

neurotransmitter modulating agent

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

Neuronal cell damage

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

Death caused by transient cerebral hypoxia

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

Death caused by transient cerebral ischemia

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

transient cerebral hypoxia

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

Transient ischemic condition

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

Neuronal cell damage caused by transient cerebral hypoxia

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

Neuronal cell damage caused

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

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by transient cerebral ischemia cerebral hypoxic condition

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

Cerebral ischemic condition

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

transient cerebral hypoxic condition caused by loss of blood

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

transient cerebral hypoxic condition caused by a heart attack

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

transient cerebral hypoxic condition caused by strangulation

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

transient cerebral hypoxic condition caused by surgery

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

transient cerebral hypoxic condition caused by cardiac surgery

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

transient cerebral hypoxic condition caused by stroke

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

transient cerebral hypoxic condition caused by air-way blockage

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

transient cerebral hypoxic condition caused by ischemic optic neuropathy

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

transient cerebral hypoxic condition caused by spinal cord injuries

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

transient cerebral hypoxic condition caused by traumatic brain injury

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

transient cerebral hypoxic condition caused by low blood pressure

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

transient cerebral ischemic condition caused by loss of blood

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

transient cerebral ischemic condition caused by a heart attack

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

transient cerebral ischemic condi-

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

137/242

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tion caused by strangulation transient cerebral ischemic condition caused by surgery

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

transient cerebral ischemic condition caused by cardiac surgery

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

transient cerebral ischemic condition caused by a stroke

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

transient cerebral ischemic condition caused by air-way blockage

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

transient cerebral ischemic condition caused by ischemic optic neuropathy

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

transient cerebral ischemic condition caused by spinal cord injuries

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

transient cerebral ischemic condition caused by traumatic brain injury

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

transient cerebral ischemic condition caused by low blood pressure

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

Neuronal cell damage due to lack of oxygen reaching the neuronal cells

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

Neuronal cell damage due to lack of glucose reaching the neuronal cells

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

Ischemic condition

Patent; THE UNIVERSITY OF MONTANA; WO2008/24660; (2008); (A2) English, View in Reaxys

Psychomotor stimulant

Patent; ABBOTT GMBH and CO.KG; WO2006/40177; (2006); (A1) English, View in Reaxys

illicit/illegal drug

Patent; BAYLOR COLLEGE OF MEDICINE; US2006/18921; (2006); (A1) English, View in Reaxys

Psychomotor stimulant

Page/Page column 87-88

Patent; ABBOTT GMBH and CO. KG; WO2006/40180; (2006); (A1) English, View in Reaxys

5HT receptors inhibition

Patent; MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH; WO2005/107473; (2005); (A2) English, View in Reaxys

Irritable bowel syndrome

Patent; MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH; WO2005/107473; (2005); (A2) English, View in Reaxys

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Hypertrophic pyloric stenosis

Patent; MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH; WO2005/107473; (2005); (A2) English, View in Reaxys

Intestinal pseudoobstruction

Patent; MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH; WO2005/107473; (2005); (A2) English, View in Reaxys

gastroparesis

Patent; MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH; WO2005/107473; (2005); (A2) English, View in Reaxys

Diabetic gastroparesis

Patent; MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH; WO2005/107473; (2005); (A2) English, View in Reaxys

Diabetic gastroenteropathy

Patent; MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH; WO2005/107473; (2005); (A2) English, View in Reaxys

Constipation

Patent; MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH; WO2005/107473; (2005); (A2) English, View in Reaxys

Hirschsprung's disease

Patent; MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH; WO2005/107473; (2005); (A2) English, View in Reaxys

Functional dyspepsia

Patent; MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH; WO2005/107473; (2005); (A2) English, View in Reaxys

Digestive tract conditions

Patent; MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH; WO2005/107473; (2005); (A2) English, View in Reaxys

Reaxys ID 5261849 View in Reaxys

H N

3/52 CAS Registry Number: 66142-89-0 Chemical Name: (S)-3,4-methylenedioxymethamphetamine; (+)-3,4-Methylenedioxymethamphetamine; “Ecstasy”; “Molly”; (+)-MDMA; (S)-MDMA; S-MDMA Linear Structure Formula: C11H15NO2 Molecular Formula: C11H15NO2 Molecular Weight: 193.246 Type of Substance: heterocyclic InChI Key: SHXWCVYOXRDMCX-QMMMGPOBSA-N Note:

O O

Substance Label (8) Label References MDMA

Wall, Stephen C.; Gu, Howard; Rudnick, Gary; Molecular Pharmacology; vol. 47; nb. 3; (1995); p. 544 550, View in Reaxys; Aguirre, Norberto; Galbete, Jose L.; Lasheras, Berta; Rio, Joaquin Del; European Journal of Pharmacology; vol. 281; nb. 1; (1995); p. 101 - 106, View in Reaxys; Malberg, Jessica E.; Sabol, Karen E.; Seiden, Lewis S.; Journal of Pharmacology and Experimental Therapeutics; vol. 278; nb. 1; (1996); p. 258 - 267, View in Reaxys; Haapala, Markus; Pol, Jaroslav; Saarela, Ville; Arvola, Ville; Kotiaho, Tapio; Ketola, Raimo A.; Franssila, Sami; Kauppila, Tiina J.; Kostiainen, Risto; Analytical Chemistry; vol. 79; nb. 20; (2007); p. 7867 - 7872, View in Reaxys; Harvey, Eric L.; Baker, Lisa E.; Psychopharmacology; vol. 233; nb. 4; (2016); p. 673 - 680, View in Reaxys

(S)-10a; (S)MDMA

S-MDMA

(S)-MDMA

Pizarro, Nieves; De la Torre, Rafael; Farre, Magi; Segura, Jordi; Llebaria, Amadeu; Joglar, Jesus; Bioorganic and Medicinal Chemistry; vol. 10; nb. 4; (2002); p. 1085 - 1092, View in Reaxys

MDMA; (Merck12 6015)

Crespi, Daniela; Mennini, Tiziana; Gobbi, Marco; British Journal of Pharmacology; vol. 121; nb. 8; (1997); p. 1735 - 1743, View in Reaxys

(S)-7e

Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374, View in Reaxys

S-2a: free base

Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015, View in Reaxys

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(S)-(+)-2

Nichols, David E.; Lloyd, David H.; Hoffman, Andrew J.; Nichols, Maxine B.; Yim, George K. W.; Journal of Medicinal Chemistry; vol. 25; nb. 5; (1982); p. 530 - 535, View in Reaxys

Derivative (2) Derivative

References

MDMA hydrochloride

Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374, View in Reaxys

MDMA hydrochloride

Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015, View in Reaxys

Optical Rotatory Power (1) 1 of 1

Type (Optical Rotatory Power)

[alpha]

Concentration (Optical Rotatory Power)

0.6 g/100ml

Solvent (Optical Rotatory Power)

water

Optical Rotatory Power [deg]

14.2

Wavelength (Optical Ro- 589 tatory Power) [nm] Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46, View in Reaxys NMR Spectroscopy (1) 1 of 1

Description (NMR Spec- Chemical shifts troscopy) Nucleus (NMR Spectroscopy)

Solvents (NMR Spectro- CDCl3 scopy) Frequency (NMR Spectroscopy) [MHz]

200

Pizarro, Nieves; De la Torre, Rafael; Farre, Magi; Segura, Jordi; Llebaria, Amadeu; Joglar, Jesus; Bioorganic and Medicinal Chemistry; vol. 10; nb. 4; (2002); p. 1085 - 1092, View in Reaxys Mass Spectrometry (2) Description (Mass References Spectrometry) GCMS (Gas chro- Schwaninger, Andrea E.; Meyer, Markus R.; Huestis, Marilyn A.; Maurer, Hans H.; Journal of Mass Specmatography mass trometry; vol. 46; nb. 7; (2011); p. 603 - 614, View in Reaxys spectrometry); Negative chemical ionization; Spectrum spectrum

Haapala, Markus; Pol, Jaroslav; Saarela, Ville; Arvola, Ville; Kotiaho, Tapio; Ketola, Raimo A.; Franssila, Sami; Kauppila, Tiina J.; Kostiainen, Risto; Analytical Chemistry; vol. 79; nb. 20; (2007); p. 7867 7872, View in Reaxys

Pharmacological Data (38) 1 of 38

Comment (Pharmacological Data)

Bioactivities present

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Llebaria, Amadeu; Joglar, Jesus; Bioorganic and Medicinal Chemistry; vol. 10; nb. 4; (2002); p. 1085 - 1092, View in Reaxys; Crespi, Daniela; Mennini, Tiziana; Gobbi, Marco; British Journal of Pharmacology; vol. 121; nb. 8; (1997); p. 1735 - 1743, View in Reaxys; Setola, Vincent; Hufeisen, Sandra J.; Grande-Allen, K. Jane; Vesely, Ivan; Glennon, Richard A.; Blough, Bruce; Rothman, Richard B.; Roth, Bryan L.; Molecular Pharmacology; vol. 63; nb. 6; (2003); p. 1223 - 1229, View in Reaxys; Haji-Momenian, Shahriar; Rieger, Jayson M.; Macdonald, Timothy L.; Brown, Milton L.; Bioorganic and Medicinal Chemistry; vol. 11; nb. 24; (2003); p. 5545 - 5554, View in Reaxys; Keizers, Peter H. J.; De Graaf, Chris; De Kanter, Frans J. J.; Oostenbrink, Chris; Feenstra, K. Anton; Commandeur, Jan N. M.; Vermeulen, Nico P. E.; Journal of Medicinal Chemistry; vol. 48; nb. 19; (2005); p. 6117 - 6127, View in Reaxys; Montgomery; Buon; Eibauer; Guiry; Keenan; McBean; British Journal of Pharmacology; vol. 152; nb. 7; (2007); p. 1121 - 1130, View in Reaxys; Haapala, Markus; Pol, Jaroslav; Saarela, Ville; Arvola, Ville; Kotiaho, Tapio; Ketola, Raimo A.; Franssila, Sami; Kauppila, Tiina J.; Kostiainen, Risto; Analytical Chemistry; vol. 79; nb. 20; (2007); p. 7867 - 7872, View in Reaxys; Barak, Larry S.; Salahpour, Ali; Zhang, Xiaodong; Masri, Bernard; Sotnikova, Tatyana D.; Ramsey, Amy J.; Violin, Jonathan D.; Lefkowitz, Robert J.; Caron, Marc G.; Gainetdinov, Raul R.; Molecular Pharmacology; vol. 74; nb. 3; (2008); p. 585 - 594, View in Reaxys; Carroll, F. Ivy; Abraham, Philip; Gong, Paul K.; Pidaparthi, Ramakrishna R.; Blough, Bruce E.; Che, Yingni; Hampton, Amber; Gunnell, Melinda; Lay Jr., Jackson O.; Peterson, Eric C.; Owens, S. Michael; Journal of Medicinal Chemistry; vol. 52; nb. 22; (2009); p. 7301 - 7309, View in Reaxys; Biezonski, Dominik K.; Meyer, Jerrold S.; Journal of Neurochemistry; vol. 112; nb. 4; (2010); p. 951 - 962, View in Reaxys; Puerta, Elena; Hervias, Isabel; Goni-Allo, Beatriz; Zhang, Steven F; Jordan, Joaquin; Starkov, Anatoly A; Aguirre, Norberto; British Journal of Pharmacology; vol. 160; nb. 2; (2010); p. 233 - 245, View in Reaxys; Lewin, Anita H.; Miller, Gregory M.; Gilmour, Brian; Bioorganic and Medicinal Chemistry; vol. 19; nb. 23; (2011); p. 7044 - 7048, View in Reaxys; Schwaninger, Andrea E.; Meyer, Markus R.; Huestis, Marilyn A.; Maurer, Hans H.; Journal of Mass Spectrometry; vol. 46; nb. 7; (2011); p. 603 - 614, View in Reaxys 2 of 38

Comment (Pharmacological Data)

Bioactivities present

Meyer, Markus R.; Peters, Frank T.; Maurer, Hans H.; Drug Metabolism and Disposition; vol. 36; nb. 11; (2008); p. 2345 - 2354, View in Reaxys; Lin; Di Stefano; Schmitz; Hsu; Ellis; Lennard; Tucker; Cho; Drug Metabolism and Disposition; vol. 25; nb. 9; (1997); p. 1059 - 1064, View in Reaxys; Tucker; Lennard; Ellis; Woods; Cho; Lin; Hiratsuka; Schmitz; Chu; Biochemical Pharmacology; vol. 47; nb. 7; (1994); p. 1151 - 1156, View in Reaxys; Nash; Roth; Brodkin; Nichols; Gudelsky; Neuroscience Letters; vol. 177; nb. 1-2; (1994); p. 111 - 115, View in Reaxys; Oberlender; Nichols; Journal of Pharmacology and Experimental Therapeutics; vol. 255; nb. 3; (1990); p. 1098 1106, View in Reaxys; Oberlender; Nichols; Psychopharmacology; vol. 95; nb. 1; (1988); p. 71 - 76, View in Reaxys; Lyon; Glennon; Titeler; Psychopharmacology; vol. 88; nb. 4; (1986); p. 525 - 526, View in Reaxys; Nichols; Lloyd; Hoffman; Yim; Journal of Medicinal Chemistry; vol. 25; nb. 5; (1982); p. 530 - 535, View in Reaxys; Jessica H. Hartman; Steven D. Cothren; Sun-Ha Park; Chul-Ho Yun; Jerry A. Darsey; Grover P. Miller; Bioorganic & medicinal chemistry; vol. 21; nb. 13; (2013); p. 3749 - 3759, View in Reaxys; Llabres, Salome; GarciaRates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46, View in Reaxys; Taschwer, Magdalena; Seidl, Yvonne; Mohr, Stefan; Schmid, Martin G.; Chirality; vol. 26; nb. 8; (2014); p. 411 - 418, View in Reaxys; Rickli, Anna; Kopf, Simone; Hoener, Marius C; Liechti, Matthias E.; British Journal of Pharmacology; vol. 172; nb. 13; (2015); p. 3412 - 3425, View in Reaxys; Steuer, Andrea E.; Schmidhauser, Corina; Schmid, Yasmin; Rickli, Anna; Liechti, Matthias E.; Kraemer, Thomas; Drug Metabolism and Disposition; vol. 43; nb. 12; (2015); p. 1864 - 1871, View in Reaxys; Harvey, Eric L.; Baker, Lisa E.; Psychopharmacology; vol. 233; nb. 4; (2016); p. 673 - 680, View in Reaxys; Sandtner, Walter; Stockner, Thomas; Hasenhuetl, Peter S.; Partilla, John S.; Seddik, Amir; Zhang, Yuan-Wei; Cao, Jianjing; Holy, Marion; Steinkellner, Thomas; Rudnick, Gary; Baumann, Michael H.; Ecker, Gerhard F.; Newman, Amy Hauck; Sitte, Harald H.; Molecular Pharmacology; vol. 89; nb. 1; (2016); p. 165 - 175, View in Reaxys; Patent; The Board of Trustees of the University of Arkansas; Owens, Samuel M.; Carroll, Frank Ivy; Abraham, Philip; (77 pag.); US9303092; (2016); (B2) English, View in Reaxys 3 of 38

Comment (Pharmacological Data)

physiological behaviour discussed

Harvey, Eric L.; Baker, Lisa E.; Psychopharmacology; vol. 233; nb. 4; (2016); p. 673 - 680, View in Reaxys 4 of 38

Comment (Pharmacological Data)

physiological behaviour discussed

Sandtner, Walter; Stockner, Thomas; Hasenhuetl, Peter S.; Partilla, John S.; Seddik, Amir; Zhang, Yuan-Wei; Cao, Jianjing; Holy, Marion; Steinkellner, Thomas; Rudnick, Gary; Baumann, Michael H.; Ecker, Gerhard F.; Newman, Amy Hauck; Sitte, Harald H.; Molecular Pharmacology; vol. 89; nb. 1; (2016); p. 165 - 175, View in Reaxys 5 of 38

Comment (Pharmacological Data)

physiological behaviour discussed

Patent; The Board of Trustees of the University of Arkansas; Owens, Samuel M.; Carroll, Frank Ivy; Abraham, Philip; (77 pag.); US9303092; (2016); (B2) English, View in Reaxys 6 of 38

Comment (Pharmacological Data)

physiological behaviour discussed

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Rickli, Anna; Kopf, Simone; Hoener, Marius C; Liechti, Matthias E.; British Journal of Pharmacology; vol. 172; nb. 13; (2015); p. 3412 - 3425, View in Reaxys 7 of 38

Comment (Pharmacological Data)

physiological behaviour discussed

Comment (Pharmacological Data)

physiological behaviour discussed

Effect (Pharmacological Data)

receptor; activation of

Species or Test-System (Pharmacological Data)

RD-HGA16 cells; genetically modified/infected with: recombinant human TAAR1

Further Details (Pharmacological Data)

TAAR1: trace amine-associated receptor 1; effective concentration (EC); EC50 related to: human TAAR1

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

73.7 μmol/l

Lewin, Anita H.; Miller, Gregory M.; Gilmour, Brian; Bioorganic and Medicinal Chemistry; vol. 19; nb. 23; (2011); p. 7044 - 7048, View in Reaxys 10 of 38

Effect (Pharmacological Data)

receptor; activation of

Species or Test-System (Pharmacological Data)

RD-HGA16 cells; genetically modified/infected with: recombinant human TAAR1

Further Details (Pharmacological Data)

TAAR1: trace amine-associated receptor 1

Results

molecular target: human TAAR1

Lewin, Anita H.; Miller, Gregory M.; Gilmour, Brian; Bioorganic and Medicinal Chemistry; vol. 19; nb. 23; (2011); p. 7044 - 7048, View in Reaxys 11 of 38

Effect (Pharmacological Data)

receptor; activation of

Species or Test-System (Pharmacological Data)

RD-HGA16 cells; genetically modified/infected with: recombinant rhesus monkey TAAR1

Further Details (Pharmacological Data)

TAAR1: trace amine-associated receptor 1; effective concentration (EC); EC50 related to: monkey TAAR1

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

16.1 μmol/l

Lewin, Anita H.; Miller, Gregory M.; Gilmour, Brian; Bioorganic and Medicinal Chemistry; vol. 19; nb. 23; (2011); p. 7044 - 7048, View in Reaxys 12 of 38

Effect (Pharmacological Data)

receptor; activation of

Species or Test-System (Pharmacological Data)

RD-HGA16 cells; genetically modified/infected with: recombinant rhesus monkey TAAR1

Further Details (Pharmacological Data)

TAAR1: trace amine-associated receptor 1

Results

molecular target: monkey TAAR1

Lewin, Anita H.; Miller, Gregory M.; Gilmour, Brian; Bioorganic and Medicinal Chemistry; vol. 19; nb. 23; (2011); p. 7044 - 7048, View in Reaxys

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13 of 38

Effect (Pharmacological Data)

transporter expression; inhibition of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Concentration (Pharmacological Data)

10 mg/kg

Further Details (Pharmacological Data)

reduction in serotonin transporter transcript level related to: hippocampus

Type (Pharmacological Data)

reduction in serotonin transporter transcript level

Value of Type (Pharmacological Data)

Ca. 50-fold

Biezonski, Dominik K.; Meyer, Jerrold S.; Journal of Neurochemistry; vol. 112; nb. 4; (2010); p. 951 - 962, View in Reaxys 14 of 38

Effect (Pharmacological Data)

transporter expression; inhibition of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Concentration (Pharmacological Data)

10 mg/kg

Further Details (Pharmacological Data)

reduction in vesicular monoamine transporter transcript level related to: hippocampus

Type (Pharmacological Data)

reduction in vesicular monoamine transporter transcript level

Value of Type (Pharmacological Data)

Ca. 10-fold

Biezonski, Dominik K.; Meyer, Jerrold S.; Journal of Neurochemistry; vol. 112; nb. 4; (2010); p. 951 - 962, View in Reaxys 15 of 38

Effect (Pharmacological Data)

dopamine level; decrease of

Species or Test-System (Pharmacological Data)

Swiss-Webster mouse

Sex

male

Route of Application

intraperitoneal

Kind of Dosing (Pharmacological Data)

consecutive doses of 10, 20, 30 mg/kg every 2 h

Further Details (Pharmacological Data)

dopamine level measured 7 d after last injection of title comp.; mass of species: 25 - 30 g; level decrease related to: striatum

Type (Pharmacological Data)

level decrease

Value of Type (Pharmacological Data)

48 percent

Puerta, Elena; Hervias, Isabel; Goni-Allo, Beatriz; Zhang, Steven F; Jordan, Joaquin; Starkov, Anatoly A; Aguirre, Norberto; British Journal of Pharmacology; vol. 160; nb. 2; (2010); p. 233 - 245, View in Reaxys 16 of 38

Effect (Pharmacological Data)

3,4-dihydroxyphenylacetic acid level; decrease of

Species or Test-System (Pharmacological Data)

Swiss-Webster mouse

Sex

male

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Route of Application

intraperitoneal

Kind of Dosing (Pharmacological Data)

consecutive doses of 10, 20, 30 mg/kg every 2 h

Further Details (Pharmacological Data)

3,4-dihydroxyphenylacetic acid level measured 7 d after last injection of title comp.; mass of species: 25 - 30 g; level decrease related to: striatum

Type (Pharmacological Data)

level decrease

Value of Type (Pharmacological Data)

29 percent

Effect (Pharmacological Data)

homovanillic acid level; decrease of

Species or Test-System (Pharmacological Data)

Swiss-Webster mouse

Sex

male

Route of Application

intraperitoneal

Kind of Dosing (Pharmacological Data)

consecutive doses of 10, 20, 30 mg/kg every 2 h

Further Details (Pharmacological Data)

homovanillic acid level measured 7 d after last injection of title comp.; mass of species: 25 - 30 g; level decrease related to: striatum

Type (Pharmacological Data)

level decrease

Value of Type (Pharmacological Data)

30 percent

Effect (Pharmacological Data)

dopamine level; effect on

Species or Test-System (Pharmacological Data)

Swiss-Webster mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. administered three times every 2 h

Further Details (Pharmacological Data)

dopamine level measured 7 d after last injection of title comp.; mass of species: 25 - 30 g

Results

no effect (related to striatum)

Effect (Pharmacological Data)

mitochondrial electron transport chain complex I activity; effect on

Species or Test-System (Pharmacological Data)

Swiss-Webster mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

10 mg/kg

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Kind of Dosing (Pharmacological Data)

title comp. administered three times every 2 h

Further Details (Pharmacological Data)

activity measured 3 h after last injection of title comp.; mass of species: 25 - 30 g

Results

no effect (related to striatum)

Effect (Pharmacological Data)

mitochondrial electron transport chain complex II activity; effect on

Species or Test-System (Pharmacological Data)

Swiss-Webster mouse

Sex

male

Route of Application

intraperitoneal

Kind of Dosing (Pharmacological Data)

consecutive doses of 10, 20, 30 mg/kg every 2 h

Further Details (Pharmacological Data)

activity measured 1 to 24 h after last injection of title comp.; mass of species: 25 - 30 g

Results

no effect (related to striatum)

Effect (Pharmacological Data)

mitochondrial electron transport chain complex II/III activity; effect on

Species or Test-System (Pharmacological Data)

Swiss-Webster mouse

Sex

male

Route of Application

intraperitoneal

Kind of Dosing (Pharmacological Data)

consecutive doses of 10, 20, 30 mg/kg every 2 h

Further Details (Pharmacological Data)

activity measured 1 to 24 h after last injection of title comp.; mass of species: 25 - 30 g

Results

no effect (related to striatum)

Effect (Pharmacological Data)

mitochondrial electron transport chain complex IV activity; effect on

Species or Test-System (Pharmacological Data)

Swiss-Webster mouse

Sex

male

Route of Application

intraperitoneal

Kind of Dosing (Pharmacological Data)

consecutive doses of 10, 20, 30 mg/kg every 2 h

Further Details (Pharmacological Data)

activity measured 1 to 24 h after last injection of title comp.; mass of species: 25 - 30 g

Results

no effect (related to striatum)

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

membranes of E. coli expressing P450 CYP2D6, Phe120Ala

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Concentration (Pharmacological Data)

<= 200 μmol/l

Method (Pharmacological Data)

Further Details (Pharmacological Data)

NADPH regenerating system: NADPH, glucose-6-phosphate, and glucose-6-phosphate dehydrogenase

Results

Km: 4.9, 10.3, and 6.9 μmol/l for 3,4-dihydroxy-, N-dealkyl-, and N-hydroxy- oxidation products, respectively; Vmax: 2.4 min-1nmol/l-1 CYP, 3.8 min-1, and 8.4 min-1nmol/l-1 CYP for above products, respectively

Metabolite XRN (Pharmacological Data)

3251333; 150196; 10157341

Metabolite (Pharmacological Data)

(+/-)-DHMA; 3,4-methylenedioxyamphetamine; N-Hydroxy-Methylenedioxymethamphetamine

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

membranes of Escherichia coli expressing P450 CYP2D6

Concentration (Pharmacological Data)

<= 200 μmol/l

Method (Pharmacological Data)

Further Details (Pharmacological Data)

NADPH regenerating system: NADPH, glucose-6-phosphate, and glucose-6-phosphate dehydrogenase

Results

Km: 3.3 μmol/l; Vmax: 1.2 min-1nmol-1 CYP

Metabolite XRN (Pharmacological Data)

9047185

Metabolite (Pharmacological Data)

(+)-DHMA

Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

rat brain synaptosomes

Method (Pharmacological Data)

Further Details (Pharmacological Data)

reference comp.: 5-HT (5-hydroxytryptamine), EC50 > 10000 nmol/l; NE: norepinephrine

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

136 nmol/l

Effect (Pharmacological Data)

transmitter releasing

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Species or Test-System (Pharmacological Data)

rat caudate synaptosomes

Method (Pharmacological Data)

caudate homogenized and centrifuged; supernatant incubated with 5 nmol/l <3H>DA (30 min, 25 deg C), then title comp. added (5 min); liquid scintillation counting

Further Details (Pharmacological Data)

reference comp.: 5-HT (5-hydroxytryptamine), EC50 > 10000 nmol/l; DA: dopamine

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

142 nmol/l

Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

rat brain synaptosomes

Method (Pharmacological Data)

Further Details (Pharmacological Data)

reference comp.: 5-HT (5-hydroxytryptamine), EC50 = 44 nmol/l; GBR12935: (diphenylmethoxy)ethyl-4-(3-phenylpropyl)-piperazine

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

74 nmol/l

Effect (Pharmacological Data)

agonist

Species or Test-System (Pharmacological Data)

HEK293 cells

Method (Pharmacological Data)

stimulation of phosphatidylinositol hydrolysis via h5-HT2B receptors activation determined

Further Details (Pharmacological Data)

reference comp.: 5-HT (5-hydroxytryptamine), EC50: 1 nmol/l

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

6000 nmol/l

Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

human

Sex

male

Method (Pharmacological Data)

8 healthy volunteers, 22-32 years; blood samples collected from forearm vein at 0.5, 1, 2, 4, 6, 8 and 24 h after (R,S)-MDMA administration (40 mg, oral, in capsule form with ca. 200 ml water); plasma separated; GC-MS

Further Details (Pharmacological Data)

(R,S)-MDMA: (R,S)-3,4-methylenedioxymethamphetamine

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Results

mean plasma conc. of title comp. at 1h after (R,S)-MDMA administration was 8.7 μg/l

Forsling; Fallon; Kicman; Hutt; Cowan; Henry; Journal of Pharmacy and Pharmacology; vol. 53; nb. 10; (2001); p. 1357 - 1363, View in Reaxys 30 of 38

Effect (Pharmacological Data)

transport

Species or Test-System (Pharmacological Data)

rat synaptosomes

Method (Pharmacological Data)

cells from the hippocampus of ca. 150 g male CRL:CD(SD)BR rats incub. with title comp. +<3H>-5-HT in Krebs-Henseleit buffer (+2 mmol/l CaCl2; pH 7.2-7.4; 5 min; 30 deg C); radioligand uptake determined by liquid scintillation

Further Details (Pharmacological Data)

response in Ca(2+)-free sol. (+3 mmol/l EGTA) also obtained; IC50: value for Ca(2+)-containing sol.; title comp. effect on <3H>-5-HT uptake studied

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

0.35 μmol/l

Results

Ca(2+)-independent <3H>-5-HT uptake (IC50<-Ca>=0.35 μmol/l)

Crespi, Daniela; Mennini, Tiziana; Gobbi, Marco; British Journal of Pharmacology; vol. 121; nb. 8; (1997); p. 1735 - 1743, View in Reaxys 31 of 38

Effect (Pharmacological Data)

transport

Species or Test-System (Pharmacological Data)

rat synaptosomes

Method (Pharmacological Data)

cells from the striatum of ca. 150 g male CRL:CD(SD)BR rats incub. with title comp. +<3H>-dopamine (DA) in Krebs-Henseleit buffer (+2 mmol/l CaCl2; pH 7.2-7.4; 5 min; 30 deg C); radioligand uptake determined by liquid scintillation

Further Details (Pharmacological Data)

response in Ca(2+)-free sol. (+0.03 mmol/l EGTA) also obtained; IC50: value for Ca(2+)containing sol.; title comp. effect on DA uptake studied

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

1.14 μmol/l

Results

Ca(2+)-independent DA uptake (IC50<-Ca>=1.14 μmol/l)

Crespi, Daniela; Mennini, Tiziana; Gobbi, Marco; British Journal of Pharmacology; vol. 121; nb. 8; (1997); p. 1735 - 1743, View in Reaxys 32 of 38

Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

rat synaptosomes

Concentration (Pharmacological Data)

5 - 20 μmol/l

Method (Pharmacological Data)

cells from the striatum of ca. 150 g male CRL:CD(SD)BR rats loaded with <3H>-dopamine (DA) in Krebs-Henseleit buffer (+1.2 mmol/l CaCl2; O2:CO2=95:5; pH 7.2-7.4; 15 min; 37 deg C); after 42 min equilibration superfused with fresh buffer for 18 min

Further Details (Pharmacological Data)

title comp. added to buffer for 3 min; DA release induced by high KCl depolarization; response also measured in Ca(2+)-free buffer (+0.03 mmol/l EGTA); title comp. effect on DA release studied; role of Ca(2+)-channel examined using ω-agatoxin-IVA

Results

partially (31-80 percent) Ca(2+)-dependent DA release (mediated by Ca(2+)-influx through P-type Ca(2+)-channels (diagram)

Crespi, Daniela; Mennini, Tiziana; Gobbi, Marco; British Journal of Pharmacology; vol. 121; nb. 8; (1997); p. 1735 - 1743, View in Reaxys 33 of 38

Effect (Pharmacological Data)

transmitter releasing

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Species or Test-System (Pharmacological Data)

rat synaptosomes

Concentration (Pharmacological Data)

Ca. 0.15 - 10 μmol/l

Method (Pharmacological Data)

cells from the hippocampus of ca. 150 g male CRL:CD(SD)BR rats loaded with <3H>-5HT in Krebs-Henseleit buffer (+1.2 mmol/l CaCl2; O2:CO2=95:5; pH 7.2-7.4; 15 min; 37 deg C); after 42 min equilibration superfused with fresh buffer for 18 min

Further Details (Pharmacological Data)

title comp. added to buffer for 3 min; 5-HT release induced by high KCl depolarization; response also measured in Ca(2+)-free buffer (+3 mmol/l EGTA); title comp. effect on 5-HT release studied

Results

partially (31-80 percent) Ca(2+)-dependent DA release (diagram)

Crespi, Daniela; Mennini, Tiziana; Gobbi, Marco; British Journal of Pharmacology; vol. 121; nb. 8; (1997); p. 1735 - 1743, View in Reaxys 34 of 38

Effect (Pharmacological Data)

effect on core body temperature and on 5HT, 5HIAA levels

Species or Test-System (Pharmacological Data)

Holtzmann rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

40 mg/kg

Kind of Dosing (Pharmacological Data)

title compound hydrochloride dissolved in saline

Method (Pharmacological Data)

for rats (250-300 g) core temperature measurements, temperature-sensitive radio transmitters were implanted in the peritoneum of the rats; temperature measurements were made after the title comp. injection every 15 min for 4 h

Further Details (Pharmacological Data)

one week after injections, rats were sacrificed, brains were dissected, tissue samples were analysed, serotonin (5HT), 5-hydroxyindole acetic acid (5HIAA) levels determined by HPLC

Results

title compound showed a significant increase in core temp. 240 min after the injection, this hyperthermia continued until 600 min (fig. given); title comp. produced decreases in 5HT and 5-HIAA levels

Malberg, Jessica E.; Sabol, Karen E.; Seiden, Lewis S.; Journal of Pharmacology and Experimental Therapeutics; vol. 278; nb. 1; (1996); p. 258 - 267, View in Reaxys 35 of 38

Effect (Pharmacological Data)

stimulation of efflux

Species or Test-System (Pharmacological Data)

LLC-PK1 cells

Concentration (Pharmacological Data)

0.1 mmol/l

Exposure Period (Pharmacological Data)

30 min

Method (Pharmacological Data)

cells transfected with cDNA encoding rat serotonin transporter (SERT), human norepinephrine transporter (NET) or rat dopamine transporter (DAT); incubated with radiolabelled 5-HT (SERT) or 1-methyl-4-phenylpyridinium(1+) (MMP) at 37 deg C

Further Details (Pharmacological Data)

washing, 30 min incubation with title comp.; activity measured

Results

title comp. increased 5-HT efflux from SERT cells and MPP-efflux from NET and DAT cells; 50 μM mazindol decreased this effect; table and diagram given

Wall, Stephen C.; Gu, Howard; Rudnick, Gary; Molecular Pharmacology; vol. 47; nb. 3; (1995); p. 544 - 550, View in Reaxys 36 of 38

Effect (Pharmacological Data)

transporter, inhibition of

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Species or Test-System (Pharmacological Data)

LLC-PK1 cells

Exposure Period (Pharmacological Data)

4 min

Method (Pharmacological Data)

cells transfected with cDNA encoding SERT, NET or DAT; incubation with radiolabeled 5HT (SERT) or MPP(1+) (NET and DAT) and title comp. at room temp.; uptake of activity measured

Results

potent inhibitor for all three transporters; diagram given

Wall, Stephen C.; Gu, Howard; Rudnick, Gary; Molecular Pharmacology; vol. 47; nb. 3; (1995); p. 544 - 550, View in Reaxys 37 of 38

Effect (Pharmacological Data)

receptor; binding activity

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

30 mg/kg

Method (Pharmacological Data)

animals were killed, brain removed, frontal cortex and brain stem region including dorsal raphe nucleus were dissected, 5-HT and 5-HIAA determined by liquid chromatoraphy; <3H>paroxetine binding, <3H>8-OH-DPAT binding

Further Details (Pharmacological Data)

effects on somatodendritic and postsynaptic 5-HT1 receptors in the brain

Results

reduction of serotonin content, and paroxetine binding in the frontal cortex, but not in the brain stem; increase of 5-HT1A receptor number in the frontal cortex

Aguirre, Norberto; Galbete, Jose L.; Lasheras, Berta; Rio, Joaquin Del; European Journal of Pharmacology; vol. 281; nb. 1; (1995); p. 101 - 106, View in Reaxys 38 of 38

Comment (Pharmacological Data)

effect on release of <3H>serotonin from rat whole brain synaptosomes in vitro

Nichols, David E.; Lloyd, David H.; Hoffman, Andrew J.; Nichols, Maxine B.; Yim, George K. W.; Journal of Medicinal Chemistry; vol. 25; nb. 5; (1982); p. 530 - 535, View in Reaxys

Reaxys ID 5261850 View in Reaxys

H N

4/52 CAS Registry Number: 42542-10-9; 66142-89-0; 69610-10-2; 81262-70-6 Chemical Name: (-)-3,4-Methylenedioxymethamphetamine; (-)MDMA; (R)-MDMA; R-MDMA; MDMA; (R)-(-)-N-methyl-1-(1,3benzodioxol-5-yl)-2-propanamine; (R)-1-(benzo[d][1,3]dioxol-5yl)-N-methylpropan-2-amine Linear Structure Formula: C11H15NO2 Molecular Formula: C11H15NO2 Molecular Weight: 193.246 Type of Substance: heterocyclic InChI Key: SHXWCVYOXRDMCX-MRVPVSSYSA-N Note:

O O

Substance Label (4) Label References (R)-10a; (R)MDMA

R-MDMA

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R-2a: free base

Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015, View in Reaxys

(R)-(-)-2

Nichols, David E.; Lloyd, David H.; Hoffman, Andrew J.; Nichols, Maxine B.; Yim, George K. W.; Journal of Medicinal Chemistry; vol. 25; nb. 5; (1982); p. 530 - 535, View in Reaxys

Derivative (1) Derivative (R)-(-)-N-methyl-1-(1,3-benzodioxol-5-yl)-2propanamine hydrochloride

References Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015, View in Reaxys

Chromatographic Data (1) Chromatographic References data HPLC (High performance liquid chromatography)

Crystal Property Description (1) Colour & Other References Properties white

Optical Rotatory Power (1) 1 of 1

Type (Optical Rotatory Power)

[alpha]

Concentration (Optical Rotatory Power)

0.6 g/100ml

Solvent (Optical Rotatory Power)

water

Optical Rotatory Power [deg]

-12.4

Description (NMR Spec- Chemical shifts troscopy) Nucleus (NMR Spectroscopy)

Solvents (NMR Spectro- water-d2 scopy) Frequency (NMR Spectroscopy) [MHz]

400

Description (NMR Spec- Chemical shifts troscopy) Nucleus (NMR Spectroscopy)

13C

Solvents (NMR Spectro- water-d2 scopy)

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Frequency (NMR Spectroscopy) [MHz]

100

Description (NMR Spec- Spectrum troscopy) Nucleus (NMR Spectroscopy)

Solvents (NMR Spectro- various solvent(s) scopy) Frequency (NMR Spectroscopy) [MHz]

400

Comment (NMR Spectroscopy)

in the presence of organic compounds

Description (IR Spectroscopy)

Bands

Comment (IR Spectroscopy)

film

Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46, View in Reaxys Mass Spectrometry (2) Description (Mass References Spectrometry) high resolution mass spectrometry (HRMS); electrospray ionisation (ESI); spectrum

GCMS (Gas chro- Schwaninger, Andrea E.; Meyer, Markus R.; Huestis, Marilyn A.; Maurer, Hans H.; Journal of Mass Specmatography mass trometry; vol. 46; nb. 7; (2011); p. 603 - 614, View in Reaxys spectrometry); Negative chemical ionization; Spectrum Pharmacological Data (16) 1 of 16

Comment (Pharmacological Data)

Bioactivities present

Nichols, David E.; Lloyd, David H.; Hoffman, Andrew J.; Nichols, Maxine B.; Yim, George K. W.; Journal of Medicinal Chemistry; vol. 25; nb. 5; (1982); p. 530 - 535, View in Reaxys; Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015, View in Reaxys; Forsling; Fallon; Kicman; Hutt; Cowan; Henry; Journal of Pharmacy and Pharmacology; vol. 53; nb. 10; (2001); p. 1357 1363, View in Reaxys; Setola, Vincent; Hufeisen, Sandra J.; Grande-Allen, K. Jane; Vesely, Ivan; Glennon, Richard A.; Blough, Bruce; Rothman, Richard B.; Roth, Bryan L.; Molecular Pharmacology; vol. 63; nb. 6; (2003); p. 1223 - 1229, View in Reaxys; Haji-Momenian, Shahriar; Rieger, Jayson M.; Macdonald, Timothy L.; Brown, Milton L.; Bioorganic and Medicinal Chemistry; vol. 11; nb. 24; (2003); p. 5545 - 5554, View in Reaxys; Keizers, Peter H. J.; De Graaf, Chris; De Kanter, Frans J. J.; Oostenbrink, Chris; Feenstra, K. Anton; Commandeur, Jan N. M.; Vermeulen, Nico P. E.; Journal of Medicinal Chemistry; vol. 48; nb. 19; (2005); p. 6117 - 6127, View in Reaxys; Lewin, Anita H.; Miller, Gregory M.; Gilmour, Brian; Bioorganic and Medicinal Chemistry; vol. 19; nb. 23; (2011); p. 7044 - 7048, View in Reaxys; Schwaninger, Andrea E.; Meyer, Markus R.; Huestis, Marilyn A.; Maurer, Hans H.; Journal of Mass Spectrometry; vol. 46; nb. 7; (2011); p. 603 - 614, View in Reaxys; Moreno, Daniel; Grenu, Borja Diaz De; Garcia, Begona; Ibeas, Saturnino; Torroba, Tomas; Chemical Communications; vol. 48; nb. 24; (2012); p. 2994 - 2996, View in Reaxys; Meyer, Markus R.; Peters, Frank T.; Maurer, Hans H.; Drug Metabolism and Disposition; vol. 36; nb. 11; (2008); p. 2345 - 2354, View in Reaxys; Lin; Di Stefano; Schmitz;

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Hsu; Ellis; Lennard; Tucker; Cho; Drug Metabolism and Disposition; vol. 25; nb. 9; (1997); p. 1059 - 1064, View in Reaxys; Tucker; Lennard; Ellis; Woods; Cho; Lin; Hiratsuka; Schmitz; Chu; Biochemical Pharmacology; vol. 47; nb. 7; (1994); p. 1151 - 1156, View in Reaxys; Nash; Roth; Brodkin; Nichols; Gudelsky; Neuroscience Letters; vol. 177; nb. 1-2; (1994); p. 111 - 115, View in Reaxys; Oberlender; Nichols; Journal of Pharmacology and Experimental Therapeutics; vol. 255; nb. 3; (1990); p. 1098 - 1106, View in Reaxys; Oberlender; Nichols; Psychopharmacology; vol. 95; nb. 1; (1988); p. 71 - 76, View in Reaxys; Lyon; Glennon; Titeler; Psychopharmacology; vol. 88; nb. 4; (1986); p. 525 - 526, View in Reaxys; Nichols; Lloyd; Hoffman; Yim; Journal of Medicinal Chemistry; vol. 25; nb. 5; (1982); p. 530 - 535, View in Reaxys; Jessica H. Hartman; Steven D. Cothren; Sun-Ha Park; ChulHo Yun; Jerry A. Darsey; Grover P. Miller; Bioorganic & medicinal chemistry; vol. 21; nb. 13; (2013); p. 3749 3759, View in Reaxys; Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46, View in Reaxys; Taschwer, Magdalena; Seidl, Yvonne; Mohr, Stefan; Schmid, Martin G.; Chirality; vol. 26; nb. 8; (2014); p. 411 - 418, View in Reaxys 2 of 16

Comment (Pharmacological Data)

Bioactivities present

Steuer, Andrea E.; Schmidhauser, Corina; Schmid, Yasmin; Rickli, Anna; Liechti, Matthias E.; Kraemer, Thomas; Drug Metabolism and Disposition; vol. 43; nb. 12; (2015); p. 1864 - 1871, View in Reaxys; Patent; The Board of Trustees of the University of Arkansas; Owens, Samuel M.; Carroll, Frank Ivy; Abraham, Philip; (77 pag.); US9303092; (2016); (B2) English, View in Reaxys 3 of 16

Comment (Pharmacological Data)

physiological behaviour discussed

Patent; The Board of Trustees of the University of Arkansas; Owens, Samuel M.; Carroll, Frank Ivy; Abraham, Philip; (77 pag.); US9303092; (2016); (B2) English, View in Reaxys 4 of 16

Comment (Pharmacological Data)

physiological behaviour discussed

Comment (Pharmacological Data)

physiological behaviour discussed

Effect (Pharmacological Data)

receptor; activation of

Species or Test-System (Pharmacological Data)

RD-HGA16 cells; genetically modified/infected with: recombinant human TAAR1

Further Details (Pharmacological Data)

TAAR1: trace amine-associated receptor 1

Results

no effect (related to human TAAR1)

Lewin, Anita H.; Miller, Gregory M.; Gilmour, Brian; Bioorganic and Medicinal Chemistry; vol. 19; nb. 23; (2011); p. 7044 - 7048, View in Reaxys 7 of 16

Effect (Pharmacological Data)

receptor; activation of

Species or Test-System (Pharmacological Data)

RD-HGA16 cells; genetically modified/infected with: recombinant rhesus monkey TAAR1

Further Details (Pharmacological Data)

TAAR1: trace amine-associated receptor 1; effective concentration (EC); EC50 related to: monkey TAAR1

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

7.4 μmol/l

Lewin, Anita H.; Miller, Gregory M.; Gilmour, Brian; Bioorganic and Medicinal Chemistry; vol. 19; nb. 23; (2011); p. 7044 - 7048, View in Reaxys 8 of 16

Effect (Pharmacological Data)

receptor; activation of

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Species or Test-System (Pharmacological Data)

RD-HGA16 cells; genetically modified/infected with: recombinant rhesus monkey TAAR1

Further Details (Pharmacological Data)

TAAR1: trace amine-associated receptor 1

Results

molecular target: monkey TAAR1

Lewin, Anita H.; Miller, Gregory M.; Gilmour, Brian; Bioorganic and Medicinal Chemistry; vol. 19; nb. 23; (2011); p. 7044 - 7048, View in Reaxys 9 of 16

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

membranes of E. coli expressing P450 CYP2D6, Phe120Ala

Concentration (Pharmacological Data)

<= 200 μmol/l

Method (Pharmacological Data)

Further Details (Pharmacological Data)

NADPH regenerating system: NADPH, glucose-6-phosphate, and glucose-6-phosphate dehydrogenase

Results

Km: 13.2, 26.1, and 20.6 μmol/l for 3,4-dihydroxy-, N-dealkyl-, and N-hydroxy- oxidation products, respectively; Vmax: 2.4 min-1nmol/l-1 CYP, 5.9 min-1, and 10.7 min-1nmol/l-1 CYP for above products, respectively

Metabolite XRN (Pharmacological Data)

3251333; 150196; 10157341

Metabolite (Pharmacological Data)

(+/-)-DHMA; 3,4-methylenedioxyamphetamine; N-Hydroxy-Methylenedioxymethamphetamine

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

membranes of Escherichia coli expressing P450 CYP2D6

Concentration (Pharmacological Data)

<= 200 μmol/l

Method (Pharmacological Data)

Further Details (Pharmacological Data)

NADPH regenerating system: NADPH, glucose-6-phosphate, and glucose-6-phosphate dehydrogenase

Results

Km: 2.7 μmol/l; Vmax: 1.2 min-1nmol-1 CYP

Metabolite XRN (Pharmacological Data)

10156148

Metabolite (Pharmacological Data)

(-)-DHMA

Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

rat brain synaptosomes

Method (Pharmacological Data)

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Further Details (Pharmacological Data)

reference comp.: 5-HT (5-hydroxytryptamine), EC50 > 10000 nmol/l; NE: norepinephrine

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

560 nmol/l

Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

rat caudate synaptosomes

Method (Pharmacological Data)

caudate homogenized and centrifuged; supernatant incubated with 5 nmol/l <3H>DA (30 min, 25 deg C), then title comp. added (5 min); liquid scintillation counting

Further Details (Pharmacological Data)

reference comp.: 5-HT (5-hydroxytryptamine), EC50 > 10000 nmol/l; DA: dopamine

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

3700 nmol/l

Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

rat brain synaptosomes

Method (Pharmacological Data)

Further Details (Pharmacological Data)

reference comp.: 5-HT (5-hydroxytryptamine), EC50 = 44 nmol/l; GBR12935: (diphenylmethoxy)ethyl-4-(3-phenylpropyl)-piperazine

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

340 nmol/l

Effect (Pharmacological Data)

agonist

Species or Test-System (Pharmacological Data)

HEK293 cells

Method (Pharmacological Data)

stimulation of phosphatidylinositol hydrolysis via h5-HT2B receptors activation tested

Further Details (Pharmacological Data)

reference comp.: 5-HT (5-hydroxytryptamine), EC50: 1 nmol/l

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

900 nmol/l

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Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

human

Sex

male

Method (Pharmacological Data)

Further Details (Pharmacological Data)

(R,S)-MDMA: (R,S)-3,4-methylenedioxymethamphetamine

Results

mean plasma conc. of title comp. at 1h after (R,S)-MDMA administration was 12.9 μg/l

Forsling; Fallon; Kicman; Hutt; Cowan; Henry; Journal of Pharmacy and Pharmacology; vol. 53; nb. 10; (2001); p. 1357 - 1363, View in Reaxys 16 of 16

Comment (Pharmacological Data)

effect on release of <3H>serotonin from rat whole brain synaptosomes in vitro

Nichols, David E.; Lloyd, David H.; Hoffman, Andrew J.; Nichols, Maxine B.; Yim, George K. W.; Journal of Medicinal Chemistry; vol. 25; nb. 5; (1982); p. 530 - 535, View in Reaxys

Reaxys ID 6394674 View in Reaxys

H N

5/52 Chemical Name: (-)-MDMA; (-)-3,4-methylenedioxymethamphetamine; (-)3,4-methylenedioxymethamphetamine; methylenedioxymethamphetamine Linear Structure Formula: C11H15NO2 Molecular Formula: C11H15NO2 Molecular Weight: 193.246 Type of Substance: heterocyclic InChI Key: SHXWCVYOXRDMCX-UHFFFAOYSA-N Note:

O O (-)-enantiomer

Substance Label (2) Label References (-)MDMA

Chu, Teresa; Kumagai, Yoshito; DiStefano, Emma W.; Cho, Arthur K.; Biochemical Pharmacology; vol. 51; nb. 6; (1996); p. 789 - 796, View in Reaxys

11, MDMA

Kalix; Arzneimittel-Forschung/Drug Research; vol. 36; nb. 7; (1986); p. 1019 - 1021, View in Reaxys

Pharmacological Data (7) 1 of 7

Comment (Pharmacological Data)

Bioactivities present

Kalix; Arzneimittel-Forschung/Drug Research; vol. 36; nb. 7; (1986); p. 1019 - 1021, View in Reaxys; Chu, Teresa; Kumagai, Yoshito; DiStefano, Emma W.; Cho, Arthur K.; Biochemical Pharmacology; vol. 51; nb. 6; (1996); p. 789 - 796, View in Reaxys; Partilla, John S.; Dempsey, Allison G.; Nagpal, Ameet S.; Blough, Bruce E.; Baumann, Michael H.; Rothman, Richard B.; Journal of Pharmacology and Experimental Therapeutics; vol. 319; nb. 1; (2006); p. 237 - 246, View in Reaxys 2 of 7

Effect (Pharmacological Data)

monoamine transporter; interaction with

Species or Test-System (Pharmacological Data)

rat caudate putamen crude vesicular fraction

Method (Pharmacological Data)

vesicular fraction incubated with title comp. and 2 nmol/l <3H>DHTBZ for 4 h at 25 deg C; rapid filtration; liquid scintillation counting

Further Details (Pharmacological Data)

DHTBZ: dihydrotetrabenazine; VMAT2: vesicular monoamine transporter type 2; IC50 for title comp. inhibition of <3H>DHTBZ binding

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Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

> 100 μmol/l

Effect (Pharmacological Data)

monoamine transporter; interaction with

Species or Test-System (Pharmacological Data)

rat caudate putamen crude vesicular fraction

Method (Pharmacological Data)

vesicular fraction incubated with title comp. and 60 nmol/l <3H>dopamine for 5 min at 25 deg C; rapid filtration; liquid scintillation counting

Further Details (Pharmacological Data)

DHTBZ: dihydrotetrabenazine; VMAT2: vesicular monoamine transporter type 2; IC50 for title comp. inhibition of <3H>dopamine uptake

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

31.1 μmol/l

Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

rat caudate putamen crude vesicular fraction

Method (Pharmacological Data)

Further Details (Pharmacological Data)

EC50 and EMAX for title comp. inhibition of <3H>tyramine release

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

32.0 μmol/l

Results

EMAX = 78.8 percent

Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

rat caudate putamen crude vesicular fraction

Method (Pharmacological Data)

Further Details (Pharmacological Data)

EC50 and EMAX for title comp. inhibition of <3H>dopamine release

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

47 μmol/l

Results

EMAX = 65.1 percent

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Effect (Pharmacological Data)

neuroregulatoric

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 - 40 mg/kg

Kind of Dosing (Pharmacological Data)

as hydrochloride; single dose

Method (Pharmacological Data)

in vivo; effect on brain 5-HT levels assayed; rats weighed 200-250 g; 12 h light/dark cycle; kept at 23-25 deg C; food and water ad libitum; rats killed at determined times after treatment; brains removed and homogenized; 5-HT level measured by HPLC-ECD

Further Details (Pharmacological Data)

5-HT: serotonin

Results

5-HT depletion rose gradually and reached maximum between 3 and 6 h after dosage; graphical representation

Chu, Teresa; Kumagai, Yoshito; DiStefano, Emma W.; Cho, Arthur K.; Biochemical Pharmacology; vol. 51; nb. 6; (1996); p. 789 - 796, View in Reaxys 7 of 7

Comment (Pharmacological Data)

increase in the fractional rate of efflux of radioactivity from rat caudate nucleus tissue prelabeled with 3H-dopamine (at conc. 5 and 25 μmol/l)

Kalix; Arzneimittel-Forschung/Drug Research; vol. 36; nb. 7; (1986); p. 1019 - 1021, View in Reaxys

Reaxys ID 9060481 View in Reaxys

H N

6/52 Chemical Name: (+)-MDMA; (+)-3,4-methylenedioxymethamphetamine; (+)3,4-methylenedioxymethamphetamine Linear Structure Formula: C11H15NO2 Molecular Formula: C11H15NO2 Molecular Weight: 193.246 Type of Substance: heterocyclic InChI Key: SHXWCVYOXRDMCX-UHFFFAOYSA-N Note:

O O (+)-enantiomer

Substance Label (1) Label References (+)MDMA

Chu, Teresa; Kumagai, Yoshito; DiStefano, Emma W.; Cho, Arthur K.; Biochemical Pharmacology; vol. 51; nb. 6; (1996); p. 789 - 796, View in Reaxys

Pharmacological Data (14) 1 of 14

Comment (Pharmacological Data)

Bioactivities present

Chu, Teresa; Kumagai, Yoshito; DiStefano, Emma W.; Cho, Arthur K.; Biochemical Pharmacology; vol. 51; nb. 6; (1996); p. 789 - 796, View in Reaxys; Partilla, John S.; Dempsey, Allison G.; Nagpal, Ameet S.; Blough, Bruce E.; Baumann, Michael H.; Rothman, Richard B.; Journal of Pharmacology and Experimental Therapeutics; vol. 319; nb. 1; (2006); p. 237 - 246, View in Reaxys; McCreary, Andrew C.; Bankson, Michael G.; Cunningham, Kathryn A.; Journal of Pharmacology and Experimental Therapeutics; vol. 290; nb. 3; (1999); p. 965 - 973, View in Reaxys 2 of 14

Effect (Pharmacological Data)

monoamine transporter; interaction with

Species or Test-System (Pharmacological Data)

rat caudate putamen crude vesicular fraction

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Method (Pharmacological Data)

vesicular fraction incubated with title comp. and 2 nmol/l <3H>DHTBZ for 4 h at 25 deg C; rapid filtration; liquid scintillation counting

Further Details (Pharmacological Data)

DHTBZ: dihydrotetrabenazine; VMAT2: vesicular monoamine transporter type 2; IC50 for title comp. inhibition of <3H>DHTBZ binding

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

> 100 μmol/l

Effect (Pharmacological Data)

monoamine transporter; interaction with

Species or Test-System (Pharmacological Data)

rat caudate putamen crude vesicular fraction

Method (Pharmacological Data)

vesicular fraction incubated with title comp. and 60 nmol/l <3H>dopamine for 5 min at 25 deg C; rapid filtration; liquid scintillation counting

Further Details (Pharmacological Data)

DHTBZ: dihydrotetrabenazine; VMAT2: vesicular monoamine transporter type 2; IC50 for title comp. inhibition of <3H>dopamine uptake

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

22.8 μmol/l

Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

rat caudate putamen crude vesicular fraction

Concentration (Pharmacological Data)

Ca. 500 - 1000000 nmol/l

Method (Pharmacological Data)

Further Details (Pharmacological Data)

EC50 and EMAX for title comp. inhibition of <3H>tyramine release

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

69.2 μmol/l

Results

EMAX = 104 percent

Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

rat caudate putamen crude vesicular fraction

Concentration (Pharmacological Data)

Ca. 500 - 1000000 nmol/l

Method (Pharmacological Data)

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Further Details (Pharmacological Data)

EC50 and EMAX for title comp. inhibition of <3H>dopamine release

Type (Pharmacological Data)

EC50

Value of Type (Pharmacological Data)

22 μmol/l

Results

EMAX = 65.3 percent

Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

3 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. was dissolved in 0.9 percent saline

Method (Pharmacological Data)

rats injected 0.1, 0.3, 0.625, 1.25 or 2.5 mg/kg s.c. GR 127935 or 2 ml/kg 10 percent βcyclodextrin (vehicle); 45 min later title comp. injected; LA recording started in a special chamber 15 min before first injection and lasted in 5-min epochs for 90 min

Further Details (Pharmacological Data)

control: vehicle (0.9 percent saline); internal control: basal LA; LA: locomotor activity; LA recorded in inner 16 x 16 cm field counted as central, in field out of 16-cm band as peripheral; GR 127935, 5-HT(5-hydroxytryptamine)1B/1D receptor antagonist

Results

title comp. sign. increased peripheral and central activity over basal levels; rearing activity increased inconsistently; GR 127935 sign. attenuated title comp.-evoked peripheral (0.3 2.5 mg/kg) and central (0.3 - 0.625 mg/kg) LA (figures)

McCreary, Andrew C.; Bankson, Michael G.; Cunningham, Kathryn A.; Journal of Pharmacology and Experimental Therapeutics; vol. 290; nb. 3; (1999); p. 965 - 973, View in Reaxys 7 of 14

Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

3 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. was dissolved in 0.9 percent saline; rats were treated for 5 d

Method (Pharmacological Data)

rats treated for 5 d with 2.5 mg/kg s.c. GR 127935 or 10 percent β-cyclodextrin followed by title comp. injection; 48 h after last injection rats injected i.p. 2 mg/kg with RU 24969; 15 min later locomotor activity (LA) recorded for 105 min in 5-min epochs

Further Details (Pharmacological Data)

control: vehicle; internal control: basal value; LA recorded in inner 16 x 16 cm field counted as central, in field out of 16-cm band as peripheral; GR 127935, 5-HT(5-hydroxytryptamine)1B/1D receptor antagonist; RU 24969, 5-HT1B/1A receptor agonist

Results

title comp.-evoked central activity increased from day 1 to day 5; pretreatment with GR 127935 led to sign. increase in peripheral, central and rearing LA; withdrawal from title comp. was associated with hyperactivity induced by 5-HT1B/1A agonist

McCreary, Andrew C.; Bankson, Michael G.; Cunningham, Kathryn A.; Journal of Pharmacology and Experimental Therapeutics; vol. 290; nb. 3; (1999); p. 965 - 973, View in Reaxys

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8 of 14

Effect (Pharmacological Data)

transmitter releasing

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

3 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. was dissolved in 0.9 percent saline; rats were treated for 5 d

Method (Pharmacological Data)

rats treated for 5 d with 2.5 mg/kg s.c. GR 127935 or vehicle followed by title comp. injection; 48 h after last pretreatment rats injected i.p. 2 mg/kg RU 24969; 24 h later frontal cortex dissected and 5-HT and 5-HIAA content assessed using HPLC

Further Details (Pharmacological Data)

control: vehicle; GR 127935, 5-HT(5-hydroxytryptamine)1B/1D receptor antagonist; RU 24969, 5-HT1B/1A receptor agonist; 5-HIAA: 5-hydroxyindole acetic acid; HPLC: high performance liquid chromatography

Comment (Pharmacological Data)

No effect

McCreary, Andrew C.; Bankson, Michael G.; Cunningham, Kathryn A.; Journal of Pharmacology and Experimental Therapeutics; vol. 290; nb. 3; (1999); p. 965 - 973, View in Reaxys 9 of 14

Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

3 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. was dissolved in 0.9 percent saline; rats were treated for 5 d

Method (Pharmacological Data)

rats treated with 2.5 mg/kg s.c. GR 127935 or 10 percent β-cyclodextrin followed by title comp. injection for 5 d; LA recording started just after title comp. injection in 5-min epochs for 120 min; after 48 h of withdrawal rats injected i.p. 2 mg/kg RU 24969

Further Details (Pharmacological Data)

control: vehicle (1 ml/kg); internal control: basal value; LA (locomotor activity) recorded in inner 16 x 16 cm field counted as central, in field out of 16-cm band as peripheral; GR 127935, 5-HT(5-hydroxytryptamine)1B/1D receptor antagonist

Results

title comp. sign. increased peripheral and central but not rearing activity on days 1 and 5; GR 127935 sign. attenuated title comp.-evoked peripheral and central activity on day 1 and had no sign. effect on day 5 (figures)

McCreary, Andrew C.; Bankson, Michael G.; Cunningham, Kathryn A.; Journal of Pharmacology and Experimental Therapeutics; vol. 290; nb. 3; (1999); p. 965 - 973, View in Reaxys 10 of 14

Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

3 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. was dissolved in 0.9 percent saline

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Method (Pharmacological Data)

rats injected 0.5, 1 or 2 mg/kg s.c. WAY 100635 or 1 ml/kg saline; 30 min later title comp. injected; locomotor activity (LA) recording started in a special chamber 30 min before first injection and lasted in 5-min epochs for 90 min

Further Details (Pharmacological Data)

control: vehicle (0.9 percent saline); internal control: basal LA; LA recorded in inner 16 x 16 cm field counted as central, in field out of 16-cm band as peripheral; WAY 100635, selective 5-HT(5-hydroxytryptamine)1A receptor antagonist

Results

title comp. sign. increased peripheral and central activity over basal levels; there was no sign. changes in rearing activity; title comp.-evoked central activity increased after WAY 100635 (0.5 mg/kg) pretreatment (figures)

McCreary, Andrew C.; Bankson, Michael G.; Cunningham, Kathryn A.; Journal of Pharmacology and Experimental Therapeutics; vol. 290; nb. 3; (1999); p. 965 - 973, View in Reaxys 11 of 14

Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male and female

Route of Application

subcutaneous

Concentration (Pharmacological Data)

5 - 40 mg/kg

Kind of Dosing (Pharmacological Data)

as hydrochloride; single dose

Method (Pharmacological Data)

in vivo; rats weighed 200-250 g; 12 h light/dark cycle; kept at 23-25 deg C; food and water ad libitum; rats killed at determined times after treatment; blood samples collected; brains removed and homogenized

Further Details (Pharmacological Data)

title comp., MDA and 6-OHMDMA levels measured by GC-MS; DHMA levels measured by HPLC-ECD; MDA: 3,4-methylenedioxyamphetamine; DHMA: 3,4-dihydroxymethamphetamine; 6-OHMDMA: 6-hydroxy-3,4-methylenedioxymethamphetamine

Results

title comp. brain levels were higher in males; major metabolite was MDA which levels were higher in males; DHMA was detected in brain only in males after 40 mg/kg dose; 6OHMDMA was not detected in females after doses < 40 mg/kg

Metabolite XRN (Pharmacological Data)

150196; 3251333; 9051163

Metabolite (Pharmacological Data)

(R/S)-1-(3,4-methylenedioxyphenyl)-2-amino-propane; (+/-)-DHMA; 6-hydroxy-3,4-methylenedioxymethamphetamine

Chu, Teresa; Kumagai, Yoshito; DiStefano, Emma W.; Cho, Arthur K.; Biochemical Pharmacology; vol. 51; nb. 6; (1996); p. 789 - 796, View in Reaxys 12 of 14

Effect (Pharmacological Data)

neuroregulatoric

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male and female

Route of Application

subcutaneous

Concentration (Pharmacological Data)

5 - 40 mg/kg

Kind of Dosing (Pharmacological Data)

as hydrochloride; single dose

Method (Pharmacological Data)

Further Details (Pharmacological Data)

5-HT: serotonin

Results

5-HT depletion rose gradually and reached maximum between 3 and 6 h after dosage; at dose of 5/10/20/40 mg/kg title comp. decreased 5-HT level in brain by

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44.69/60.89/56.34/56.85 percent in males and by 31.25/63.15/56.71/53.9 percent in females Chu, Teresa; Kumagai, Yoshito; DiStefano, Emma W.; Cho, Arthur K.; Biochemical Pharmacology; vol. 51; nb. 6; (1996); p. 789 - 796, View in Reaxys 13 of 14

Effect (Pharmacological Data)

neuroregulatoric

Species or Test-System (Pharmacological Data)

Dark Agouti rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

5 - 40 mg/kg

Kind of Dosing (Pharmacological Data)

as hydrochloride; single dose

Method (Pharmacological Data)

in vivo; effect on brain 5-HT levels assayed; rats weighed 175-200 g; 12 h light/dark cycle; kept at 23-25 deg C; food and water ad libitum; rats killed at determined times after treatment; brains removed and homogenized; 5-HT level measured by HPLC-ECD

Further Details (Pharmacological Data)

5-HT: serotonin

Results

at dose of 5/10/20/40 mg/kg title comp. decreased 5-HT level in brain by 28.2/36.51/23.76/26.03 percent

Chu, Teresa; Kumagai, Yoshito; DiStefano, Emma W.; Cho, Arthur K.; Biochemical Pharmacology; vol. 51; nb. 6; (1996); p. 789 - 796, View in Reaxys 14 of 14

Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

Dark Agouti rat

Sex

female

Route of Application

subcutaneous

Concentration (Pharmacological Data)

5 - 40 mg/kg

Kind of Dosing (Pharmacological Data)

as hydrochloride; single dose

Method (Pharmacological Data)

in vivo; rats weighed 175-200 g; 12 h light/dark cycle; kept at 23-25 deg C; food and water ad libitum; rats killed 3 h after treatment; blood samples collected; brains removed and homogenized

Further Details (Pharmacological Data)

Results

title comp. levels in brain were 11.77/19.99/63.79/114.24 nmol/g and in plasma were 1.45/2.62/9.69/16.69 nmol/ml after doses of 5/10/20/40 mg/kg; MDA was major metabolite in brain; DHMA was not detected; 6-OHMDMA level in brain was 0.06-0.15 nmol/kg

Metabolite XRN (Pharmacological Data)

150196; 9051163

Metabolite (Pharmacological Data)

(R/S)-1-(3,4-methylenedioxyphenyl)-2-amino-propane; 6-hydroxy-3,4-methylenedioxymethamphetamine

Chu, Teresa; Kumagai, Yoshito; DiStefano, Emma W.; Cho, Arthur K.; Biochemical Pharmacology; vol. 51; nb. 6; (1996); p. 789 - 796, View in Reaxys

Reaxys ID 25856432 View in Reaxys

7/52

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Linear Structure Formula: C11H16NO2 Molecular Formula: C11H16NO2 Molecular Weight: 194.254 InChI Key: JPIDFYFKXNAGCF-UHFFFAOYSA-N Note:

H H

O O

Pharmacological Data (1) 1 of 1

Comment (Pharmacological Data)

Bioactivities present

Lewis, David F.V.; Current Medicinal Chemistry; vol. 10; nb. 19; (2003); p. 1955 - 1972, View in Reaxys

Reaxys ID 15723806 View in Reaxys

2H 2H

8/52 CAS Registry Number: 1005479-79-7 Chemical Name: d2-N-methyl-1-(3,4-methylenedioxyphenyl)-2aminopropane Linear Structure Formula: C11H13 (2)H2NO2 Molecular Formula: C11H15NO2 Molecular Weight: 195.23 InChI Key: SHXWCVYOXRDMCX-RJSZUWSASA-N Note:

H N

Patent-Specific Data (1) References Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys Pharmacological Data (2) 1 of 2

Comment (Pharmacological Data)

Bioactivities present

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys 2 of 2

Effect (Pharmacological Data)

cytochrome P450 enzyme isoform CYP2D6; inhibition of

Species or Test-System (Pharmacological Data)

cytochrome P450 enzyme isoform CYP2D6 of human

Method (Pharmacological Data)

Example 5 In vitro inhibition of human cytochrome P^n enzymesSolution A: NADPH-regenerating system[00225] To a glass tube on ice were added sequentially: 2percent aqueous solution of sodium bicarbonate (10 mL) in NADP+ (17 mg), glucose-6-phosphate (78 mg) and gIucose-6- phosphate dehydrogenase (60 units).Solution B:[00226] To a glass tube on ice were added sequentially: 0.5 M KH2PO4 (pH 7.4, 2.4 mL), water (9 mL), CYP2D6 (480 μL of 1 picomol/microliter), and 3-cyano-7- ethoxycoumarin (5 mM in 2percent acetonitrile- water, 120 microliter).[00227] Solution A was transferred to a 96-well black plate (80 microliter per well), followed by various concentrations of a solution of Nmethyl-l-[3,4-methylenedioxyphenyl]- 2-aminopropane in 20percent acetonitrile-water (20 microliter per well). The reaction was initiated by adding 100 microliter of solution B to each well of the 96-well plate. The plate was incubated for 30 minutes at 37 0C in the dark. The reaction was stopped by adding 75 microliter of stop buffer (4:1 acetonitrile-0.5 M Tris base) to each well, and the end point was measured in a fluorometer plate reader at λeX = 409 nm and λc, = 460 run. Tranylcypromine was used as positive control (IC50 2.4 micromolar). Non-isotopically enriched N-methyl-1- [3,4-methylenedioxyphenyl]-2-aminopropane has an IC50 of 3 micromolar in this assay.[00228] It has thus been found that the inhibition concentration of CYP2D6 by compound of example 5 (d2-N-methyl-l-(3,4methylenedioxyphenyl)-2-aminopropane) is 8 micromolar, the inhibition concentration of CYP2D6 by compound of example 6 (ds-N- methyl-l-(3,4-methylenedioxyphenyl)-2-aminopropane) is 8 micromolar, and the inhibition concentration of CYP2D6 by compound of example 9 (d7-N-methyl-l- (3,4- methylenedioxyphenyl)-2-aminopropane) is 30 micromolar, indicating that these compounds inhibit CYP2D6 to a lesser degree as compared to the non-isotopically enriched N-methyl-1- [3,4-methylenedioxyphenyl]-2-aminopropane.

Type (Pharmacological Data)

IC50

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Value of Type (Pharmacological Data)

8 μmol/l

Location

Page/Page column 63-64

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

Reaxys ID 15723808 View in Reaxys

9/52 CAS Registry Number: 1005479-98-0 Chemical Name: d3-N-methyl-1-(3,4-methylenedioxyphenyl)-2aminopropane Linear Structure Formula: C11H12 (2)H3NO2 Molecular Formula: C11H15NO2 Molecular Weight: 196.222 InChI Key: SHXWCVYOXRDMCX-WETBIWGRSA-N Note:

O O

Patent-Specific Data (1) Prophetic ComLocation in Patent References pound prophetic product

Page/page column 72

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

Reaxys ID 15723812 View in Reaxys

CAS Registry Number: 1005479-86-6 Chemical Name: d3-N-methyl-1-(3,4-methylenedioxyphenyl)-2aminopropane Linear Structure Formula: C11H12 (2)H3NO2 Molecular Formula: C11H15NO2 Molecular Weight: 196.222 InChI Key: SHXWCVYOXRDMCX-VSWDYIGLSA-N Note:

H N

O O

10/52

2H 2H

Patent-Specific Data (1) Prophetic ComLocation in Patent References pound prophetic product

Page/page column 16

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

Reaxys ID 15723807 View in Reaxys

2H 2H 2

11/52 CAS Registry Number: 1005479-95-7 Chemical Name: d4-N-methyl-1-(3,4-methylenedioxyphenyl)-2aminopropane Linear Structure Formula: C11H11 (2)H4NO2 Molecular Formula: C11H15NO2 Molecular Weight: 197.214 InChI Key: SHXWCVYOXRDMCX-CWUGWKFWSA-N Note:

H N

Patent-Specific Data (1) Prophetic ComLocation in Patent References pound prophetic product

Page/page column 16

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

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Reaxys ID 7538166 View in Reaxys

12/52 Chemical Name: 1-methylenedioxyphenyl-2-methyl-d3-aminopropane-1,2-d2 Linear Structure Formula: C11H10D5NO2 Molecular Formula: C11H15NO2 Molecular Weight: 198.206 Type of Substance: heterocyclic InChI Key: SHXWCVYOXRDMCX-RMOCDOLISA-N Note:

O 2H

Substance Label (1) Label References MDMA D5

Fedorova, Ganna; Randak, Tomas; Lindberg, Richard H.; Grabic, Roman; Rapid Communications in Mass Spectrometry; vol. 27; nb. 15; (2013); p. 1751 - 1762, View in Reaxys

Chromatographic Data (1) Chromatographic References data LC (Liquid chromatography)

Fedorova, Ganna; Randak, Tomas; Lindberg, Richard H.; Grabic, Roman; Rapid Communications in Mass Spectrometry; vol. 27; nb. 15; (2013); p. 1751 - 1762, View in Reaxys

Mass Spectrometry (2) Description (Mass References Spectrometry) tandem mass spectrometry; electrospray ionisation (ESI); high resolution mass spectrometry (HRMS); spectrum

Fedorova, Ganna; Randak, Tomas; Lindberg, Richard H.; Grabic, Roman; Rapid Communications in Mass Spectrometry; vol. 27; nb. 15; (2013); p. 1751 - 1762, View in Reaxys

electrospray ionisation (ESI); high resolution mass spectrometry (HRMS); spectrum

Fedorova, Ganna; Randak, Tomas; Lindberg, Richard H.; Grabic, Roman; Rapid Communications in Mass Spectrometry; vol. 27; nb. 15; (2013); p. 1751 - 1762, View in Reaxys

Reaxys ID 15723809 View in Reaxys

2H 2

O O

13/52

H N

CAS Registry Number: 1005479-81-1 Chemical Name: d5-N-methyl-1-(3,4-methylenedioxyphenyl)-2aminopropane Linear Structure Formula: C11H10 (2)H5NO2 Molecular Formula: C11H15NO2 Molecular Weight: 198.206 InChI Key: SHXWCVYOXRDMCX-RCIWAKOPSA-N Note:

Patent-Specific Data (1) References Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys Pharmacological Data (2) 1 of 2

Comment (Pharmacological Data)

Bioactivities present

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys 2 of 2

Effect (Pharmacological Data)

cytochrome P450 enzyme isoform CYP2D6; inhibition of

Species or Test-System (Pharmacological Data)

cytochrome P450 enzyme isoform CYP2D6 of human

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Method (Pharmacological Data)

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

8 μmol/l

Location

Page/Page column 63-64

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

Reaxys ID 15723811 View in Reaxys

14/52 CAS Registry Number: 1005480-17-0 Chemical Name: d5-N-methyl-1-(3,4-methylenedioxyphenyl)-2aminopropane Linear Structure Formula: C11H10 (2)H5NO2 Molecular Formula: C11H15NO2 Molecular Weight: 198.206 InChI Key: SHXWCVYOXRDMCX-WMRLCABSSA-N Note:

Patent-Specific Data (1) Prophetic ComLocation in Patent References pound prophetic product

Page/page column 73

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

Reaxys ID 15723816 View in Reaxys

15/52 CAS Registry Number: 1005480-24-9 Chemical Name: d5-N-methyl-1-(3,4-methylenedioxyphenyl)-2aminopropane Linear Structure Formula: C11H10 (2)H5NO2 Molecular Formula: C11H15NO2 Molecular Weight: 198.206 InChI Key: SHXWCVYOXRDMCX-VJKMHHICSA-N Note:

O O

Patent-Specific Data (1)

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Prophetic Compound

Location in Patent References

prophetic product

Page/page column 17

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

Reaxys ID 15723810 View in Reaxys

16/52

H N

2H 2H

CAS Registry Number: 1005480-30-7 Chemical Name: d6-N-methyl-1-(3,4-methylenedioxyphenyl)-2aminopropane Linear Structure Formula: C11H9 (2)H6NO2 Molecular Formula: C11H15NO2 Molecular Weight: 199.198 InChI Key: SHXWCVYOXRDMCX-RHVJRTOSSA-N Note:

Patent-Specific Data (1) Prophetic ComLocation in Patent References pound prophetic product

Page/page column 73

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

Reaxys ID 15723814 View in Reaxys

17/52 CAS Registry Number: 1005480-06-7 Chemical Name: d6-N-methyl-1-(3,4-methylenedioxyphenyl)-2aminopropane Linear Structure Formula: C11H9 (2)H6NO2 Molecular Formula: C11H15NO2 Molecular Weight: 199.198 InChI Key: SHXWCVYOXRDMCX-QHQVXNKMSA-N Note:

O O

2H 2H

Patent-Specific Data (1) Prophetic ComLocation in Patent References pound prophetic product

Page/page column 72

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

Reaxys ID 15723813 View in Reaxys

O O

18/52 CAS Registry Number: 1005480-34-1 Chemical Name: d7-N-methyl-1-(3,4-methylenedioxyphenyl)-2aminopropane Linear Structure Formula: C11H8 (2)H7NO2 Molecular Formula: C11H15NO2 Molecular Weight: 200.19 InChI Key: SHXWCVYOXRDMCX-FLBBHGFGSA-N Note:

2H 2

Patent-Specific Data (1) Prophetic ComLocation in Patent References pound prophetic product

Page/page column 73

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

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Reaxys ID 15723817 View in Reaxys

2H 2H

19/52

2H 2H

CAS Registry Number: 1005480-07-8 Chemical Name: d8-N-methyl-1-(3,4-methylenedioxyphenyl)-2aminopropane Linear Structure Formula: C11H7 (2)H8NO2 Molecular Formula: C11H15NO2 Molecular Weight: 201.182 InChI Key: SHXWCVYOXRDMCX-GDJMUEEISA-N Note:

2H 2H

Patent-Specific Data (1) Prophetic ComLocation in Patent References pound prophetic product

Page/page column 16

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

Reaxys ID 15723818 View in Reaxys

H N

O O

20/52

2H 2H

CAS Registry Number: 1005480-04-5 Chemical Name: d8-N-methyl-1-(3,4-methylenedioxyphenyl)-2aminopropane Linear Structure Formula: C11H7 (2)H8NO2 Molecular Formula: C11H15NO2 Molecular Weight: 201.182 InChI Key: SHXWCVYOXRDMCX-GNGSARBYSA-N Note:

Patent-Specific Data (1) Prophetic ComLocation in Patent References pound prophetic product

Page/page column 72

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

Reaxys ID 15723819 View in Reaxys

21/52

O O

CAS Registry Number: 1005481-11-7 Chemical Name: d8-N-methyl-1-(3,4-methylenedioxyphenyl)-2aminopropane Linear Structure Formula: C11H7 (2)H8NO2 Molecular Formula: C11H15NO2 Molecular Weight: 201.182 InChI Key: SHXWCVYOXRDMCX-JKVDYFNRSA-N Note:

2 2 H

2 H H 2 H

Patent-Specific Data (1) Prophetic ComLocation in Patent References pound prophetic product

Page/page column 19

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

Reaxys ID 15723815 View in Reaxys 2

H 2H

2H 2

O O

22/52 CAS Registry Number: 1005480-35-2 Chemical Name: d9-N-methyl-1-(3,4-methylenedioxyphenyl)-2aminopropane Linear Structure Formula: C11H6 (2)H9NO2 Molecular Formula: C11H15NO2

2H 2

N 2H

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Molecular Weight: 202.174 InChI Key: SHXWCVYOXRDMCX-OVRXBAIHSA-N Note: Patent-Specific Data (1) Prophetic ComLocation in Patent References pound prophetic product

Page/page column 17

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

Reaxys ID 15723823 View in Reaxys

2H 2H 2H

23/52

O O

2H2

H 2 H

CAS Registry Number: 1005481-12-8 Chemical Name: d10-N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane Linear Structure Formula: C11H5 (2)H10NO2 Molecular Formula: C11H15NO2 Molecular Weight: 203.166 InChI Key: SHXWCVYOXRDMCX-SNAGVBLRSA-N Note:

Patent-Specific Data (1) Prophetic ComLocation in Patent References pound prophetic product

Page/page column 19

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

Reaxys ID 15723820 View in Reaxys

2H 2H 2H

24/52 CAS Registry Number: 1005480-96-5 Chemical Name: d11-N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane Linear Structure Formula: C11H4 (2)H11NO2 Molecular Formula: C11H15NO2 Molecular Weight: 204.158 InChI Key: SHXWCVYOXRDMCX-VLNUKZBHSA-N Note:

O O

2H 2

Patent-Specific Data (1) Prophetic ComLocation in Patent References pound prophetic product

Page/page column 18

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

Reaxys ID 15723821 View in Reaxys

H N

O O

2 2 HH 2H

25/52

2 2H

CAS Registry Number: 1005480-93-2 Chemical Name: d11-N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane Linear Structure Formula: C11H4 (2)H11NO2 Molecular Formula: C11H15NO2 Molecular Weight: 204.158 InChI Key: SHXWCVYOXRDMCX-WSBBDBADSA-N Note:

Patent-Specific Data (1) Prophetic ComLocation in Patent References pound

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prophetic product

Page/page column 74

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

Reaxys ID 15723822 View in Reaxys

26/52

CAS Registry Number: 1005480-09-0 Chemical Name: d11-N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane Linear Structure Formula: C11H4 (2)H11NO2 Molecular Formula: C11H15NO2 Molecular Weight: 204.158 InChI Key: SHXWCVYOXRDMCX-WDKZJEHSSA-N Note:

2H 2H

Patent-Specific Data (1) Prophetic ComLocation in Patent References pound prophetic product

Page/page column 16

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

Reaxys ID 15723824 View in Reaxys

27/52

2H 2H 2H

CAS Registry Number: 1005480-75-0 Chemical Name: d12-N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane Linear Structure Formula: C11H3 (2)H12NO2 Molecular Formula: C11H15NO2 Molecular Weight: 205.15 InChI Key: SHXWCVYOXRDMCX-JIDUKDAOSA-N Note:

2H 2H

O 2H2

H 2 H

Patent-Specific Data (1) Prophetic ComLocation in Patent References pound prophetic product

Page/page column 18

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

Reaxys ID 15723825 View in Reaxys

28/52

O O

2 2 HH 2H

CAS Registry Number: 1005480-97-6 Chemical Name: d12-N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane Linear Structure Formula: C11H3 (2)H12NO2 Molecular Formula: C11H15NO2 Molecular Weight: 205.15 InChI Key: SHXWCVYOXRDMCX-MNVVXWPDSA-N Note:

2 2H

Patent-Specific Data (1) Prophetic ComLocation in Patent References pound prophetic product

Page/page column 74

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

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Reaxys ID 15723826 View in Reaxys

29/52

O O

2H2 H 2H

CAS Registry Number: 1005481-30-0 Chemical Name: d13-N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane Linear Structure Formula: C11H2 (2)H13NO2 Molecular Formula: C11H15NO2 Molecular Weight: 206.142 InChI Key: SHXWCVYOXRDMCX-TUELGDKVSA-N Note:

N 2H

Patent-Specific Data (1) Prophetic ComLocation in Patent References pound prophetic product

Page/page column 75

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

Reaxys ID 15723828 View in Reaxys

2H 2H 2H

2H 2H

O O

2H2

H 2 H

30/52 CAS Registry Number: 1005481-31-1 Chemical Name: d15-N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane Linear Structure Formula: C11 (2)H15NO2 Molecular Formula: C11H15NO2 Molecular Weight: 208.126 InChI Key: SHXWCVYOXRDMCX-XNOKBVLOSA-N Note:

2H 2H

N 2H

Patent-Specific Data (1) Prophetic ComLocation in Patent References pound prophetic product

Page/page column 75

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

Reaxys ID 6577932 View in Reaxys

H N

31/52 CAS Registry Number: 64057-70-1; 69558-31-2; 69558-32-3; 92279-84-0 Chemical Name: ecstasy hydrochloride; Methylenedioxymethamphetamine hydrochloride; (±)-MDMA hydrochloride; (+/-)ecstasy hydrochloride; (+/-)-MDMA hydrochloride; MDMA hydrochloride salt; 3,4-MDMA hydrochloride Linear Structure Formula: C11H15NO2*HCl Molecular Formula: C11H15NO2*ClH Molecular Weight: 229.707 Type of Substance: heterocyclic InChI Key: LUWHVONVCYWRMZ-UHFFFAOYSA-N Note:

H O O

Substance Label (6) Label References 1; (±)MDMA; (±)1

Del Bello, Fabio; Sakloth, Farhana; Partilla, John S.; Baumann, Michael H.; Glennon, Richard A.; Bioorganic and Medicinal Chemistry; vol. 23; nb. 17; (2015); p. 5574 - 5579, View in Reaxys

MDMA

Malmusi, Luca; Dukat, Malgorzata; Young, Richard; Teitler, Milt; Darmani, Nissar A.; Ahmad, Bashir; Smith, Carol; Glennon, Richard A.; Medicinal Chemistry Research; vol. 6; nb. 6; (1996); p. 412 - 426, View in Reaxys; Yamamoto; Nash; Gudelsky; Journal of Pharmacology and Experimental Therapeutics; vol. 273; nb. 3; (1995); p. 1063 - 1070, View in Reaxys; Broening; Bowyer; Slikker Jr.; Journal of Pharmacology and Experimental Therapeutics; vol. 275; nb. 1; (1995); p. 325 - 333, View in Reaxys; Carvalho, Marcia; Carvalho, Felix; Bastos, Maria Lourdes; Archives of Toxicology; vol. 74; nb. 12; (2001); p. 789 - 793, View in Reaxys; Wu, Dafang; Victoria Otton, S.; Inaba, Tadanobu; Kalow, Werner; Sellers, Edward M.; Biochemical Pharmacology; vol. 53; nb. 11; (1997); p. 1605 - 1612, View in Reaxys; Colado; O'Shea; Gran-

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ados; Misra; Murray; Green; British Journal of Pharmacology; vol. 121; nb. 4; (1997); p. 827 - 833, View in Reaxys; Carvalho, Marcia; Hawksworth, Gabrielle; Milhazes, Nuno; Borges, Fernanda; Monks, Terrence J.; Fernandes, Eduarda; Carvalho, Felix; Bastos, Maria; Archives of Toxicology; vol. 76; nb. 10; (2002); p. 581 - 588, View in Reaxys; Colado; Camarero; Mechan; Sanchez; Esteban; Elliott; Green; British Journal of Pharmacology; vol. 134; nb. 8; (2001); p. 1711 - 1723, View in Reaxys; Biavardi, Elisa; Menozzi, Daniela; Massera, Chiara; Dalcanale, Enrico; Federici, Stefania; Sottini, Andrea; Bergese, Paolo; Tudisco, Cristina; Condorelli, Guglielmo G.; Angewandte Chemie, International Edition; vol. 53; nb. 35; (2014); p. 9183 - 9188,6; Angewandte Chemie; vol. 126; nb. 35; (2014); p. 9337 - 9342,6, View in Reaxys MDMA*HCl

Reviriego, Felipe; Navarro, Pilar; Domenech, Antonio; Garcia-Espana, Enrique; Journal of the Chemical Society, Perkin Transactions 2; nb. 9; (2002); p. 1634 - 1638, View in Reaxys; Buchanan, Hilary A. S.; Daeid, Niamh Nic; Meier-Augenstein, Wolfram; Kemp, Helen F.; Kerr, William J.; Middleditch, Michael; Analytical Chemistry; vol. 80; nb. 9; (2008); p. 3350 - 3356, View in Reaxys

Patent; DADE BEHRING INC.; WO2005/58864; (2005); (A1) English, View in Reaxys

(+/-)-MDMA*HCl

Schechter, Martin D.; European Journal of Pharmacology; vol. 341; nb. 2-3; (1998); p. 131 - 134, View in Reaxys

M12 5806

Colado; O'Shea; Granados; Murray; Green; British Journal of Pharmacology; vol. 121; nb. 5; (1997); p. 889 - 900, View in Reaxys

Patent-Specific Data (2) References Patent; Caron, Marc G.; Sotnikova, Tatyana D.; Gainetdinov, Raul R.; US2007/27208; (2007); (A1) English, View in Reaxys Patent; DADE BEHRING INC.; WO2005/58864; (2005); (A1) English, View in Reaxys Melting Point (2) 1 of 2

Melting Point [°C]

149.85 - 151.85

Solvent (Melting Point)

diethyl ether; propan-2-ol

Morimoto, Bruce H.; Lovell, Scott; Kahr, Bart; Acta Crystallographica Section C: Crystal Structure Communications; vol. 54; nb. 2; (1998); p. 229 - 231, View in Reaxys 2 of 2

Melting Point [°C]

148 - 150

Patent; Merck; DE274350; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 12; p. 768, View in Reaxys Density (1) 1 of 1

Density [g·cm-3]

1.28

Type (Density)

crystallographic

Morimoto, Bruce H.; Lovell, Scott; Kahr, Bart; Acta Crystallographica Section C: Crystal Structure Communications; vol. 54; nb. 2; (1998); p. 229 - 231, View in Reaxys Crystal Phase (1) Description (Crys- Comment (Crystal References tal Phase) Phase) Crystal structure determination

a=9.35 Angstroem, b=7.05 Angstroem, c=18.09 Angstroem, n=4.; Temperature: 161 K. Method of determination: Single Crystal X-ray Diffraction

Morimoto, Bruce H.; Lovell, Scott; Kahr, Bart; Acta Crystallographica Section C: Crystal Structure Communications; vol. 54; nb. 2; (1998); p. 229 - 231, View in Reaxys

Crystal System (1) Crystal System References rhombic

Morimoto, Bruce H.; Lovell, Scott; Kahr, Bart; Acta Crystallographica Section C: Crystal Structure Communications; vol. 54; nb. 2; (1998); p. 229 - 231, View in Reaxys

Interatomic Distances and Angles (1) Description References Interatomic distances and angles Space Group (1) Space Group

Morimoto, Bruce H.; Lovell, Scott; Kahr, Bart; Acta Crystallographica Section C: Crystal Structure Communications; vol. 54; nb. 2; (1998); p. 229 - 231, View in Reaxys

References

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Morimoto, Bruce H.; Lovell, Scott; Kahr, Bart; Acta Crystallographica Section C: Crystal Structure Communications; vol. 54; nb. 2; (1998); p. 229 - 231, View in Reaxys

NMR Spectroscopy (3) 1 of 3

Description (NMR Spec- Chemical shifts; Spectrum troscopy) Nucleus (NMR Spectroscopy)

Solvents (NMR Spectro- d(4)-methanol scopy) Temperature (NMR Spectroscopy) [°C]

24.84

Frequency (NMR Spectroscopy) [MHz]

400

Location

supporting information

Description (NMR Spec- Chemical shifts troscopy) Nucleus (NMR Spectroscopy)

13C

Solvents (NMR Spectro- D2O scopy) Frequency (NMR Spectroscopy) [MHz]

100

Description (NMR Spec- Chemical shifts troscopy) Nucleus (NMR Spectroscopy)

Solvents (NMR Spectro- D2O scopy) Frequency (NMR Spectroscopy) [MHz]

400

Description (IR Spectroscopy)

Bands

Solvent (IR Spectroscopy)

CH2Cl2

Buchanan, Hilary A. S.; Daeid, Niamh Nic; Meier-Augenstein, Wolfram; Kemp, Helen F.; Kerr, William J.; Middleditch, Michael; Analytical Chemistry; vol. 80; nb. 9; (2008); p. 3350 - 3356, View in Reaxys Raman Spectroscopy (3) Description (Ram- Solvent (Raman an Spectroscopy) Spectroscopy) Spectrum

References Liu, Honglin; Yang, Zhilin; Meng, Lingyan; Sun, Yudie; Wang, Jie; Yang, Liangbao; Liu, Jinhuai; Tian, Zhongqun; Journal of the American Chemical Society; vol. 136; nb. 14; (2014); p. 5332 - 5341, View in Reaxys

Spectrum

solid

Leger, Marc N.; Ryder, Alan G.; Applied Spectroscopy; vol. 60; nb. 2; (2006); p. 182 193, View in Reaxys

Bands

solid

Leger, Marc N.; Ryder, Alan G.; Applied Spectroscopy; vol. 60; nb. 2; (2006); p. 182 193, View in Reaxys

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Pharmacological Data (116) 1 of 116

Comment (Pharmacological Data)

Bioactivities present

Patent; Caron, Marc G.; Sotnikova, Tatyana D.; Gainetdinov, Raul R.; US2007/27208; (2007); (A1) English, View in Reaxys; Patent; Merck; DE274350; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 12; p. 768, View in Reaxys; Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015, View in Reaxys; Morimoto, Bruce H.; Lovell, Scott; Kahr, Bart; Acta Crystallographica Section C: Crystal Structure Communications; vol. 54; nb. 2; (1998); p. 229 - 231, View in Reaxys; Malmusi, Luca; Dukat, Malgorzata; Young, Richard; Teitler, Milt; Darmani, Nissar A.; Ahmad, Bashir; Smith, Carol; Glennon, Richard A.; Medicinal Chemistry Research; vol. 6; nb. 6; (1996); p. 412 - 426, View in Reaxys; Yamamoto; Nash; Gudelsky; Journal of Pharmacology and Experimental Therapeutics; vol. 273; nb. 3; (1995); p. 1063 - 1070, View in Reaxys; Broening; Bowyer; Slikker Jr.; Journal of Pharmacology and Experimental Therapeutics; vol. 275; nb. 1; (1995); p. 325 - 333, View in Reaxys; Carvalho, Marcia; Carvalho, Felix; Bastos, Maria Lourdes; Archives of Toxicology; vol. 74; nb. 12; (2001); p. 789 - 793, View in Reaxys; Forsling; Fallon; Kicman; Hutt; Cowan; Henry; Journal of Pharmacy and Pharmacology; vol. 53; nb. 10; (2001); p. 1357 - 1363, View in Reaxys; Schechter, Martin D.; European Journal of Pharmacology; vol. 341; nb. 2-3; (1998); p. 131 - 134, View in Reaxys; Reviriego, Felipe; Navarro, Pilar; Domenech, Antonio; Garcia-Espana, Enrique; Journal of the Chemical Society, Perkin Transactions 2; nb. 9; (2002); p. 1634 - 1638, View in Reaxys; Wu, Dafang; Victoria Otton, S.; Inaba, Tadanobu; Kalow, Werner; Sellers, Edward M.; Biochemical Pharmacology; vol. 53; nb. 11; (1997); p. 1605 - 1612, View in Reaxys; Colado; O'Shea; Granados; Murray; Green; British Journal of Pharmacology; vol. 121; nb. 5; (1997); p. 889 - 900, View in Reaxys; Colado; O'Shea; Granados; Misra; Murray; Green; British Journal of Pharmacology; vol. 121; nb. 4; (1997); p. 827 - 833, View in Reaxys; Morley-Fletcher, Sara; Puopolo, Maria; Gentili, Stefano; Gerra, Gilberto; Macchia, Teodora; Laviola, Giovanni; European Journal of Pharmacology; vol. 489; nb. 1-2; (2004); p. 89 - 92, View in Reaxys; Carvalho, Marcia; Hawksworth, Gabrielle; Milhazes, Nuno; Borges, Fernanda; Monks, Terrence J.; Fernandes, Eduarda; Carvalho, Felix; Bastos, Maria; Archives of Toxicology; vol. 76; nb. 10; (2002); p. 581 - 588, View in Reaxys; Sheridan, Robert D.; Turner, Simon R.; Cooper, Graham J.; Tattersall, John E.H.; European Journal of Pharmacology; vol. 511; nb. 2-3; (2005); p. 99 - 107, View in Reaxys; Escobedo, Isabel; O'Shea, Esther; Orio, Laura; Sanchez, Veronica; Segura, Mireia; De La Torre, Rafael; Farre, Magi; Green, Alfred Richard; Colado, Maria Isabel; British Journal of Pharmacology; vol. 144; nb. 2; (2005); p. 231 - 241, View in Reaxys; Wang, Xiaoying; Baumann, Michael H.; Xu, Heng; Morales, Marisela; Rothman, Richard B.; Journal of Pharmacology and Experimental Therapeutics; vol. 314; nb. 3; (2005); p. 1002 1012, View in Reaxys; Piper, Brian J.; Vu, Huyen L.; Safain, Mina G.; Oliver, Andrew J.; Meyer, Jerrold S.; Journal of Pharmacology and Experimental Therapeutics; vol. 317; nb. 2; (2006); p. 838 - 849, View in Reaxys 2 of 116

Comment (Pharmacological Data)

Bioactivities present

Aguirre; Barrionuevo; Lasheras; Del Rio; Journal of Pharmacology and Experimental Therapeutics; vol. 286; nb. 3; (1998); p. 1159 - 1165, View in Reaxys; Leger, Marc N.; Ryder, Alan G.; Applied Spectroscopy; vol. 60; nb. 2; (2006); p. 182 - 193, View in Reaxys; Callaghan, Paul D.; Farrand, Kirsten; Salem, Abdallah; Hughes, Patrick; Daws, Lynette C.; Irvine, Rodney J.; European Journal of Pharmacology; vol. 546; nb. 1-3; (2006); p. 74 - 81, View in Reaxys; Paul Hansen; Riddle, Evan L.; Sandoval, Veronica; Brown, Jeffrey M.; Gibb, James W.; Hanson, Glen R.; Fleckenstein, Annette E.; Journal of Pharmacology and Experimental Therapeutics; vol. 300; nb. 3; (2002); p. 1093 - 1100, View in Reaxys; O'Shea, Esther; Orio, Laura; Escobedo, Isabel; Sanchez, Veronica; Camarero, Jorge; Green, Alfred Richard; Colado, Maria Isabel; British Journal of Pharmacology; vol. 148; nb. 6; (2006); p. 778 - 785, View in Reaxys; Colado; Camarero; Mechan; Sanchez; Esteban; Elliott; Green; British Journal of Pharmacology; vol. 134; nb. 8; (2001); p. 1711 - 1723, View in Reaxys; Darvesh, Altaf S.; Shankaran, Mahalakshmi; Gudelsky, Gary A.; Journal of Pharmacology and Experimental Therapeutics; vol. 301; nb. 1; (2002); p. 138 - 144, View in Reaxys; Morley, Kirsten C; Gallate, Jason E; Hunt, Glenn E; Mallet, Paul E; McGregor, Iain S; European Journal of Pharmacology; vol. 433; nb. 1; (2001); p. 91 - 99, View in Reaxys; Izco, Maria; Marchant, Ivanny; Escobedo, Isabel; Peraile, Ines; Delgado, Mercedes; Higuera-Matas, Alejandro; Olias, Oscar; Ambrosio, Emilio; O'Shea, Esther; Colado, Maria Isabel; Journal of Pharmacology and Experimental Therapeutics; vol. 322; nb. 3; (2007); p. 1003 - 1012, View in Reaxys; Van, Linh M.; Hargreaves, Judith. A.; Lennard, Martin S.; Tucker, Geoffrey T.; Rostami-Hodjegan, Amin; European Journal of Pharmaceutical Sciences; vol. 32; nb. 1; (2007); p. 8 - 16, View in Reaxys; Cho, Kyung-Ok; Kim, Seul-Ki; Rhee, Gyu Seek; Kwack, Seung Jun; Cho, Dae Hyun; Sung, Ki-Wug; Kim, Seong Yun; European Journal of Pharmacology; vol. 566; nb. 1-3; (2007); p. 120 - 123, View in Reaxys; Buchanan, Hilary A. S.; Daeid, Niamh Nic; Meier-Augenstein, Wolfram; Kemp, Helen F.; Kerr, William J.; Middleditch, Michael; Analytical Chemistry; vol. 80; nb. 9; (2008); p. 3350 - 3356, View in Reaxys; Patent; DADE BEHRING INC.; WO2005/58864; (2005); (A1) English, View in Reaxys; McClung, Jessica; Fantegrossi, William; Howell, Leonard L.; Psychopharmacology; vol. 210; nb. 1; (2010); p. 75 - 83, View in Reaxys; Barbosa, Daniel Jose; Capela, Joao Paulo; Oliveira, Jorge Ma; Silva, Renata; Ferreira, Luisa Maria; Siopa, Filipa; Branco, Paula Serio; Fernandes, Eduarda; Duarte, Jose Alberto; De Lourdes Bastos, Maria; Carvalho, Felix; British Journal of Pharmacology; vol. 165; nb. 4 B; (2012); p. 1017 - 1033, View in Reaxys; Gandy, Michael N.; McIldowie, Matthew; Lewis, Katie; Wasik, Agata M.; Salomonczyk, Danielle; Wagg, Keith; Millar, Zak A.; Tindiglia, David; Huot, Philippe; Johnston, Tom; Thiele, Sherri; Nguyen, Blake; Barnes, Nicholas M.; Brotchie, Jonathan M.; Martin-Iverson, Mathew T.; Nash, Joanne; Gordon, John; Piggott, Matthew J.; MedChemComm; vol. 1; nb. 4; (2010); p. 287 - 293, View in Reaxys; Aguirre, Norberto; Ballaz, Santiago; Lasheras, Berta; Del Rio, Joaquin; European Journal of Pharmacology; vol. 346; nb. 2-3; (1998); p. 181 - 188, View in Reaxys; Millan; Rivet; Canton; Le Marouille-Girardon; Gobert; Journal of Pharmacology and Experimental Therapeutics; vol. 264; nb. 3; (1993); p. 1364 - 1376, View in Reaxys; ; (2012); Type: Review, Lab: EFF_071212,

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Owner: EFFECT, Number: 000, Revision: 07.12.2012 00:00:00, View in Reaxys; Liu, Honglin; Yang, Zhilin; Meng, Lingyan; Sun, Yudie; Wang, Jie; Yang, Liangbao; Liu, Jinhuai; Tian, Zhongqun; Journal of the American Chemical Society; vol. 136; nb. 14; (2014); p. 5332 - 5341, View in Reaxys 3 of 116

Comment (Pharmacological Data)

Bioactivities present

Biavardi, Elisa; Menozzi, Daniela; Massera, Chiara; Dalcanale, Enrico; Federici, Stefania; Sottini, Andrea; Bergese, Paolo; Tudisco, Cristina; Condorelli, Guglielmo G.; Angewandte Chemie, International Edition; vol. 53; nb. 35; (2014); p. 9183 - 9188,6; Angewandte Chemie; vol. 126; nb. 35; (2014); p. 9337 - 9342,6, View in Reaxys; Del Bello, Fabio; Sakloth, Farhana; Partilla, John S.; Baumann, Michael H.; Glennon, Richard A.; Bioorganic and Medicinal Chemistry; vol. 23; nb. 17; (2015); p. 5574 - 5579, View in Reaxys 4 of 116

Comment (Pharmacological Data)

physiological behaviour discussed

Del Bello, Fabio; Sakloth, Farhana; Partilla, John S.; Baumann, Michael H.; Glennon, Richard A.; Bioorganic and Medicinal Chemistry; vol. 23; nb. 17; (2015); p. 5574 - 5579, View in Reaxys 5 of 116

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

brain synaptosomes of mouse

Metabolite XRN (Pharmacological Data)

2088428; 3251333; 8459309

Metabolite (Pharmacological Data)

α-methyldopamine; (+/-)-DHMA; 5-(GSH)-α-MeDA

Barbosa, Daniel Jose; Capela, Joao Paulo; Oliveira, Jorge Ma; Silva, Renata; Ferreira, Luisa Maria; Siopa, Filipa; Branco, Paula Serio; Fernandes, Eduarda; Duarte, Jose Alberto; De Lourdes Bastos, Maria; Carvalho, Felix; British Journal of Pharmacology; vol. 165; nb. 4 B; (2012); p. 1017 - 1033, View in Reaxys 6 of 116

Effect (Pharmacological Data)

peroxide formation; increase of

Species or Test-System (Pharmacological Data)

brain synaptosomes of mouse

Concentration (Pharmacological Data)

6.25 - 200 μmol/l

Further Details (Pharmacological Data)

amplex red method

Results

no effect; insignificant effect(s) discussed

Effect (Pharmacological Data)

quinoprotein formation; induction of

Species or Test-System (Pharmacological Data)

brain synaptosomes of mouse

Concentration (Pharmacological Data)

6.25 - 200 μmol/l

Further Details (Pharmacological Data)

NBT/glycinate colorimetric assay

Results

no effect

Effect (Pharmacological Data)

reinstate response to amphetamine self-administration; induction of

Species or Test-System (Pharmacological Data)

Macaca mulatta, rhesus monkey

Sex

male and female

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Route of Application

intravenous

Concentration (Pharmacological Data)

0.03 - 0.1 mg/kg

Further Details (Pharmacological Data)

peak response rates induced by an amphetamine prime = 0.33 responses/s; mass of species: 8 - 15 kg

Type (Pharmacological Data)

peak response rate

Value of Type (Pharmacological Data)

61 percent

McClung, Jessica; Fantegrossi, William; Howell, Leonard L.; Psychopharmacology; vol. 210; nb. 1; (2010); p. 75 - 83, View in Reaxys 9 of 116

Effect (Pharmacological Data)

reinstate response to amphetamine self-administration; attenuation of

Species or Test-System (Pharmacological Data)

Macaca mulatta, rhesus monkey

Sex

male and female

Route of Application

intravenous

Concentration (Pharmacological Data)

0.03 - 0.1 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. administered after pre-treatment with fluoxetine (1 - 3 mg/kg)

Further Details (Pharmacological Data)

mass of species: 8 - 15 kg

Type (Pharmacological Data)

reduction rate

Value of Type (Pharmacological Data)

77 - 70 percent

McClung, Jessica; Fantegrossi, William; Howell, Leonard L.; Psychopharmacology; vol. 210; nb. 1; (2010); p. 75 - 83, View in Reaxys 10 of 116

Effect (Pharmacological Data)

drug dependence

Species or Test-System (Pharmacological Data)

C57BL/6J mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

30 mg/kg

Kind of Dosing (Pharmacological Data)

three times with 3-h interval; dissolved in 0.9 w/v NaCl (saline), given in volume of 10 ml/kg

Method (Pharmacological Data)

3 days after title comp. treatment, mice given access to voluntary consumption of ethanol (conc. increased every 7 days, 3-20percent); ethanol consumption and preference examined by two-bottle free-choice paradigm

Further Details (Pharmacological Data)

control: saline

Results

title comp. increased ethanol consumption and preference; fig.

Izco, Maria; Marchant, Ivanny; Escobedo, Isabel; Peraile, Ines; Delgado, Mercedes; Higuera-Matas, Alejandro; Olias, Oscar; Ambrosio, Emilio; O'Shea, Esther; Colado, Maria Isabel; Journal of Pharmacology and Experimental Therapeutics; vol. 322; nb. 3; (2007); p. 1003 - 1012, View in Reaxys 11 of 116

Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

C57BL/6J mouse

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Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

30 mg/kg

Kind of Dosing (Pharmacological Data)

three times with 3-h interval; dissolved in 0.9 w/v NaCl (saline), given in volume of 10 ml/kg

Method (Pharmacological Data)

7 days after title comp. treatment, mice given access to voluntary consumption of quinine solution (0.03 and 0.1 mM) for 4 days; consumption and preference examined by two-bottle free-choice paradigm

Further Details (Pharmacological Data)

control: saline

Comment (Pharmacological Data)

No effect

Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

C57BL/6J mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

30 mg/kg

Kind of Dosing (Pharmacological Data)

three times with 3-h interval; dissolved in 0.9 w/v NaCl (saline), given in volume of 10 ml/kg

Method (Pharmacological Data)

7 days after title comp. treatment, mice given access to voluntary consumption of sucrose solution (0.017-4.25percent) for 4 days; consumption and preference examined by twobottle free-choice paradigm

Further Details (Pharmacological Data)

control: saline

Comment (Pharmacological Data)

No effect

Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

C57BL/6J mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

30 mg/kg

Kind of Dosing (Pharmacological Data)

three times with 3-h interval; dissolved in 0.9 w/v NaCl (saline), given in volume of 10 ml/kg

Method (Pharmacological Data)

3 weeks after title comp. treatment, mice received ethanol (1 g/kg); locomotor activity det. in open arena, total number of photocell beam breaks counted for 30 min

Further Details (Pharmacological Data)

control: saline

Comment (Pharmacological Data)

No effect

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Effect (Pharmacological Data)

anxiolytic

Species or Test-System (Pharmacological Data)

C57BL/6J mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

30 mg/kg

Kind of Dosing (Pharmacological Data)

three times with 3-h interval; dissolved in 0.9 w/v NaCl (saline), given in volume of 10 ml/kg

Method (Pharmacological Data)

3 weeks after title comp. treatment, mice tested using light-dark box test, latency to first transition, total time spent in each compartment and number of transitions between two compartments scored

Further Details (Pharmacological Data)

control: saline

Comment (Pharmacological Data)

No effect

Effect (Pharmacological Data)

transmitter release; inhibition of

Species or Test-System (Pharmacological Data)

C57BL/6J mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

30 mg/kg

Kind of Dosing (Pharmacological Data)

three times with 3-h interval; dissolved in 0.9 w/v NaCl (saline), given in volume of 10 ml/kg

Method (Pharmacological Data)

6 weeks after title comp. treatment, microdialysis probe implanted into nucleus accumbens; 24 h later mice received ethanol (3 g/kg); dopamine and its metabolites det. by HPLC with electrochemical detection

Further Details (Pharmacological Data)

control: saline

Results

title comp. abolished ethanol-induced release of dopamine; fig.

Effect (Pharmacological Data)

transmitter release; inhibition of

Species or Test-System (Pharmacological Data)

C57BL/6J mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

30 mg/kg

Kind of Dosing (Pharmacological Data)

three times with 3-h interval; dissolved in 0.9 w/v NaCl (saline), given in volume of 10 ml/kg

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Method (Pharmacological Data)

mice received title comp., 7 days later mice given access to water or weekly increasing doses of ethanol (3-20percent) for 4 weeks; dopamine and its metabolites in striatum det. by HPLC with electrochemical detection

Further Details (Pharmacological Data)

control: saline

Results

title comp. decreased dopamine content by 56percent and homovanillic acid and DOPAC levels by ca. 30percent, effect not different in water- or ethanol-exposed animals; fig.

Effect (Pharmacological Data)

receptor density; increase of

Species or Test-System (Pharmacological Data)

C57BL/6J mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

30 mg/kg

Kind of Dosing (Pharmacological Data)

three times with 3-h interval; dissolved in 0.9 w/v NaCl (saline), given in volume of 10 ml/kg

Method (Pharmacological Data)

1 or 4 weeks after title comp. treatment, D1 and D2 receptor density in caudate-putamen, shell and core of nucleus accumbens det. by <3H>SCH23390 and <3H>YM09151-2 binding and autoradiography

Further Details (Pharmacological Data)

control: saline

Results

title comp. increased D1 receptor density in caudate-putamen and core of nucleus accumbens after 7 days; fig.

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

SuperosomesTM expressing human recombinant CYP2D6

Concentration (Pharmacological Data)

2 - 20 μmol/l

Method (Pharmacological Data)

title comp. pre-incubated with NADPH-generating system; equilibrated (37 deg C, 10 min); enzyme added; samples removed at 0-5 min and added to NADPH-generating soln. and DEX; reaction stopped; dextrorphan formation detd. by HPLC; enzyme activity detd.

Further Details (Pharmacological Data)

formation of dextrorphan from DEX was used as specific marker of CYP2D6 activity; DEX: dextromethorpan

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

2.40 μmol/l

Results

title comp. conc.- and time dependently inhibited CYP2D6; extent of inhibition increased with pre-incubation time from 0 to 2.5 min but not from 2.5 to 5 min; fig., table

Van, Linh M.; Hargreaves, Judith. A.; Lennard, Martin S.; Tucker, Geoffrey T.; Rostami-Hodjegan, Amin; European Journal of Pharmaceutical Sciences; vol. 32; nb. 1; (2007); p. 8 - 16, View in Reaxys 19 of 116

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

microsomes from Saccharomyces cerevisiae expressing hrCYP2D6

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Concentration (Pharmacological Data)

2 - 20 μmol/l

Method (Pharmacological Data)

Further Details (Pharmacological Data)

hrCYP2D6: human recombinant CYP2D6; formation of dextrorphan from DEX was used as specific marker of CYP2D6 activity; DEX: dextromethorpan

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

2.77 μmol/l

Results

title comp. conc.- and time-dependently inhibited CYP2D6; extent of inhibition increased with pre-incubation time from 0 to 2.5 min but not from 2.5 to 5 min; fig., table

Effect (Pharmacological Data)

enzyme activity; inhibtion of

Species or Test-System (Pharmacological Data)

BactosomesTM expressing human recombinant CYP2D6

Concentration (Pharmacological Data)

2 - 20 μmol/l

Method (Pharmacological Data)

Further Details (Pharmacological Data)

formation of dextrorphan from DEX was used as specific marker of CYP2D6 activity; DEX: dextromethorpan

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

6.79 μmol/l

Results

title comp. conc.- and time-dependently inhibited CYP2D6; extent of inhibition increased with pre-incubation time from 0 to 2.5 min but not from 2.5 to 5 min; fig., table

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

SuperosomesTM expressing human recombinant CYP2D6

Concentration (Pharmacological Data)

2 - 20 μmol/l

Method (Pharmacological Data)

Further Details (Pharmacological Data)

KI: title comp. conc. associated with half maximal rate of inactivation; formation of dextrorphan from DEX was used as specific marker of CYP2D6 activity; DEX: dextromethorpan

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

3.66 μmol/l

Effect (Pharmacological Data)

enzyme activity; inhibtion of

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Species or Test-System (Pharmacological Data)

microsomes from Saccharomyces cerevisiae expressing hrCYP2D6

Concentration (Pharmacological Data)

2 - 20 μmol/l

Method (Pharmacological Data)

Further Details (Pharmacological Data)

formation of dextrorphan from DEX was used as specific marker of CYP2D6 activity; DEX: dextromethorpan; hrCYP2D6: human recombinant CYP2D6

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

2.86 μmol/l

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

BactosomesTM expressing human recombinant CYP2D6

Concentration (Pharmacological Data)

2 - 20 μmol/l

Method (Pharmacological Data)

Further Details (Pharmacological Data)

formation of dextrorphan from DEX was used as specific marker of CYP2D6 activity; DEX: dextromethorpan

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

42.9 μmol/l

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

SuperosomesTM expressing human recombinant CYP2D6

Concentration (Pharmacological Data)

2 - 20 μmol/l

Method (Pharmacological Data)

enzyme incubated with NADPH-generating system and title comp. for 5 min; reaction quenched immediately or after 2.5 or 5 min; title comp. conc. measured using HPLC

Further Details (Pharmacological Data)

further study: effect of dextromethorpan on title comp. metabolism

Results

signif. metabolism of title comp. was observed particularly at low conc. when it was complete by 5 min; dextromethorpan blocked the metabolism of title comp. except at highest conc. of title comp. studied; fig.

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

microsomes from Saccharomyces cerevisiae expressing hrCYP2D6

Concentration (Pharmacological Data)

2 - 20 μmol/l

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Method (Pharmacological Data)

microsomes incubated with NADPH-generating system and title comp. for 5 min; reaction quenched immediately or after 2.5 or 5 min; title comp. conc. measured with HPLC

Further Details (Pharmacological Data)

hrCYP2D6: human recombinant CYP2D6; further study: effect of dextromethorpan on title comp. metabolism

Results

metabolism of title comp. was observed; dextromethorpan blocked the metabolism of title comp. except at highest conc. of title comp. studied; fig.

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

BactosomesTM expressing human recombinant CYP2D6

Concentration (Pharmacological Data)

2 - 20 μmol/l

Method (Pharmacological Data)

microsomes incubated with NADPH-generating system and increasing conc. title comp. for 5 min; reaction quenched immediately or after 2.5 or 5 min; title comp. conc. measured with HPLC

Further Details (Pharmacological Data)

further study: effect of dextromethorpan on title comp. metabolism

Results

metabolism of title comp. was observed; metabolism of title comp. observed in presence of dextromethorpan; fig.

Effect (Pharmacological Data)

metabolism; inhibition of

Species or Test-System (Pharmacological Data)

SuperosomesTM expressing human recombinant CYP2D6

Concentration (Pharmacological Data)

2 - 20 μmol/l

Method (Pharmacological Data)

enzyme incubated with NADPH-generating system, title comp. and dextromethorpan (5 and 50 μM); reaction quenched after 2-20 min; samples assayed for dextrophan using HPLC

Results

title comp. caused conc.-dependent decrease in dextrorphan formation at both dextromethorpan conc.; fig.

Effect (Pharmacological Data)

metabolism; inhibition of

Species or Test-System (Pharmacological Data)

microsomes of Saccharomyces cerevisiae expressing hrCYP2D6

Concentration (Pharmacological Data)

2 - 20 μmol/l

Method (Pharmacological Data)

microsomes incubated with NADPH-generating system, title comp. and dextromethorpan (5 and 50 μM); reaction quenched after 2-20 min; samples assayed for dextrophan using HPLC

Further Details (Pharmacological Data)

hrCYP2D6: human recombinant CYP2D6

Results

title comp. caused conc.-dependent decrease in dextrorphan formation at both dextromethorpan conc.; fig.

Effect (Pharmacological Data)

metabolism; inhibition of

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Species or Test-System (Pharmacological Data)

BactosomesTM expressing human recombinant CYP2D6

Concentration (Pharmacological Data)

2 - 20 μmol/l

Method (Pharmacological Data)

enzyme incubated with NADPH-generating system, title comp. and dextromethorpan (5 and 50 μM); reaction quenched after 2-20 min; samples assayed for dextrophan using HPLC

Results

title comp. caused conc.-dependent decrease in dextrorphan formation at both dextromethorpan conc.; fig.

Effect (Pharmacological Data)

antiproliferative

Species or Test-System (Pharmacological Data)

C57BL/6 mouse

Sex

female

Route of Application

peroral

Concentration (Pharmacological Data)

> 5 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. administered daily for 30 days

Method (Pharmacological Data)

mice admin. with title comp.; 1 day after last dose, BrdU administered for 4 days; 24 hour later, euthanized; brains examined; perfused; DNA denatured; sections incubated with BrdU; BrdU labeled cells in the dentate gyrus counted in a light microscope

Further Details (Pharmacological Data)

BrdU: 5-bromo-2'-deoxyuridine

Results

title comp. dose-dependently induced a decrease in the number of BrdU-positive cells in the dentate gyrus; fig.

Cho, Kyung-Ok; Kim, Seul-Ki; Rhee, Gyu Seek; Kwack, Seung Jun; Cho, Dae Hyun; Sung, Ki-Wug; Kim, Seong Yun; European Journal of Pharmacology; vol. 566; nb. 1-3; (2007); p. 120 - 123, View in Reaxys 31 of 116

Effect (Pharmacological Data)

antiproliferative

Species or Test-System (Pharmacological Data)

C57BL/6 mouse

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

> 20 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. administered daily for 30 days

Method (Pharmacological Data)

Further Details (Pharmacological Data)

BrdU: 5-bromo-2'-deoxyuridine

Results

title comp. exposure decreases cell proliferation rates in the dentate gyrus in a dose dependent manner; fig.

Effect (Pharmacological Data)

locomotor behaviors; effect on

Species or Test-System (Pharmacological Data)

DAT-KO mouse

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Sex

male and female

Method (Pharmacological Data)

Experimental We report here that the pharmacologic inhibition of the rate-limiting enzyme of DA synthesis, TH, almost immediately depletes brain DA to undetectable levels in DATKO mice and induces a transient recapitulation of essentially all PD symptoms for up to 16 h. DA-deficient DAT-KO mice (DDD mice) thus represent an acute PD model that is useful for studying the efficacy of compounds that potentially can restore control of locomotion in the absence of any contribution of the dopaminergic system. By using this approach, we found that several amphetamine derivatives can counteract the behavioral manifestations of severe DA deficiency, suggesting that, in addition to well-known DA-mediated effects, amphetamine-like compounds can also affect motor functions in a DA- and DAT-independent manner. Materials and Methods Animals. DAT-KO mice were generated as previously described [11]. Animal care was in accordance with the Guide for Care and Use of Laboratory Animals (National Institutes of Health publication No.865-23, Bethesda, Md., United States) with an approved protocol from the Duke University Institutional Animal Care and Use Committee. C57BL/6J3129Sv/J hybrid WT and DAT-KO mice, 3-5 mo old, of both sexes were used. None of animals used in these studies had the neurodegenerative phenotype sporadically observed in DAT-KO mice [60]. Drugs. Drugs or saline (0.9percent NaCl) were administered intraperitoneally (IP) or subcutaneously (SC) in a volume of 10 ml/kg. The drags were either from Sigma (St. Louis, Mo., United States) or supplied by the National Institute of Drug Abuse (NIDA). Drugs provided by the NIDA Drug Supply Program included: (+/-)-MDMA, (+)-MDMA, (+/-)-6-OH-MDA, (+/-)-MDA, (+/-)-MDE, (+)-MDE, (-)-MDE, and AFT (alpha-ethyl-tryptamine acetate). Neurochemical assessments. Striatal tissue contents of DA and frontal cortical tissue levels of NE were assessed using HPLCEC (high performance liquid chromatography with electrochemical detection) as described [8]. In vivo microdialysis measurements of striatal extracellular DA levels in freely moving mice were performed at least 24 h after implantation of a microdialysis probe as described previously [50]. Dialysate samples were assayed for DA using HPLC-EC. Behavioral methods. Locomotor activity of littermate WT and DATKO mice was measured in an Omnitech CCDigiscan (Accuscan Instruments, Columbus, Ohio United States) activity monitor under bright illumination [83]. All behavioral experiments were performed between 10:00 AM and 5:00 PM. Activity was measured at 5-min intervals, To evaluate the effects of drugs on motor behaviors, mice were placed into activity monitor chambers (20.x.20 cm) for 30 min and then treated with αMT (250 mg/kg IP). A drug or combination of drugs were injected 1 h after αMT administration, and various parameters of locomotor activity were monitored for up to 3 h. In cumulative dosing experiments, animals were treated with increasing doses of drugs after a 1-h interval. For the akinesia test, the mouse is held by the tail so that it is standing on forelimbs only and moving on its own. The number of steps taken with both forelimbs was recorded during a 30-s trial [57]. The presence of catalepsy was determined and measured by placing the animal's forepaws on a horizontal wooden bar (0.7 cm in diameter), 4 cm above the tabletop. The time until the mouse removed both forepaws from the bar was recorded, with a maximum cut-off time of 3 min [53]. In the grasping test of muscular rigidity, the mouse is suspended by its forelimbs on a metal rod (diameter: 0.25 cm) positioned approximately 20 cm above the table. The time the animal remains on the rod (maximum 1 min) was noted [58]. To assess rigidity in a bracing task, the number of steps taken with each forelimb when the mouse is pushed sideways over a distance of 50 cm was recorded [57]. Tremor was scored visually in mice using the rating scale [54]: 0, no tremor; 1, occasional isolated twi

Results

Akinesia test: ~18-35 number of steps; at Catalepsy test: ~50-180sec; at Grasping test: ~1-45 seconds time spent on the rod of the title compound administered after 1h of αMT treatment; figure is given

Location

Page/Page column 3; 12-15; sheet 9

Patent; Caron, Marc G.; Sotnikova, Tatyana D.; Gainetdinov, Raul R.; US2007/27208; (2007); (A1) English, View in Reaxys 33 of 116

Effect (Pharmacological Data)

core temperature; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

administered two times per day every 5-th day from postnatal day 35 to day 60; doses were separated by 4 h

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Method (Pharmacological Data)

rats were treated with title comp., the effect on core temperature during treatment determined

Further Details (Pharmacological Data)

control: saline

Results

on day 35 title comp. induced an initial hypothermia followed by a small elevation in temperature; on days 45 and 60 the effect was unidirectional: title comp. increased core temperature until 240 min after the first administration

Piper, Brian J.; Vu, Huyen L.; Safain, Mina G.; Oliver, Andrew J.; Meyer, Jerrold S.; Journal of Pharmacology and Experimental Therapeutics; vol. 317; nb. 2; (2006); p. 838 - 849, View in Reaxys 34 of 116

Effect (Pharmacological Data)

core temperature; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

administered two times per day every 5-th day from PD 35 to PD 60; doses were separated by 4 h

Method (Pharmacological Data)

rats were treated with title comp. on PD 35-60 and then challenged with four 5 or 10 mg/kg doses of title comp. on PD 67; the effect on core temperature determined

Further Details (Pharmacological Data)

control: saline; PD: postnatal day

Results

adolescent treatment with title comp. on PD 35-60 significantly attenuated the hyperthermic response to 10 mg/kg dose of title comp. on PD 67; the effect on hyperthermic response to 5 mg/kg dose of title comp. was insignificant

Effect (Pharmacological Data)

core temperature; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

administered two times per day every 5-th day from PD 35 to PD 60; doses were separated by 4 h

Method (Pharmacological Data)

rats were treated with title comp. on PD 35-60 and then injected with 8-OH-DPAT (0.1 or 0.5 mg/kg, s.c.) on PD 67; core temperature measured before and 15-100 min after injection

Further Details (Pharmacological Data)

control: saline; PD: postnatal day; 8-OH-DPAT: 8-hydroxy-2-(di-n-propylamino)tetralin

Comment (Pharmacological Data)

No effect

Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

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Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

administered two times per day every 5-th day from PD 35 to PD 60; doses were separated by 4 h

Method (Pharmacological Data)

rats were treated with title comp. on PD 35-60 and then injected with 8-OH-DPAT (0.1 or 0.5 mg/kg, s.c.) on PD 67; the effect on components of 5-HT syndrome determined

Further Details (Pharmacological Data)

control: saline; PD: postnatal day; 8-OH-DPAT: 8-hydroxy-2-(di-n-propylamino)tetralin; 5HT: 5-hydroxytryptamine; components of 5-HT syndrome: head-weaving, forepaw-treading and low body posture

Results

adolescent treatment with title comp. on PD 35-60 significantly reduced the 5-HT syndrome response to the high but not the low dose of 8-OH-DPAT

Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

administered two times per day every 5-th day from PD 35 to PD 60; doses were separated by 4 h

Method (Pharmacological Data)

rats were treated with title comp. on PD 35-60 and then challenged with four 5 or 10 mg/kg (hourly for 4 h) doses of title comp. on PD 67; the effect on head-weaving and forepaw-treading components of 5-HT syndrome analyzed for 5 h during dosing

Further Details (Pharmacological Data)

control: saline; PD: postnatal day; 5-HT: 5-hydroxytryptamine

Results

adolescent treatment with title comp. on PD 35-60 had no effect on the increase in total serotonin syndrome scores induced by challenge doses on PD 67

Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

administered two times per day every 5-th day from PD 35 to PD 60; doses were separated by 4 h

Method (Pharmacological Data)

rats were treated with title comp. on PD 35-60 and then challenged with four 5 or 10 mg/kg (hourly for 4 h) doses of title comp. on PD 67; the effect on the percentage of ejaculating animals and the latency to seminal discharge analyzed

Further Details (Pharmacological Data)

control: saline; PD: postnatal day

Results

adolescent treatment with title comp. on PD 35-60 had no effect on the increase in percentage of ejaculating animals induced by challenge doses on PD 67

Piper, Brian J.; Vu, Huyen L.; Safain, Mina G.; Oliver, Andrew J.; Meyer, Jerrold S.; Journal of Pharmacology and Experimental Therapeutics; vol. 317; nb. 2; (2006); p. 838 - 849, View in Reaxys

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39 of 116

Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

administered two times per day every 5-th day from PD 35 to PD 60; doses were separated by 4 h

Method (Pharmacological Data)

rats were treated with title comp. on PD 35-60 and then challenged with four 5 or 10 mg/kg (hourly for 4 h) doses of title comp. on PD 67; the effect on motor activity assessed on next day

Further Details (Pharmacological Data)

control: saline; PD: postnatal day

Results

adolescent treatment with title comp. on PD 35-60 completely prevented motor hypoactivity induced by challenge doses on PD 67

Effect (Pharmacological Data)

binding; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

administered two times per day every 5-th day from PD 35 to PD 60; doses were separated by 4 h

Method (Pharmacological Data)

rats were treated with title comp. on PD 35-60 and then challenged with four 5 or 10 mg/kg (hourly for 4 h) doses of title comp. on PD 67; animals were sacrificed on PD 74, <3H>citalopram (1 nmol/l) binding to SERT in various brain regions was performed

Further Details (Pharmacological Data)

control: saline; PD: postnatal day; SERT: serotonin transporter; binding experiments were performed for cortex, striatum and hippocampus

Results

adolescent treatment with title comp. on PD 35-60 prevented the decreases in SERT binding in cortex, striatum and hippocampus induced by challenge doses on PD 67

Effect (Pharmacological Data)

toxicity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

administered two times per day every 5-th day from PD 35 to PD 60; doses were separated by 4 h

Method (Pharmacological Data)

rats were treated with title comp. on PD 35-60 and then challenged with four 5 or 10 mg/kg doses of title comp. on PD 67; the effect on body weight determined

Further Details (Pharmacological Data)

control: saline; PD: postnatal day

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Results

5 and 10 mg/kg title comp. binge on day 67 resulted in a 7 to 9 percent loss in body weight; the effect was observed both in groups treated with title comp. and saline during adolescent period (PD 35-60)

Effect (Pharmacological Data)

toxicity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

administered two times per day every 5-th day from postnatal day 35 to day 60; doses were separated by 4 h

Method (Pharmacological Data)

rats were treated with title comp., the effect on body weight during treatment determined

Further Details (Pharmacological Data)

control: saline

Results

title comp. decreased body weight, the effect was already discernible on day 40

Effect (Pharmacological Data)

binding; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

administered two times per day every 5-th day from PD 35 to PD 60; doses were separated by 4 h

Method (Pharmacological Data)

rats were treated with title comp. and sacrificed on PD 68, 5-HT1A receptor density in frontal cortex, hippocampus, brainstem and lumbar spinal cord was determined by measuring the binding of <3H>WAY-100635 (0.5 nmol/l) to membrane fractions

Further Details (Pharmacological Data)

control: saline; PD: postnatal day; WAY-100635: N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride

Comment (Pharmacological Data)

No effect

Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 - 20 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in saline; injected once per day for 4 days

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Method (Pharmacological Data)

rats killed 1 week after treatment; brains removed, cortex homogenized; <3H>-paroxetine binding to cortical membrane preparation (SERT density) measured by liquid scintillation counting

Further Details (Pharmacological Data)

saline control; animals kept at 22 or 28 deg C for 6 h after title comp. administration; SERT: 5-HT transporter

Results

title comp. caused significant reduction (23 percent of vehicle treatment at 20 mg/kg) in <3H>-paroxetine binding (diagram)

Callaghan, Paul D.; Farrand, Kirsten; Salem, Abdallah; Hughes, Patrick; Daws, Lynette C.; Irvine, Rodney J.; European Journal of Pharmacology; vol. 546; nb. 1-3; (2006); p. 74 - 81, View in Reaxys 45 of 116

Effect (Pharmacological Data)

transmitter release; inhibition of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 - 20 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in saline; injected twice per day for 4 days

Method (Pharmacological Data)

rats killed 2 weeks after the final dose; brains removed, cortex homogenized; 5-HT, dopamine and their metabolites (5-HIAA, DOPAC) determined by HPLC-ED

Further Details (Pharmacological Data)

saline control; animals kept at 22 deg C

Results

title comp. significantly reduced cortical 5-HT content (at 10 and 20 mg/kg: 63 and 39 percent resp., cf. control), reduced 5-HIAA content (at 10 and 20 mg/kg: 68 and 51 percent resp., cf. control); no effect on cortical dopamine and DOPAC content (diagram)

Effect (Pharmacological Data)

transmitter release; inhibition of

Species or Test-System (Pharmacological Data)

Dark Agouti rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

12.5 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.9 percent w/v NaCl

Method (Pharmacological Data)

rats were injected with title comp. at 22 deg C; 1 - 32 weeks later concentrations of 5-HT or 5-HIAA in homogenate of cortex, hippocampus and striatum were assessed; HPLC

Further Details (Pharmacological Data)

saline control; 5-HT: 5-hydroxytryptamine; 5-HIAA: 5-hydroxyindoleacetic acid; 5-HT synthesis rate was calculated; further investigations using rats housed at 4 deg C for 4 h before and 6 h after treatment

Results

title comp. at 22 or 4 deg C stably reduced 5-HT content in cortex, hippocampus and caused transient (for 2 weeks) decrease of 5-HT content in striatum; 5-HT synthesis rate was constant; title comp. had similar effect on 5-HIAA content (figure)

O'Shea, Esther; Orio, Laura; Escobedo, Isabel; Sanchez, Veronica; Camarero, Jorge; Green, Alfred Richard; Colado, Maria Isabel; British Journal of Pharmacology; vol. 148; nb. 6; (2006); p. 778 - 785, View in Reaxys 47 of 116

Effect (Pharmacological Data)

receptor blocking agent

Species or Test-System (Pharmacological Data)

Dark Agouti rat

Sex

male

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Route of Application

intraperitoneal

Concentration (Pharmacological Data)

12.5 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.9 percent w/v NaCl

Method (Pharmacological Data)

rats were injected with title comp. at 22 deg C; 1 - 32 weeks later cortex, hippocampus and striatum were homogenized; incubation with <3H>-paroxetine (1 nmol/l) and 5-HT (100 μmol/l) for 90 min; binding of <3H>-paroxetine to 5-HT uptake sites

Further Details (Pharmacological Data)

saline control; 5-HT: 5-hydroxytryptamine; further investigations using rats housed at 4 deg C for 4 h before and 6 h after treatment

Results

title comp. decreased binding of <3H>-paroxetine to 5-HT uptake site; at 4 deg C effect of title comp. was smaller in cortex and hippocampus (figure)

Effect (Pharmacological Data)

enzyme; inhib. of

Species or Test-System (Pharmacological Data)

Dark Agouti rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

12.5 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.9 percent w/v NaCl

Method (Pharmacological Data)

rats were injected with title comp. at 22 deg C; 1 - 32 weeks later NSD-1015 (100 mg/kg, i.p.) was injected 30 min before killing; tryptophan hydroxylase activity was determined by accumulation of 5-HTP

Further Details (Pharmacological Data)

saline control; 5-HTP: 5-hydroxytryptophan; further investigations using rats housed at 4 deg C for 4 h before and 6 h after treatment

Results

title comp. reduced hydroxylase activity in cortex and hippocampus up to 8 weeks and only for 1 week in striatum; at 4 deg C effect of title comp. was smaller in cortex and hippocampus (table)

Effect (Pharmacological Data)

body temperature; effect on

Species or Test-System (Pharmacological Data)

Dark Agouti rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

12.5 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.9 percent w/v NaCl

Method (Pharmacological Data)

rats were maintained at 22 or 4 deg C before and 6 h after treatment with title comp.; rectal temperature was measured for 5 h

Results

title comp. at 22 deg C acutely increased rectal temperature; at 4 deg C title comp. produced initial hypothermia (for 60 min) followed by slight rise in temperature (at 180 - 300 min) (figure)

Effect (Pharmacological Data)

action potential; effect on

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Species or Test-System (Pharmacological Data)

sheep cardiac Purkinje fiber

Sex

male

Concentration (Pharmacological Data)

0.1 - 10 μmol/l

Kind of Dosing (Pharmacological Data)

formulated in DMSO; added cumulatively

Method (Pharmacological Data)

after 30 min. treatment with title comp. fibers placed to two-channel recording chamber with two silver stimulation electrodes; 1 Hz; square-wave constant voltage pulses ca. 0.05 ms; cardiac action potentials (AP) monitored

Further Details (Pharmacological Data)

analysed parameters: AP duration at 50 percent or 90 percent repolarisation, maximum rate of rise in AP upstroke, upstroke amplitude, diastolic membrane potential; further investigation with dl-sotalol, human ether-a-go-go related gene/K(1+) current blocker

Results

10 μmol/l of title comp. induced significant prolongation of AP duration at 90 percent repolarisation (figure, table)

Sheridan, Robert D.; Turner, Simon R.; Cooper, Graham J.; Tattersall, John E.H.; European Journal of Pharmacology; vol. 511; nb. 2-3; (2005); p. 99 - 107, View in Reaxys 51 of 116

Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

C57BL/6J mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

30 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in saline

Method (Pharmacological Data)

animals treated with title comp. three times at 3-h intervals; blood and striatum homogenate collected 60 min after last injection for measurement of metabolites using gas chromatography-mass spectrometry and HPLC

Further Details (Pharmacological Data)

control: vehicle; MDA: 3,4-methylenedioxyamphetamine; HMMA: 4-hydroxy-3-methoxymethamphetamine; HHMA: 3,4-dihydroxymethamphetamine; HMA: 4-hydroxy-3-methoxyamphetamine

Results

plasma levels of title comp. were 450 percent higher than MDA and 1900 percent higher than those of HMMA; levels of HHMA and HMA were similar and represented 1 and 5 percent of title comp. and MDA, resp.; in striatum only title comp. and MDA detected

Comment (Pharmacological Data)

Further metabolite(s)

Metabolite XRN (Pharmacological Data)

3251333; 3261956; 150196

Metabolite (Pharmacological Data)

(+/-)-DHMA; 4-Hydroxy-3-methoxymethamphetamine; 3,4-methylenedioxyamphetamine

Escobedo, Isabel; O'Shea, Esther; Orio, Laura; Sanchez, Veronica; Segura, Mireia; De La Torre, Rafael; Farre, Magi; Green, Alfred Richard; Colado, Maria Isabel; British Journal of Pharmacology; vol. 144; nb. 2; (2005); p. 231 - 241, View in Reaxys 52 of 116

Effect (Pharmacological Data)

transmitter release; inhibition of

Species or Test-System (Pharmacological Data)

C57BL/6J mouse

Sex

male

Route of Application

intracerebral

Concentration (Pharmacological Data)

1 - 100 μg

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Kind of Dosing (Pharmacological Data)

dissolved in phosphate buffer saline

Method (Pharmacological Data)

animals treated with title comp. into striatum three times at 3-h intervals and killed 1 h after last injection; striatum, hippocampus or cortex dissected and homogenised; changes in 5-HIAA, HVA, dopamine, 5-HT and DOPAC concentrations measured by HPLC

Further Details (Pharmacological Data)

control: vehicle; 5-HIAA: 5-hydroxyindolacetic acid; HVA: homovanillic acid; 5-HT: 5-hydroxytriptamine; DOPAC: 3.4-dihydroxyphenylacetic acid

Results

title comp. decreased DOPAC content (at 100 μg) in ipsilateral striatum (figure) but produced no change in either striatal dopamine or 5-HT content of striatum, hippocampus or cortex and brain concentration of 5-HIAA and HVA

Effect (Pharmacological Data)

transmitter release; inhibition of

Species or Test-System (Pharmacological Data)

C57BL/6J mouse

Sex

male

Route of Application

intracerebral

Concentration (Pharmacological Data)

1 - 100 μg

Kind of Dosing (Pharmacological Data)

dissolved in phosphate buffer saline

Method (Pharmacological Data)

animals treated with title comp. into striatum three times at 3-h intervals, killed 7 days after last injection; striatum, hippocampus or cortex dissected and homogenised; changes in 5HIAA, HVA, dopamine, 5-HT and DOPAC concentrations measured by HPLC

Further Details (Pharmacological Data)

control: vehicle; 5-HIAA: 5-hydroxyindolacetic acid; HVA: homovanillic acid; 5-HT: 5-hydroxytriptamine; DOPAC: 3.4-dihydroxyphenylacetic acid

Results

title comp. decreased dopamine content (at 100 μg) in ipsilateral striatum (figure) but produced no change in 5-HT content in striatum, hippocampus or cortex and in brain concentration of 5-HIAA, DOPAC and HVA

Effect (Pharmacological Data)

hyperthermic

Species or Test-System (Pharmacological Data)

C57BL/6J mouse

Sex

male

Route of Application

intracerebral

Concentration (Pharmacological Data)

1 - 100 μg

Kind of Dosing (Pharmacological Data)

dissolved in phosphate buffer saline

Method (Pharmacological Data)

animals treated with title comp. into striatum three times at 3-h intervals; changes in rectal temperature measured

Further Details (Pharmacological Data)

control: vehicle

Comment (Pharmacological Data)

No effect

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55 of 116

Effect (Pharmacological Data)

transmitter release; inhibition of

Species or Test-System (Pharmacological Data)

C57BL/6J mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

30 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in saline

Method (Pharmacological Data)

animals treated with title comp. three times at 3-h intervals and killed 1 h after last injection; striatum, hippocampus and cortex dissected out and homogenised; changes in dopamine, DOPAC, HVA, 5-HT and 5-HIAA concentrations measured by HPLC

Further Details (Pharmacological Data)

control: vehicle; DOPAC: 3,4-dihydroxyphenylacetic acid; HVA: homovanillic acid; 5-HT: 5hydroxytriptamine; 5-HIAA: 5-hydroxyindolacetic acid

Results

title comp. produced acute reduction of dopamine and DOPAC content and increase in HVA concentration in striatum; there was modest reduction in 5-HT levels in both hippocampus and cortex (figure), but 5-HIAA concentration was unaltered

Effect (Pharmacological Data)

transmitter release; inhibition of

Species or Test-System (Pharmacological Data)

C57BL/6J mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

30 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in saline

Method (Pharmacological Data)

animals treated with title comp. three times at 3-h intervals and killed 7 days after last injection; striatum, hippocampus and cortex dissected out and homogenised; changes in dopamine, DOPAC, HVA, 5-HT and 5-HIAA concentrations measured by HPLC

Further Details (Pharmacological Data)

control: vehicle; DOPAC: 3,4-dihydroxyphenylacetic acid; HVA: homovanillic acid; 5-HT: 5hydroxytriptamine; 5-HIAA: 5-hydroxyindolacetic acid

Results

title comp. produced long-term depletion of striatal concentration of dopamine, DOPAC and HVA; there was no change in 5-HT or 5-HIAA concentration in any of the areas studied

Effect (Pharmacological Data)

hyperthermic

Species or Test-System (Pharmacological Data)

C57BL/6J mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

30 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in saline

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Method (Pharmacological Data)

animals treated with title comp. three times at 3-h intervals; changes in rectal temperature measured

Further Details (Pharmacological Data)

control: vehicle

Results

title comp. produced modest hyperthermic response after first dose; effect was more pronounced after second and third injections (figure)

Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

7.5 mg/kg

Kind of Dosing (Pharmacological Data)

given every 2 h, three doses

Method (Pharmacological Data)

3 d or 2 wk after title comp. administration frontal cortex, caudate, and hippocampus dissected; cortical 5-HT measured by HPLC with electrochemical detection to choose typical samples for analysis of neurotoxic markers by Western blot

Further Details (Pharmacological Data)

control: saline; positive control: 5,7-dihydroxytryptamine (150 μg, i.c.v.); 5-HT: serotonin; markers included HSP32, peripheral benzodiazepine receptor, glial fibrillary acidic protein, 5-HT transporter, synapsin-1; HSP: heat shock protein

Results

title comp. increased only HSP-32 in cortex and caudate in 3 d postinjection animals by ca. 30 percent indicating no significant evidence of neurotoxicity

Wang, Xiaoying; Baumann, Michael H.; Xu, Heng; Morales, Marisela; Rothman, Richard B.; Journal of Pharmacology and Experimental Therapeutics; vol. 314; nb. 3; (2005); p. 1002 - 1012, View in Reaxys 59 of 116

Effect (Pharmacological Data)

transporter translocation; induction of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

7.5 mg/kg

Kind of Dosing (Pharmacological Data)

given every 2 h, three doses

Method (Pharmacological Data)

2 wk after title comp. treatment frontal cortex, caudate, and hippocampus dissected, homogenized, centrifuged; fractions enreached with plasma membranes or endosomes separated; checked by special markers; SERT 50- and 70-kDa detected by Western blotting

Further Details (Pharmacological Data)

control: saline; SERT: serotonin transporter; markers for plasma membranes and endosomes were Na/K-ATPase and EEA1, resp.

Comment (Pharmacological Data)

No effect

Effect (Pharmacological Data)

transporter binding; inhibition of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

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Route of Application

intraperitoneal

Concentration (Pharmacological Data)

7.5 mg/kg

Kind of Dosing (Pharmacological Data)

given every 2 h, three doses

Method (Pharmacological Data)

2 wk after title comp. treatment brain removed; membranes prepared from whole brain minus caudate; SERT binding sites labeled with <125I>RTI-55; HEPES buffer, pH 7.4; incubation time 2 h at 25 deg C

Further Details (Pharmacological Data)

control: saline; SERT: serotonin transporter; <125I>RTI-55: 3β(4'-125iodophenyl)tropan-2β-carboxylic acid methyl ester

Results

title comp. decreased SERT binding by 82 percent

Effect (Pharmacological Data)

transmitter depletion; induction of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

7.5 mg/kg

Kind of Dosing (Pharmacological Data)

given every 2 h, three doses

Method (Pharmacological Data)

3 d or 2 wk after title comp. administration frontal cortex dissected and homogenized; 5HT measured by high-pressure liquid chromatography with electrochemical detection; percentage of depletion calculated

Further Details (Pharmacological Data)

control: saline; positive control: 5,7-DHT (150 μg, i.c.v. single dose); 5-HT: serotonin; 5,7DHT: dihydroxytryptamine

Results

percentage of depletion in 3-d post title comp. injection group was 64.6, in 2-wk postinjection group 68.4

Effect (Pharmacological Data)

pyrogenic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

7.5 mg/kg

Kind of Dosing (Pharmacological Data)

given every 2 h, three doses

Method (Pharmacological Data)

colonic temperature measured immidiately after each injection of title comp.

Further Details (Pharmacological Data)

control: saline

Results

mean colonic temperature after third injection of title comp. was 39.6 deg C compared to 36.9 deg C in control

Effect (Pharmacological Data)

pharmacokinetics

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Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

female

Route of Application

peroral

Concentration (Pharmacological Data)

5 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. was diluted in water

Method (Pharmacological Data)

adolescent normal and prenatally stressed rats (30 days of age) treated with title comp.; trunk blood collected at 15, 60, 120 and 180 min; title comp. conc. measured by headspace solid-phase microextraction tandem gas chromatography-mass spectrometry

Further Details (Pharmacological Data)

prenatal stress induced by 45-min exposition of pregnant rats to bright light three times a day from day 11 to day 21

Results

title comp. showed reduced elimination rates in prenatally stressed rats

Morley-Fletcher, Sara; Puopolo, Maria; Gentili, Stefano; Gerra, Gilberto; Macchia, Teodora; Laviola, Giovanni; European Journal of Pharmacology; vol. 489; nb. 1-2; (2004); p. 89 - 92, View in Reaxys 64 of 116

Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

female

Route of Application

peroral

Concentration (Pharmacological Data)

5 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. was diluted in water

Method (Pharmacological Data)

adolescent normal and prenatally stressed rats (30 days of age) trained to MCT and then treated with title comp.; 15, 60, 120 and 180 min later rats tested; episodes of impaired balance (inactivity, frequency of slips and of twists) recorded

Further Details (Pharmacological Data)

prenatal stress induced by 45-min exposition of pregnant rats three times a day to bright light from day 11 to 21; MCT: motor coordination test (rats trained to traverse straight Plexiglas runway suspended 1 m above the floor)

Results

title comp. increased motor alterations in prenatally stressed rats

Effect (Pharmacological Data)

nephrotoxic

Species or Test-System (Pharmacological Data)

Wistar rat renal proximal tubular cells

Sex

male

Concentration (Pharmacological Data)

100 - 800 μmol/l

Method (Pharmacological Data)

cells isolated from renal cortex tissue by collagenase enzymatic digestion, filtration and density centrifugation; cell monolayer incub. for 24 h with title comp.; cell viability determ. by MTT assay

Further Details (Pharmacological Data)

cell viability >85 percent; rats maintain. on 12 h day/night; MTT=3-(4,5-dimethyl-1,3-thiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide; in MTT assay cells incubated at 37 deg C in humid. atmosphere cont. 5 percent CO2 for 4 h with MTT, absorbance measur. at 540 nm

Comment (Pharmacological Data)

No effect

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Carvalho, Marcia; Hawksworth, Gabrielle; Milhazes, Nuno; Borges, Fernanda; Monks, Terrence J.; Fernandes, Eduarda; Carvalho, Felix; Bastos, Maria; Archives of Toxicology; vol. 76; nb. 10; (2002); p. 581 - 588, View in Reaxys 66 of 116

Effect (Pharmacological Data)

nephrotoxic

Species or Test-System (Pharmacological Data)

human renal proximal tubular cells

Concentration (Pharmacological Data)

100 - 800 μmol/l

Method (Pharmacological Data)

cells isolated from renal cortex tissue by collagenase enzymatic digestion, filtration and density centrifugation; cell monolayer incub. for 24 h with title comp.; cell viability determ. by MTT assay

Further Details (Pharmacological Data)

cell viability > 85 percent; MTT=3-(4,5-dimethyl-1,3-thiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide; in MTT assay cells incubated at 37 deg C in humidified atmosphere cont. 5 percent CO2 for 4 h with MTT, then absorbance measured at 540 nm

Comment (Pharmacological Data)

No effect

Effect (Pharmacological Data)

uptake; inhibition of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

four injections with 2-h intervals

Method (Pharmacological Data)

rats received title comp. at 24 or 6 deg C; after 1 or 24 h, killed; striatal synaptosomes or vesicles prepared; incubated with <3H>DA; filtered through Whatman GF/B filters; radioactivity counted using liquid scintillation counter

Further Details (Pharmacological Data)

DA: dopamine; further investigation in presence of tyrosine hydroxylase inhibitor α-methylp-tyrosine hydrochloride (αMT, for plasmalemmal uptake) or D2 receptor antagonist eticlopride (for vesicular uptake)

Results

title comp. sign. decreased plasmalemmal <3H>DA uptake at 1 h at 24 or 6 deg C; no effect at 24 h; effect was not altered by αMT; sign. decreased vesicular <3H>DA uptake at 1 h at 24 or 6 deg C; less effective at 24 h; effect inhibited by eticlopride

Paul Hansen; Riddle, Evan L.; Sandoval, Veronica; Brown, Jeffrey M.; Gibb, James W.; Hanson, Glen R.; Fleckenstein, Annette E.; Journal of Pharmacology and Experimental Therapeutics; vol. 300; nb. 3; (2002); p. 1093 - 1100, View in Reaxys 68 of 116

Effect (Pharmacological Data)

uptake; inhibition of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat striatal synaptosomes

Sex

male

Concentration (Pharmacological Data)

10 μmol/l

Method (Pharmacological Data)

synaptosomes incubated with title comp. for 30 min at 37 deg C; incubated with <3H>dopamine at 37 deg C for 3 min; filtered through Whatman GF/B filters; radioactivity counted using liquid scintillation counter

Further Details (Pharmacological Data)

further investigation in presence of protein kinase C inhibitors NPC15437 and Ro31-7549

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Results

title comp. sign. decreased plasmalemmal <3H>dopamine uptake; effect was attenuated by NPC15437 and Ro31-7549 (figure)

Effect (Pharmacological Data)

pyrogenic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

four injections with 2-h intervals

Method (Pharmacological Data)

rats received title comp. at 24 or 6 deg C; core (rectal) body temperature recorded using digital thermometer

Results

title comp. increased core body temperature by ca. 2 - 4 deg C (figure)

Effect (Pharmacological Data)

binding; inhibition of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

four injections with 2-h intervals

Method (Pharmacological Data)

rats received title comp. at 24 deg C; at 1 or 24 h decapitated; striatal synaptosomes prepared; incubated with <3H>WIN35428 for 2 h on ice, pH 7.4; filtered through Whatman GF/B filters; radioactivity counted using liquid scintillation counter

Further Details (Pharmacological Data)

further investigation in presence of tyrosine hydroxylase inhibitor α-methyl-p-tyrosine hydrochloride (αMT)

Results

title comp. sign. reduced <3H>WIN35428 binding at both 1 and 24 h after treatment; effect was not altered by αMT (figures)

Effect (Pharmacological Data)

binding; inhibition of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

four injections with 2-h intervals

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Method (Pharmacological Data)

rats received title comp. at 24 deg C; at 1 or 24 h decapitated; striatal vesicles prepared; incubated with <3H>DHTBZ for 10 min at 25 deg C; filtered through Whatman GF/B filters; radioactivity counted using liquid scintillation counter

Further Details (Pharmacological Data)

DHTBZ: dihydrotetrabenazine, vesicular monoamine transporter-2 ligand

Results

title comp. sign. reduced <3H>DHTBZ binding at both 1 and 24 h after treatment (figure)

Effect (Pharmacological Data)

binding; inhibition of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat striatal tissue

Concentration (Pharmacological Data)

10 μmol/l

Method (Pharmacological Data)

striatal tissue incubated with title comp. for 30 min at 37 deg C; at 1 or 24 h synaptosomes prepared; incubated with <3H>WIN35428 for 2 h on ice, pH 7.4; filtered through Whatman GF/B filters; radioactivity counted using liquid scintillation counter

Comment (Pharmacological Data)

No effect

Effect (Pharmacological Data)

brain glycogen levels; decrease of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

40 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. was dissolved in 0.15 mol/l NaCl

Method (Pharmacological Data)

rats were administered with title comp.; 0.5 to 4 h post-dosing, sacrificed; brain removed; glycogen concentration determined

Further Details (Pharmacological Data)

control: vehicle

Results

title comp. caused time-dependent reduction of glycogen concentration; glycogen content was reduced by 45percent; significant reduction in concentration of glycogen observed 30 min and 1 h post-dosing; diagram

Darvesh, Altaf S.; Shankaran, Mahalakshmi; Gudelsky, Gary A.; Journal of Pharmacology and Experimental Therapeutics; vol. 301; nb. 1; (2002); p. 138 - 144, View in Reaxys 74 of 116

Effect (Pharmacological Data)

brain glycogen levels; decrease of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 - 40 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. was dissolved in 0.15 mol/l NaCl

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Method (Pharmacological Data)

rats were administered with title comp.; 1 h post-dosing, sacrificed; brains removed; glycogen concentration determined

Further Details (Pharmacological Data)

control: vehicle; further study: effect of desipramine, iprindole and LY-53,857 on title comp. effect

Results

title comp. caused dose-dependent decrease in glycogen concentration; magnitude of effect was greatest at 40 mg/kg; desipramine, iprindole and LY-53,857 caused signif. attenuation of title comp.-induced reduction in brain conc. of glycogen; diagrams

Darvesh, Altaf S.; Shankaran, Mahalakshmi; Gudelsky, Gary A.; Journal of Pharmacology and Experimental Therapeutics; vol. 301; nb. 1; (2002); p. 138 - 144, View in Reaxys 75 of 116

Effect (Pharmacological Data)

brain glycogen levels; decrease of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. was dissolved in 0.15 mol/l NaCl

Method (Pharmacological Data)

rats were maintained at an ambient temperature of 24 or 17 deg C; 2 h later, administered with title comp.; 1 h post-dosing, sacrificed; brains removed; glycogen concentration determined

Further Details (Pharmacological Data)

control: vehicle

Results

title comp. caused 25-30percent reduction in brain concentration of glycogen in rats maintained at 24 deg C and title comp. had no effect on brain glycogen concentration in rats maintained at 17 deg C; diagram

Darvesh, Altaf S.; Shankaran, Mahalakshmi; Gudelsky, Gary A.; Journal of Pharmacology and Experimental Therapeutics; vol. 301; nb. 1; (2002); p. 138 - 144, View in Reaxys 76 of 116

Effect (Pharmacological Data)

hyperthermic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 - 20 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. was dissolved in 0.15 mol/l NaCl

Method (Pharmacological Data)

rats maintained at an ambient temperature of 24 or 17 deg C for 2 h prior to or following admin. of title comp.; body temperature recorded at 30 min intervals for 90 min pre- and 1.5 h post-dosing using telethermometer and thermister probe

Further Details (Pharmacological Data)

control: vehicle; further study with LY-53,857

Results

title comp. at an ambient temperature of 24 deg C, increased body temperature by 1.1 and 1.4 deg C at 10 and 20 mg/kg, resp.; maintenance of rats at 17 deg C or treatment with LY-53,857 completely prevented title comp.-induced hyperthermia; table

Darvesh, Altaf S.; Shankaran, Mahalakshmi; Gudelsky, Gary A.; Journal of Pharmacology and Experimental Therapeutics; vol. 301; nb. 1; (2002); p. 138 - 144, View in Reaxys 77 of 116

Effect (Pharmacological Data)

brain glucose levels; increase of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

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Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 - 40 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. was dissolved in 0.15 mol/l NaCl

Method (Pharmacological Data)

rats were implanted with dialysis probe into the striatum; administered with title comp.; dialysis samples collected every 30 min; glucose concentration determined

Further Details (Pharmacological Data)

control: vehicle; further study: LY-53,857 effect on title comp.

Results

title comp. caused immediate and sustained increase of 30-45percent in extracellular glucose conc. in striatum which remained elevated for at least 5 h post-dosing; LY-53,857 attenuated title comp.-induced increase in extracellular conc. of glucose; diagrams

Darvesh, Altaf S.; Shankaran, Mahalakshmi; Gudelsky, Gary A.; Journal of Pharmacology and Experimental Therapeutics; vol. 301; nb. 1; (2002); p. 138 - 144, View in Reaxys 78 of 116

Effect (Pharmacological Data)

hepatotoxic

Species or Test-System (Pharmacological Data)

Charles-River mouse hepatocytes

Concentration (Pharmacological Data)

100 - 1600 μmol/l

Method (Pharmacological Data)

in vitro; hepatocytes in Krebs-Henseleit buffer preincub. for 30 min at 37 deg C; incub. with title comp. at 37-41 deg C for 3 h; cell viability determ. by trypan blue exclusion and LDH leakage; GSH and GSSG levels determ.; lipid peroxidation also

Further Details (Pharmacological Data)

hepatocytes obtained from mice weighing 24-30 g; GSH = glutathione; lipid peroxidation meas. by thiobarbituric acid reactive substances assay

Results

dose- and time-dependent GSH depletion at 37 deg C; negligible effect on lipid peroxidation or cell viability at 37 deg C; GSH depletion, lipid peroxidation and loss of cell viability (up to 90-100 percent) at 41 deg C

Carvalho, Marcia; Carvalho, Felix; Bastos, Maria Lourdes; Archives of Toxicology; vol. 74; nb. 12; (2001); p. 789 - 793, View in Reaxys 79 of 116

Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

human

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

47.6 mg

Kind of Dosing (Pharmacological Data)

equiv. 40 mg free base; in capsule form with ca. 200 ml of water

Method (Pharmacological Data)

8 healthy volunteers, 22-32 years; blood samples collected from forearm vein at 0.5, 1, 2, 4, 6, 8 and 24 h after title comp. administration; plasma separated; GC-MS

Results

title comp. conc. in plasma were 45.2 μg/l at 2 h, reaching maximum of 47.0 μg/l at 4 h after administration; graphic representation

Forsling; Fallon; Kicman; Hutt; Cowan; Henry; Journal of Pharmacy and Pharmacology; vol. 53; nb. 10; (2001); p. 1357 - 1363, View in Reaxys 80 of 116

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

human

Sex

male

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Route of Application

peroral

Concentration (Pharmacological Data)

47.6 mg

Kind of Dosing (Pharmacological Data)

equiv. 40 mg free base; in capsule form with ca. 200 ml of water

Method (Pharmacological Data)

8 healthy volunteers, 22-32 years; blood samples collected from forearm vein at 0.5, 1, 2, 4, 6, 8 and 24 h after title comp. administration; plasma separated; GC-MS

Further Details (Pharmacological Data)

(R)-MDA and (S)-MDA: N-demethylated metabolites of title comp.

Results

plasma conc. of (S)-MDA exceeded conc. of (R)-MDA in all volunteers up to 8 h after title comp. administration; mean Cmax of (S)-MDA and (R)-MDA: 2.9 and 1.0 μg/l, resp.

Metabolite XRN (Pharmacological Data)

5260331; 5260330

Metabolite (Pharmacological Data)

(-)-Tenamfetamine; (+)-Tenamfetamine

Forsling; Fallon; Kicman; Hutt; Cowan; Henry; Journal of Pharmacy and Pharmacology; vol. 53; nb. 10; (2001); p. 1357 - 1363, View in Reaxys 81 of 116

Effect (Pharmacological Data)

toxicokinetics

Species or Test-System (Pharmacological Data)

human

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

47.6 mg

Kind of Dosing (Pharmacological Data)

equiv. 40 mg free base; in capsule form with ca. 200 ml of water

Method (Pharmacological Data)

8 healthy volunteers, 22-32 yrs; blood samples collected from forearm vein up to 24 h after title comp.; pulse rate, blood pressure monitored; plasma conc. of AVP and cortisol determined by radioummunoassay; sodium conc. and osmolality determined; GC-MS

Further Details (Pharmacological Data)

AVP: arginine vasopressin; (R)-MDA and (S)-MDA: N-demethylated metabolites of title comp.

Results

plasma AVP increased between 1 and 4 h after title comp. administration; signif. negative correlation observed between AVP conc. and single and total enantiomer title comp. at 1 h; no correlation between AVP conc. and metabolites conc. at 1-2 h; graphs

Metabolite XRN (Pharmacological Data)

5260331; 5260330

Metabolite (Pharmacological Data)

(-)-Tenamfetamine; (+)-Tenamfetamine

Forsling; Fallon; Kicman; Hutt; Cowan; Henry; Journal of Pharmacy and Pharmacology; vol. 53; nb. 10; (2001); p. 1357 - 1363, View in Reaxys 82 of 116

Effect (Pharmacological Data)

toxicokinetics

Species or Test-System (Pharmacological Data)

human

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

47.6 mg

Kind of Dosing (Pharmacological Data)

equiv. 40 mg free base; in capsule form with ca. 200 ml of water

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Method (Pharmacological Data)

Results

no signif. change was observed for osmolality or cortisol at 1 h after title comp. ingestion; sodium conc. signif. decreased at 0.5-2 h; at 24 h, osmolality and sodium conc. were signif. above basal values and no marked increase in cortisol; graphs

Metabolite XRN (Pharmacological Data)

5260331; 5260330

Metabolite (Pharmacological Data)

(-)-Tenamfetamine; (+)-Tenamfetamine

Forsling; Fallon; Kicman; Hutt; Cowan; Henry; Journal of Pharmacy and Pharmacology; vol. 53; nb. 10; (2001); p. 1357 - 1363, View in Reaxys 83 of 116

Effect (Pharmacological Data)

pyrogenic

Species or Test-System (Pharmacological Data)

NIH/Swiss mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

25 mg/kg

Kind of Dosing (Pharmacological Data)

given in saline (0.9 percent NaCl), in volume of 10 ml/kg

Method (Pharmacological Data)

rectal temperature measured after treatment

Results

first title comp. dose produced rapid rise in rectal temperature lasting over 2 h, second and third doses given at 3 and 6 h after first dose also rapidly increased temperature

Colado; Camarero; Mechan; Sanchez; Esteban; Elliott; Green; British Journal of Pharmacology; vol. 134; nb. 8; (2001); p. 1711 - 1723, View in Reaxys 84 of 116

Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

NIH/Swiss mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

25 mg/kg

Kind of Dosing (Pharmacological Data)

given in saline (0.9 percent NaCl), in volume of 10 ml/kg; total of 3 doses given at 3 h intervals

Method (Pharmacological Data)

7 days after title comp. treatment, mice killed; cerebral dopamine (and HVA and DOPAC) and 5-HT (and 5-HIAA) content measured by HPLC with amperometric detection

Further Details (Pharmacological Data)

HVA: homovanillic acid; DOPAC: 3,4-dihydroxyphenylacetic acid; 5-HT: 5-hydroxytryptamine; further studies on free radical production

Results

two title comp. doses produced 57 percent decrease in striatal dopamine concentration, 3 doses had 71 percent decline; HVA and DOPAC decreased in similar way; free radical production increased

Colado; Camarero; Mechan; Sanchez; Esteban; Elliott; Green; British Journal of Pharmacology; vol. 134; nb. 8; (2001); p. 1711 - 1723, View in Reaxys 85 of 116

Effect (Pharmacological Data)

hyperthermic

Species or Test-System (Pharmacological Data)

albino Wistar rat

Sex

male

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Route of Application

intraperitoneal

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.9percent saline and administered at high dose (5 mg/kg over 4 h) or moderate dose (5 mg/kg for first hour followed by vehicle for 3 h) for 2 consecutive days

Method (Pharmacological Data)

rats administered with title comp.; body temperature measured

Further Details (Pharmacological Data)

controls: vehicle, amphetamine

Results

signif. increase in core body temperature for 2, 3, 4 hous observed in high dose title comp.-treated rats on day 1 and day 2 relative to moderate regimen and control groups; fig.

Morley, Kirsten C; Gallate, Jason E; Hunt, Glenn E; Mallet, Paul E; McGregor, Iain S; European Journal of Pharmacology; vol. 433; nb. 1; (2001); p. 91 - 99, View in Reaxys 86 of 116

Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

albino Wistar rat

Sex

male

Route of Application

intraperitoneal

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.9percent saline and administered at high dose (5 mg/kg over 4 h) or moderate dose (5 mg/kg for first hour followed by vehicle for 3 h) for 2 consecutive days

Method (Pharmacological Data)

rats administered with title comp.; placed in standard operant chambers floor of which consisted of 16 metal bars; single count occurred when rat changed its position on any one bar relative to others; counts recorded; locomotor activity measured

Further Details (Pharmacological Data)

controls: vehicle, amphetamine

Results

high dose title comp. group displayed signif. higher locomotor activity than vehicle for hour 3 and 4 on day 1 and displayed signif. higher locomotor activity than vehicle and moderate dose title comp.-treated group for hour 3 and 4 on day 2; fig.

Morley, Kirsten C; Gallate, Jason E; Hunt, Glenn E; Mallet, Paul E; McGregor, Iain S; European Journal of Pharmacology; vol. 433; nb. 1; (2001); p. 91 - 99, View in Reaxys 87 of 116

Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

albino Wistar rat

Sex

male

Route of Application

intraperitoneal

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.9percent saline and administered at high dose (5 mg/kg over 4 h) or moderate dose (5 mg/kg for first hour followed by vehicle for 3 h) for 2 consecutive days

Method (Pharmacological Data)

rats admin. with title comp.; 12 weeks later, placed in hide box of emergence apparatus; emergence latency, emergence frequency, duration of time spent on open field, risk assessment, no. of rears tested scored for 5 min

Further Details (Pharmacological Data)

controls: vehicle, amphetamine

Results

high dose regimen treated group had longer emergency latency, less open field time and less rear time than controls; both high and moderated dose title comp.-treated groups showed signif. less emergence frequency than vehicle; table

Morley, Kirsten C; Gallate, Jason E; Hunt, Glenn E; Mallet, Paul E; McGregor, Iain S; European Journal of Pharmacology; vol. 433; nb. 1; (2001); p. 91 - 99, View in Reaxys 88 of 116

Effect (Pharmacological Data)

behavioural symptoms

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Species or Test-System (Pharmacological Data)

albino Wistar rat

Sex

male

Route of Application

intraperitoneal

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.9percent saline and administered at high dose (5 mg/kg over 4 h) or moderate dose (5 mg/kg for first hour followed by vehicle for 3 h) for 2 consecutive days

Method (Pharmacological Data)

rats admin. with title comp.; 12 weeks later, placed in centre part of elevated plus maze with their head facing closed arm; open and closed arm times and number of open and closed entries recorded for 5min

Further Details (Pharmacological Data)

controls: vehicle, amphetamine

Results

high and moderate dose title comp.-treated groups showed decreased time in open arms and no. of open arms entries and displayed signif. increase in amount of time spent in closed arms compared to control; table

Morley, Kirsten C; Gallate, Jason E; Hunt, Glenn E; Mallet, Paul E; McGregor, Iain S; European Journal of Pharmacology; vol. 433; nb. 1; (2001); p. 91 - 99, View in Reaxys 89 of 116

Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

albino Wistar rat

Sex

male

Route of Application

intraperitoneal

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.9percent saline and administered at high dose (5 mg/kg over 4 h) or moderate dose (5 mg/kg for first hour followed by vehicle for 3 h) for 2 consecutive days

Method (Pharmacological Data)

rats administered with title comp.; 12 weeks later, placed in social interaction test arena (square clear Perspex box dimly lit with red light for 10 min); interactions of rats were recorded; aggressive type of behaviour also recorded

Further Details (Pharmacological Data)

controls: vehicle, amphetamine

Results

high dose title comp.-treated rats showed decrease in total duration of interaction time, no. of interactions, no. of rears and squares crossed; high and moderate dose treated rats showed signif. decrease in social interaction relative control; table

Morley, Kirsten C; Gallate, Jason E; Hunt, Glenn E; Mallet, Paul E; McGregor, Iain S; European Journal of Pharmacology; vol. 433; nb. 1; (2001); p. 91 - 99, View in Reaxys 90 of 116

Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

albino Wistar rat

Sex

male

Route of Application

intraperitoneal

Kind of Dosing (Pharmacological Data)

title comp. dissolved in 0.9percent saline and administered at high dose (5 mg/kg over 4 h) or moderate dose (5 mg/kg for first hour followed by vehicle for 3 h) for 2 consecutive days

Method (Pharmacological Data)

rats received title comp.; 14 weeks later, exposed to 2 identical objects in memory testing arena for 10 min; after delay (15 or 60 min with 7 days between each test), rats placed back in arena for 10 min with one object replaced by new one and obsd.

Further Details (Pharmacological Data)

controls: vehicle, amphetamine; object recognition test measures non-spatial working memory in rat

Results

high dose title comp. treated-group displayed signif. less percentage time investigating novel object than controls; no signif. group differences in overall investigation time for both 60- and 15- min delays; table

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Morley, Kirsten C; Gallate, Jason E; Hunt, Glenn E; Mallet, Paul E; McGregor, Iain S; European Journal of Pharmacology; vol. 433; nb. 1; (2001); p. 91 - 99, View in Reaxys 91 of 116

Effect (Pharmacological Data)

drug interaction

Species or Test-System (Pharmacological Data)

Fawn-Hooded rats

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

0.15 mg/kg

Method (Pharmacological Data)

in vivo; rats trained to discriminate title comp. (1.5 mg/kg); LSD (0.04 mg/kg) and title comp. injected; number of responses and needed time on title comp. or saline lever analysed

Further Details (Pharmacological Data)

experiment was terminated after accumulation of 10 responses on one of two levers; control, saline-treated trained rats

Results

rats tested with title comp. produced a saline-like response; co-administration of title comp. and LSD synergized to produce maximal title comp.-like effect; required time to reach 10 responses increased by approximately 522 percent compared to control

Schechter, Martin D.; European Journal of Pharmacology; vol. 341; nb. 2-3; (1998); p. 131 - 134, View in Reaxys 92 of 116

Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

female

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. admin. every other day from embryonic day 6 to 20

Method (Pharmacological Data)

pregnant rats admin. with title comp.; rat pups killed at postnatal day 15; brains removed; concentration of 5-HT, 5-HIAA, dopamine, DOPAC and HVA detd. by HPLC

Further Details (Pharmacological Data)

control: saline; 5-HT: 5-hydroxytryptamine; HIAA: hydroxyindoleacetic acid; HVA: homovanillic acid; DOPAC: dihydroxyphenylacetic acid

Results

title comp. had no effect on postnatal levels of 5-HT, 5-HIAA, dopamine, DOPAC and HVA; table

Aguirre; Barrionuevo; Lasheras; Del Rio; Journal of Pharmacology and Experimental Therapeutics; vol. 286; nb. 3; (1998); p. 1159 - 1165, View in Reaxys 93 of 116

Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

female

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. admin. every other day from embryonic day 6 to 20

Method (Pharmacological Data)

pregnant rats admin. with title comp.; rat pups killed at postnatal day 15; brains removed; homogenized; incubated (10 min, 37 deg C); incubation mixture containing <3H>P added; incubated (60 min, 22 deg C); binding to 5-HT transporter determined

Further Details (Pharmacological Data)

control: saline; <3H>P: <3H>paroxetine; 5-HT: 5-hydroxytrptamine

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Results

title comp. did not cause any significant change in density of 5-HT transporters

Aguirre; Barrionuevo; Lasheras; Del Rio; Journal of Pharmacology and Experimental Therapeutics; vol. 286; nb. 3; (1998); p. 1159 - 1165, View in Reaxys 94 of 116

Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Wistar rat pup

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Method (Pharmacological Data)

pups at different PND14, 21, 28 and 35 admin. with title comp.; killed after 7 d; brains removed; homogenized; incubated, 10 min, 37 deg C; incubation mixture containing <3H>P added; incubated (60 min, 22 deg C); binding to 5-HT transporter determined

Further Details (Pharmacological Data)

control: saline; <3H>P: <3H>paroxetine; PND: postnatal days; 5-HT: 5-hydroxytryptamine

Results

title comp. did not cause significant change in density of 5-HT transporters at PND28; at PND35, 5-HT transporter density significantly decreased in frontal cortex

Aguirre; Barrionuevo; Lasheras; Del Rio; Journal of Pharmacology and Experimental Therapeutics; vol. 286; nb. 3; (1998); p. 1159 - 1165, View in Reaxys 95 of 116

Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Wistar rat pup

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Method (Pharmacological Data)

pups (21 d) in groups admin. with/without L-DOPA (15 min before)/R-DOI; title comp. admin.; killed after 7 d; brains removed; homogenized; incubation mixture contg. <3H>P added; incubated (60 min, 22 deg C); binding to 5-HT transporter detd.

Further Details (Pharmacological Data)

control: saline; <3H>P: <3H>paroxetine; L-DOPA (L-3,4-dihydroxyphenylalanine), 80 mg/kg, s.c.; R-DOI ((R)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane), 0.5 mg/kg, s.c.; FC: frontal cortex; HC: hippocampus; 5-HT: 5-hydroxytryptamine

Results

title comp. + R-DOI did not alter 5-HT transporter level/change <3H>P-labeled 5-HT uptake sites; title comp. + L-DOPA caused significant long term reduction of 5-HT, decreased density of sites in FC/HC, not significant in striatum/hypothalamus; diagrams

Aguirre; Barrionuevo; Lasheras; Del Rio; Journal of Pharmacology and Experimental Therapeutics; vol. 286; nb. 3; (1998); p. 1159 - 1165, View in Reaxys 96 of 116

Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Method (Pharmacological Data)

rats (ca. 3-mo) admin. DP; 6-HD admin. after 1 h; after 8 d, admin. with title comp., with/ without L-DOPA; killed after 7 d; brains removed; homogenized; IM contg. <3H>P added; incubated (60 min, 22 deg C); binding to 5-HTT (5-HT transporter) determined

Further Details (Pharmacological Data)

controls: sham, saline; <3H>P: <3H>paroxetine; IM: incubation mixture; FC: frontal cortex; HC: hippocampus; 5-HT: 5-hydroxytryptamine; DP: desipramine-HCl (25 mg/kg, i.p.); 6HD: 6-hydroxydopamine-HBr (100 μg/ml); L-DOPA: L-3,4-dihydroxyphenylalanine

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Results

title comp. did not produce any change in conc. of 5-HT levels/5-HTT density in 6-HD lesioned rats; title comp. + L-DOPA caused 40-60 percent reduction of 5-HT in FC, HC, striatum, hypothalamus; signif. decreased 5-HTT density by 40 and 50 percent in FC and HC, resp.

Aguirre; Barrionuevo; Lasheras; Del Rio; Journal of Pharmacology and Experimental Therapeutics; vol. 286; nb. 3; (1998); p. 1159 - 1165, View in Reaxys 97 of 116

Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Method (Pharmacological Data)

rats (postnatal day 21) admin. with/without L-DOPA (15 min before, 80 mg/kg, s.c.)/R-DOI (0.5 mg/kg, s.c.); title comp. admin.; rectal temp. recorded every 30 min up to 240 min with a lubricated digital thermometer probe

Further Details (Pharmacological Data)

control: saline; sensitivity of immature rats to title comp. induced hyperthermia develops concomitantly with sensitivity to long-term neurotoxicity; L-DOPA: L-3,4-dihydroxyphenylalanine; R-DOI: (R)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane

Results

title comp. signif. raised temp. lasted ca. 4 h; returned to control after 240 min; highest raise (ca. 2 deg C) observed after 90 min; title comp. + L-DOPA/R-DOI signif. raised temp.; highest raise (ca. 3/2.5 deg C, resp.) after 90 min observed; diagram

Aguirre; Barrionuevo; Lasheras; Del Rio; Journal of Pharmacology and Experimental Therapeutics; vol. 286; nb. 3; (1998); p. 1159 - 1165, View in Reaxys 98 of 116

Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Method (Pharmacological Data)

pups at different postnatal days (PND) 14, 21, 28, 35 admin. with title comp.; killed after 7 days; brains removed; concentrations of 5-HT, 5-HIAA, dopamine, DOPAC and HVA determined by HPLC

Further Details (Pharmacological Data)

control: saline; FC: frontal cortex; HT: hydroxytrptamine; HIAA; hydroxyindoleacetic acid; DOPAC: dihydroxyphenylacetic acid; HVA: homovanillic acid

Results

title comp. (PND14/21) caused no signif. reduction of 5-HT/dopamine/DOPAC/HVA; at PND28, signif. reduced 5-HT conc. in hippocampus but not in FC/striatum/hypothalamus and signif. long-term reduction obsd. at PND35; 5-HIAA conc. paralleled to 5-HT; table

Aguirre; Barrionuevo; Lasheras; Del Rio; Journal of Pharmacology and Experimental Therapeutics; vol. 286; nb. 3; (1998); p. 1159 - 1165, View in Reaxys 99 of 116

Effect (Pharmacological Data)

enzyme; inhib. of

Species or Test-System (Pharmacological Data)

human liver microsomes

Method (Pharmacological Data)

effect on activity of enzyme CYP2D6 studied; 0.5 to 5.0 μmol/l dextromethorphan incubated in 0.2 mol/l phosphate buffer with (μmol/l): 0.1 NADP, 1 glucose-6-phosphate, 0.5 MgCl2 and 0.2 U glucose-6-phosphate dehydrogenase with/without title compound

Further Details (Pharmacological Data)

reaction started by adding microsomal protein; incubation at 37 deg C for 30 min; stopped with 70 percent perchloric acid; centrifuged; supernatant assayed for dextrorphan by HPLC

Results

competitive inhibitory effect; apparent inhibition constant (Ki) = 0.6 μmol/l

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Wu, Dafang; Victoria Otton, S.; Inaba, Tadanobu; Kalow, Werner; Sellers, Edward M.; Biochemical Pharmacology; vol. 53; nb. 11; (1997); p. 1605 - 1612, View in Reaxys 100 of 116

Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Dark Agouti rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

15 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.9 percent w/v NaCl

Method (Pharmacological Data)

rats weighing 150-170 g housed at 21 deg C and 12 h light/dark cycle with free access to food, water; <3H>-paroxetine binding in hippocampus, cortex after 7 d administration; incubation for 60 min at r.t.; ANOVA

Results

app. 65 percent loss of binding in cerebral tissue

Colado; O'Shea; Granados; Murray; Green; British Journal of Pharmacology; vol. 121; nb. 5; (1997); p. 889 - 900, View in Reaxys 101 of 116

Effect (Pharmacological Data)

hyperthermic

Species or Test-System (Pharmacological Data)

Dark Agouti rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

10 - 15 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.9 percent w/v NaCl

Method (Pharmacological Data)

rats weighing 150-170 g housed at 21 deg C and 12 h light/dark cycle with free access to food, water; rectal temperature; ANOVA

Results

10 mg/kg (n=6) produced modest elevation of temperature, 15 mg/kg (n=10) produced marked increase

Colado; O'Shea; Granados; Murray; Green; British Journal of Pharmacology; vol. 121; nb. 5; (1997); p. 889 - 900, View in Reaxys 102 of 116

Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Dark Agouti rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

10 - 15 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.9 percent w/v NaCl

Method (Pharmacological Data)

rats weighing 150-170 g housed at 21 deg C and 12 h light/dark cycle with free access to food, water; effect on monoamines and their metabolites conc. in brain regions 7 d after administration

Further Details (Pharmacological Data)

HPLC; ANOVA

Results

conc. of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid was reduced by over 50 percent in hippocampus, cortex, striatum, no change in conc. of dopamine or 3,4-dihydroxyphenylacetic acid in striatum

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Colado; O'Shea; Granados; Murray; Green; British Journal of Pharmacology; vol. 121; nb. 5; (1997); p. 889 - 900, View in Reaxys 103 of 116

Effect (Pharmacological Data)

free radical formation; induction of

Species or Test-System (Pharmacological Data)

Dark Agouti rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

10 - 15 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in 0.9 percent w/v NaCl

Method (Pharmacological Data)

rats weighing 150-170 g housed at 21 deg C and 12 h light/dark cycle with free access to food, water; radical formation assessed by formation of 2,3- and 2,5-dihydroxybenzoic acid (2,3-DHBA, 2,5-DHBA) from salicylic acid

Further Details (Pharmacological Data)

probe implantation into hippocampus; in vivo microdialysis; HPLC; electrochemical detection; ANOVA

Results

at 15 mg/kg dose increased formation of 2,3-DHBA (but not 2,5-DHBA) for at least 6 h

Colado; O'Shea; Granados; Murray; Green; British Journal of Pharmacology; vol. 121; nb. 5; (1997); p. 889 - 900, View in Reaxys 104 of 116

Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

female

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

twice daily dose for 4 d in saline

Method (Pharmacological Data)

250 g pregnant rats (T=21 deg C; 12 h light/dark cycle); start of treatment on day 14 of gestation; on day 7 postpartum dams and pups sacrificed; cortex, hippocampus, striatum (dams); dorsal telencephalon (pups) isolated

Further Details (Pharmacological Data)

homogenized tissues analysed for 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid (5-HIAA), dopamine (DOP) by HPLC

Results

in dams, 7 days postpartum: 5-HT, 5-HIAA decreased by over 65 percent (hippocampus, striatum), by 45 percent (cortex); in contrast, 5-HT, 5-HIAA in the dorsal telencephalon of the pups was unaffected; DOP unaffected in all tissues (diagram)

Colado; O'Shea; Granados; Misra; Murray; Green; British Journal of Pharmacology; vol. 121; nb. 4; (1997); p. 827 - 833, View in Reaxys 105 of 116

Effect (Pharmacological Data)

lipid peroxidation; stimulation of

Species or Test-System (Pharmacological Data)

rat

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

40 mg/kg

Kind of Dosing (Pharmacological Data)

single dose

Method (Pharmacological Data)

title comp. inj. to 160-180 g adult rats and to neonate pups (7-10 days, 15-20 g); 3 or 6 h postinjection sacrificed; cortex, hippocampus isolated from adult, forebrain with hippocampus from neonate rats

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Further Details (Pharmacological Data)

homogenized tissues analysed for thiobarbituric acid reactive substances (TBARS) using the 2-thiobarbituric acid color reaction; effect on TBARS as measure of lipid peroxidation studied

Results

in adult rats 94/41 percent increase of TBARS (3/6 h) in cortex, 16 percent (insignificant) increase in hippocampus (3 h) measd.; in neonate cortex no change in TBARS at either 3 or 6 h postinjection; diagrams

Colado; O'Shea; Granados; Misra; Murray; Green; British Journal of Pharmacology; vol. 121; nb. 4; (1997); p. 827 - 833, View in Reaxys 106 of 116

Effect (Pharmacological Data)

toxicity

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

female

Route of Application

subcutaneous

Concentration (Pharmacological Data)

20 mg/kg

Kind of Dosing (Pharmacological Data)

twice daily dose for 4 d in saline

Method (Pharmacological Data)

250 g pregnant rats (T=21 deg C; 12 h light/dark cycle) treated with title comp. on days 14-17 of gestation; measured: body weight, rectal temperature of dams during treatment; litter size, body weight of pups

Results

body weight of dams decreased during treatment (graph), marked hyperthermia observed after 1-st dose; modest (20 percent) decrease in litter size, no significant decrease in the weight of pups (graph)

Colado; O'Shea; Granados; Misra; Murray; Green; British Journal of Pharmacology; vol. 121; nb. 4; (1997); p. 827 - 833, View in Reaxys 107 of 116

Effect (Pharmacological Data)

training drug

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

0.25 - 1.5 mg/kg

Method (Pharmacological Data)

title compound administered 15 min before various concentrations i.p. injection of 6,7(methylenedioxy)-2-aminotetralin HCl and its N-methyl derivative; 6,7,8,9-tetrahydro-1,3dioxolo<4,5-h>isoquinoline HCl and its 7-methyl derivative

Further Details (Pharmacological Data)

5,6,7,8-tetrahydro-1,3-dioxolo<4,5-g>isoquinoline and its 7-methyl derivative; 5,6-methylenedioxy-2-aminoindan and its N-methyl derivative; 4,5-methylenedioxy-2-aminoindan and its N-methyl derivative; stimulus generalization recorded during 2.5 min

Type (Pharmacological Data)

ED50

Value of Type (Pharmacological Data)

0.57 mg/g

Results

tetrahydroisoquinoline derivatives did not result in stimulus generalization; 6,7-(methylenedioxy)-2-aminotetralin produced 83 percent, 5,6-methylenedioxy-2-aminoindan and its Nmethyl derivative produced 92 and 83 percent drug-appropriate responding, resp.

Effect (Pharmacological Data)

receptor; binding activity

Species or Test-System (Pharmacological Data)

human 5-HT2A receptors

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Method (Pharmacological Data)

cells grown, harvested and competition assays performed using <3H>DOB radioligand

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

870 nmol/l

Results

increased affinity for <3H>DOB labeled receptors

Effect (Pharmacological Data)

receptor; binding activity

Species or Test-System (Pharmacological Data)

human 5-HT2A receptors

Method (Pharmacological Data)

cells grown, harvested and competition assays performed using <3H>ketanserin radioligand

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

1200 nmol/l

Results

modest affinity for <3H>ketanserin labeled receptors

Effect (Pharmacological Data)

central stimulation

Species or Test-System (Pharmacological Data)

albino ICR mice

Sex

male and female

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

1 - 30 mg/kg

Kind of Dosing (Pharmacological Data)

1, 3, 10, and 30 mg/kg

Exposure Period (Pharmacological Data)

10 - 40 min

Method (Pharmacological Data)

mouse weight 25-30 g; acclimated for 30 min prior to drug treament; central stimulation assayed by locomotor activity (distance traversed) and by rearing frequency, recorded simultaneously by computerized video tracking and behavior recognition system

Results

significantly increased both locomotor activity and rearing frequency

Effect (Pharmacological Data)

dopamine efflux

Species or Test-System (Pharmacological Data)

Sprague-Dawley rats

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

10 - 20 mg/kg

Exposure Period (Pharmacological Data)

240 - 300 min

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Method (Pharmacological Data)

rats (295-325 g) anesthetized, cannulated (anterolateral striatum, substantia nigra, cortex); title compd. applied, dialysate (in vivo microdialysis) sampled, anal. (HPLC, electrochem. detection)

Results

time-dependent dopamine extracellular concn. in striatum and substantia nigra evaluated (diagrams)

Yamamoto; Nash; Gudelsky; Journal of Pharmacology and Experimental Therapeutics; vol. 273; nb. 3; (1995); p. 1063 - 1070, View in Reaxys 112 of 116

Effect (Pharmacological Data)

serotonin efflux

Species or Test-System (Pharmacological Data)

Sprague-Dawley rats

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

20 mg/kg

Exposure Period (Pharmacological Data)

240 min

Method (Pharmacological Data)

rats (295-325 g) anesthetized, cannulated (anterolateral striatum, substantia nigra, cortex); title compd. applied, dialysate (in vivo microdialysis) sampled, anal. (HPLC, electrochem. detection)

Results

time-dependent serotonin extracellular concn. in substantia nigra evaluated (diagrams)

Yamamoto; Nash; Gudelsky; Journal of Pharmacology and Experimental Therapeutics; vol. 273; nb. 3; (1995); p. 1063 - 1070, View in Reaxys 113 of 116

Effect (Pharmacological Data)

γ-aminobutyric acid efflux

Species or Test-System (Pharmacological Data)

Sprague-Dawley rats

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

20 mg/kg

Exposure Period (Pharmacological Data)

240 min

Method (Pharmacological Data)

rats (295-325 g) anesthetized, cannulated (anterolateral striatum, substantia nigra, cortex); title compd. applied, dialysate (in vivo microdialysis) sampled, anal. (HPLC, electrochem. detection)

Results

time-dependent γ-butyric acid extracellular concn. in substantia nigra evaluated (diagrams)

Yamamoto; Nash; Gudelsky; Journal of Pharmacology and Experimental Therapeutics; vol. 273; nb. 3; (1995); p. 1063 - 1070, View in Reaxys 114 of 116

Effect (Pharmacological Data)

thermoregulatoric

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

20 - 40 mg/kg

Method (Pharmacological Data)

newborn rats used (22 deg C; R.H.= 50 percent; 12 h light:drak cycle); treated at different age (postnatal day 10, PND10, PND40, PND70) and diff. ambient temp. (10, 25, 33 deg C); rectal temperatures (bT) measured every hour for 10 h (starting: treatment)

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Further Details (Pharmacological Data)

title comp. effect on body temp. studied

Results

PND10: slight hyperthermic effect (T+) (10 deg C); slight hypothermic effect (T-) (25 deg C); at 33 deg C bT unaffected; PND40, PND70: T- (10 deg C); T+ (>=25 deg C) (graph, table)

Broening; Bowyer; Slikker Jr.; Journal of Pharmacology and Experimental Therapeutics; vol. 275; nb. 1; (1995); p. 325 - 333, View in Reaxys 115 of 116

Effect (Pharmacological Data)

neuroregulatoric

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

20 - 40 mg/kg

Method (Pharmacological Data)

newborn rats used (22 deg C; R.H.= 50 percent; 12 h light:drak cycle); treated at different age (postnatal day 10, PND10, PND40, PND70) and diff. ambient temp. (10, 25, 33 deg C); 1 w after title comp. sacrificed; brains removed; frontal corex (FC) dissected

Further Details (Pharmacological Data)

hippocampus (H), striatum (S) also studied; 5-HT content in brain tissues determined by HPLC; 5-HT reuptake sites (5-HT-re) by <3H>paroxetin binding; title comp. effect on 5-HT, 5-HT-re studied

Results

PND10: 5-HT- 5-HT-re unaffected; PND40, PND70: 5-HT, 5-HT-re unaffected (10 deg C), significantly reduced (25-33 deg C)

Broening; Bowyer; Slikker Jr.; Journal of Pharmacology and Experimental Therapeutics; vol. 275; nb. 1; (1995); p. 325 - 333, View in Reaxys 116 of 116

Comment (Pharmacological Data)

psychotropic activity in male Sprague-Dawley rats

Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015, View in Reaxys

Reaxys ID 6577933 View in Reaxys

H N

32/52 Chemical Name: MDMA hydrochloride; (S)-(+)-N-methyl-1(1,3-benzodioxol-5-yl)-2-propanamine hydrochloride; (S)-1(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine hydrochloride; 3,4-methylenedioxymethamphetamine hydrochloride; (S)-3,4-methylenedioxymethamphetamine; (+)-3,4-methylenedioxymethamphetamine hydrochloride; (+)-MDMA Linear Structure Formula: C11H15NO2*ClH Molecular Formula: C11H15NO2*ClH Molecular Weight: 229.707 Type of Substance: heterocyclic InChI Key: LUWHVONVCYWRMZ-QRPNPIFTSA-N Note:

H O O

Substance Label (4) Label References HCl (S)-10a

(S)-7e*HCl

Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374, View in Reaxys

MDMA

Farfel; Seiden; Journal of Pharmacology and Experimental Therapeutics; vol. 272; nb. 2; (1995); p. 860 867, View in Reaxys

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S-2a*HCl

Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015, View in Reaxys

Patent-Specific Data (1) References Patent; Caron, Marc G.; Sotnikova, Tatyana D.; Gainetdinov, Raul R.; US2007/27208; (2007); (A1) English, View in Reaxys Melting Point (2) 1 of 2

Melting Point [°C]

187

Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374, View in Reaxys 2 of 2

Melting Point [°C]

192 - 193

Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015, View in Reaxys Optical Rotatory Power (2) 1 of 2

Type (Optical Rotatory Power)

[alpha]

Concentration (Optical Rotatory Power)

1.00 g/100ml

Solvent (Optical Rotatory Power)

H2O

Optical Rotatory Power [deg]

17.9

Wavelength (Optical Ro- 589 tatory Power) [nm] Temperature (Optical Rotatory Power) [°C]

Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374, View in Reaxys 2 of 2

Type (Optical Rotatory Power)

[alpha]

Concentration (Optical Rotatory Power)

1 g/100ml

Solvent (Optical Rotatory Power)

H2O

Optical Rotatory Power [deg]

17.43

Wavelength (Optical Ro- 589 tatory Power) [nm] Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015, View in Reaxys NMR Spectroscopy (2) 1 of 2

Description (NMR Spec- Chemical shifts troscopy) Nucleus (NMR Spectroscopy)

Solvents (NMR Spectro- CDCl3 scopy) Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374, View in Reaxys 2 of 2

Description (NMR Spec- Spin-spin coupling constants troscopy) Solvents (NMR Spectro- CDCl3 scopy)

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Comment (NMR Spectroscopy)

1H-1H

Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374, View in Reaxys Pharmacological Data (40) 1 of 40

Comment (Pharmacological Data)

Bioactivities present

Patent; Caron, Marc G.; Sotnikova, Tatyana D.; Gainetdinov, Raul R.; US2007/27208; (2007); (A1) English, View in Reaxys; Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015, View in Reaxys; Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374, View in Reaxys; Farfel; Seiden; Journal of Pharmacology and Experimental Therapeutics; vol. 272; nb. 2; (1995); p. 860 - 867, View in Reaxys; McClung, Jessica; Fantegrossi, William; Howell, Leonard L.; Psychopharmacology; vol. 210; nb. 1; (2010); p. 75 - 83, View in Reaxys; Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys; Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46, View in Reaxys 2 of 40

Effect (Pharmacological Data)

transmitter uptake; inhibition of

Species or Test-System (Pharmacological Data)

hippocampal synaptosomes of Sprague-Dawley rat

Sex

male

Further Details (Pharmacological Data)

5-HT: serotonin; competitive inhibition using 15 nM [3H]5-HT; inhibitory concentration (IC); IC50 related to: 5-HT

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

4.13 μmol/l

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 3 of 40

Effect (Pharmacological Data)

transmitter uptake; inhibition of

Species or Test-System (Pharmacological Data)

hippocampal synaptosomes of Sprague-Dawley rat

Sex

male

Further Details (Pharmacological Data)

5-HT: serotonin; competitive inhibition using 15 nM [3H]5-HT

Results

molecular target: rat serotonin transporter

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 4 of 40

Effect (Pharmacological Data)

transmitter uptake; inhibition of

Species or Test-System (Pharmacological Data)

hippocampal synaptosomes of Sprague-Dawley rat

Sex

male

Concentration (Pharmacological Data)

300 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. preincubated for 1 h

Further Details (Pharmacological Data)

5-HT: serotonin; persistent inhibition studied using 15 nM [3H]5-HT; inhibition rate related to: 5-HT

Type (Pharmacological Data)

inhibition rate

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Value of Type (Pharmacological Data)

100 - 48.4 percent

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 5 of 40

Effect (Pharmacological Data)

transmitter uptake; inhibition of

Species or Test-System (Pharmacological Data)

hippocampal synaptosomes of Sprague-Dawley rat

Sex

male

Concentration (Pharmacological Data)

300 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. preincubated for 1 h

Further Details (Pharmacological Data)

5-HT: serotonin; persistent inhibition studied using 15 nM [3H]5-HT

Results

molecular target: rat serotonin transporter

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 6 of 40

Effect (Pharmacological Data)

transmitter uptake; inhibition of

Species or Test-System (Pharmacological Data)

striatal synaptosomes of Sprague-Dawley rat

Sex

male

Further Details (Pharmacological Data)

competitive inhibition using 5 nM [3H]DA; DA: dopamine; inhibitory concentration (IC); IC50 related to: dopamine

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

3.9 μmol/l

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 7 of 40

Effect (Pharmacological Data)

transmitter uptake; inhibition of

Species or Test-System (Pharmacological Data)

striatal synaptosomes of Sprague-Dawley rat

Sex

male

Further Details (Pharmacological Data)

competitive inhibition using 5 nM [3H]DA; DA: dopamine

Results

molecular target: rat dopamine transporter

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 8 of 40

Effect (Pharmacological Data)

transmitter uptake; inhibition of

Species or Test-System (Pharmacological Data)

striatal synaptosomes of Sprague-Dawley rat

Sex

male

Concentration (Pharmacological Data)

5 - 300 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. preincubated for 1 h

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Further Details (Pharmacological Data)

persistent inhibition studied using 5 nM [3H]dopamine; inhibition rate related to: dopamine

Type (Pharmacological Data)

inhibition rate

Value of Type (Pharmacological Data)

30 percent

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 9 of 40

Effect (Pharmacological Data)

transmitter uptake; inhibition of

Species or Test-System (Pharmacological Data)

striatal synaptosomes of Sprague-Dawley rat

Sex

male

Concentration (Pharmacological Data)

5 - 300 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. preincubated for 1 h

Further Details (Pharmacological Data)

persistent inhibition studied using 5 nM [3H]dopamine

Results

molecular target: rat dopamine transporter

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 10 of 40

Effect (Pharmacological Data)

transmitter uptake; inhibition of

Species or Test-System (Pharmacological Data)

striatal synaptosomes of Sprague-Dawley rat

Sex

male

Further Details (Pharmacological Data)

reserpine-treated (endogenous dopamine depleted) rats used ; persistent inhibition studied using [3H]dopamine

Results

no effect (related to dopamine)

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 11 of 40

Effect (Pharmacological Data)

binding affinity

Species or Test-System (Pharmacological Data)

cortical membranes of Sprague-Dawley rat

Sex

male

Further Details (Pharmacological Data)

radioligand displacement assay using 0.05 nM [3H]paroxetine; inhibitory concentration (IC); IC50 related to: serotonin transporter

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

20.5 μmol/l

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 12 of 40

Effect (Pharmacological Data)

binding affinity

Species or Test-System (Pharmacological Data)

cortical membranes of Sprague-Dawley rat

Sex

male

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Further Details (Pharmacological Data)

radioligand displacement assay using 0.05 nM [3H]paroxetine; inhibition constant (Ki); Ki related to: serotonin transporter

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

3.1 μmol/l

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 13 of 40

Effect (Pharmacological Data)

binding affinity

Species or Test-System (Pharmacological Data)

cortical membranes of Sprague-Dawley rat

Sex

male

Further Details (Pharmacological Data)

radioligand displacement assay using 0.05 nM [3H]paroxetine

Results

molecular target: rat serotonin transporter

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 14 of 40

Effect (Pharmacological Data)

binding affinity

Species or Test-System (Pharmacological Data)

striatal membranes of Sprague-Dawley rat

Sex

male

Further Details (Pharmacological Data)

radioligand displacement assay using 5 nM [3H]WIN35428; inhibitory concentration (IC); IC50 related to: dopamine transporter

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

27.09 μmol/l

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 15 of 40

Effect (Pharmacological Data)

binding affinity

Species or Test-System (Pharmacological Data)

striatal membranes of Sprague-Dawley rat

Sex

male

Further Details (Pharmacological Data)

radioligand displacement assay using 5 nM [3H]WIN35428; inhibition constant (Ki); Ki related to: dopamine transporter

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

14.78 μmol/l

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 16 of 40

Effect (Pharmacological Data)

binding affinity

Species or Test-System (Pharmacological Data)

striatal membranes of Sprague-Dawley rat

Sex

male

Further Details (Pharmacological Data)

radioligand displacement assay using 5 nM [3H]WIN35428

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Results

molecular target: rat dopamine transporter

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 17 of 40

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

cow brain mitochondria suspension

Further Details (Pharmacological Data)

MAOB: monoamine oxidase B; substrate: benzylamine (0.01 mM); inhibitory concentration (IC); IC50 related to: MAOB

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

1 mmol/l

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 18 of 40

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

cow brain mitochondria suspension

Further Details (Pharmacological Data)

MAOB: monoamine oxidase B; substrate: benzylamine (0.01 mM); inhibition constant (Ki); Ki related to: MAOB

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

81.8 μmol/l

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 19 of 40

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

cow brain mitochondria suspension

Further Details (Pharmacological Data)

MAOB: monoamine oxidase B; substrate: benzylamine (0.01 mM)

Results

molecular target: bovine MAOB

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 20 of 40

Effect (Pharmacological Data)

cell viability; inhibition of

Species or Test-System (Pharmacological Data)

PC 12 cells

Further Details (Pharmacological Data)

non-differentiated cells used; WST-8 assay; inhibitory concentration (IC)

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

2.45 mmol/l

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 21 of 40

Effect (Pharmacological Data)

apoptosis; induction of

Species or Test-System (Pharmacological Data)

PC 12 cells

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Further Details (Pharmacological Data)

tilte comp produced 58percent of died cells (killed by apoptosis) at 4mM; flow cytometry; inhibitory concentration (IC)

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

3.67 mmol/l

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 22 of 40

Effect (Pharmacological Data)

receptor binding affinity

Species or Test-System (Pharmacological Data)

brain membranes of Sprague-Dawley rat

Sex

male

Further Details (Pharmacological Data)

radioligand displacement assay using 2 nM [3H]MLA; inhibitory concentration (IC); IC50 related to: nicotinic acetylcholine receptor subtype α7

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

71.34 μmol/l

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 23 of 40

Effect (Pharmacological Data)

receptor binding affinity

Species or Test-System (Pharmacological Data)

brain membranes of Sprague-Dawley rat

Sex

male

Further Details (Pharmacological Data)

radioligand displacement assay using 2 nM [3H]MLA; inhibition constant (Ki); Ki related to: nicotinic acetylcholine receptor subtype α7

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

27.3 μmol/l

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 24 of 40

Effect (Pharmacological Data)

receptor binding affinity

Species or Test-System (Pharmacological Data)

brain membranes of Sprague-Dawley rat

Sex

male

Further Details (Pharmacological Data)

radioligand displacement assay using 2 nM [3H]MLA

Results

molecular target: rat nicotinic acetylcholine receptor subtype α7

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 25 of 40

Effect (Pharmacological Data)

receptor binding affinity

Species or Test-System (Pharmacological Data)

brain membranes of Sprague-Dawley rat

Sex

male

Further Details (Pharmacological Data)

radioligand displacement assay using 1 nM [3H]Epibatidine; inhibitory concentration (IC); IC50 related to: nicotinic acetylcholine receptor subtype α4β2

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Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

52.46 μmol/l

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 26 of 40

Effect (Pharmacological Data)

receptor binding affinity

Species or Test-System (Pharmacological Data)

brain membranes of Sprague-Dawley rat

Sex

male

Further Details (Pharmacological Data)

radioligand displacement assay using 1 nM [3H]Epibatidine; inhibition constant (Ki); Ki related to: nicotinic acetylcholine receptor subtype α4β2

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

2.5 μmol/l

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 27 of 40

Effect (Pharmacological Data)

receptor binding affinity

Species or Test-System (Pharmacological Data)

brain membranes of Sprague-Dawley rat

Sex

male

Further Details (Pharmacological Data)

radioligand displacement assay using 1 nM [3H]Epibatidine

Results

molecular target: rat nicotinic acetylcholine receptor subtype α4β2

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 28 of 40

Effect (Pharmacological Data)

transmitter uptake; inhibition of

Species or Test-System (Pharmacological Data)

striatal synaptosomes of Sprague-Dawley rat

Sex

male

Further Details (Pharmacological Data)

control: 100 percent; inhibition rate related to: dopamine

Type (Pharmacological Data)

inhibition rate

Value of Type (Pharmacological Data)

76.23 percent

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 29 of 40

Effect (Pharmacological Data)

transmitter uptake; inhibition of

Species or Test-System (Pharmacological Data)

striatal synaptosomes of Sprague-Dawley rat

Sex

male

Further Details (Pharmacological Data)

control: 100 percent

Results

molecular target: rat dopamine

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Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 30 of 40

Effect (Pharmacological Data)

transmitter uptake; inhibition of

Species or Test-System (Pharmacological Data)

striatal synaptosomes of Sprague-Dawley rat

Sex

male

Kind of Dosing (Pharmacological Data)

title comp. incubated along with 7-NI (20 μmol/l)

Further Details (Pharmacological Data)

control: 100 percent; 7-NI: neuronal nitric oxide synthase inhibitor; inhibition rate related to: dopamine

Type (Pharmacological Data)

inhibition rate

Value of Type (Pharmacological Data)

76.71 percent

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 31 of 40

Effect (Pharmacological Data)

transmitter uptake; inhibition of

Species or Test-System (Pharmacological Data)

striatal synaptosomes of Sprague-Dawley rat

Sex

male

Kind of Dosing (Pharmacological Data)

title comp. incubated along with 7-NI (20 μmol/l)

Further Details (Pharmacological Data)

control: 100 percent; 7-NI: neuronal nitric oxide synthase inhibitor

Results

molecular target: rat dopamine

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 32 of 40

Effect (Pharmacological Data)

transmitter uptake; inhibition of

Species or Test-System (Pharmacological Data)

striatal synaptosomes of Sprague-Dawley rat

Sex

male

Kind of Dosing (Pharmacological Data)

title comp. incubated along with GF-109203X (0.25 μmol/l)

Further Details (Pharmacological Data)

control: 100 percent; GF-109203X : protein kinase C inhibitor; inhibition rate related to: dopamine

Type (Pharmacological Data)

inhibition rate

Value of Type (Pharmacological Data)

72.87 percent

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 33 of 40

Effect (Pharmacological Data)

transmitter uptake; inhibition of

Species or Test-System (Pharmacological Data)

striatal synaptosomes of Sprague-Dawley rat

Sex

male

Kind of Dosing (Pharmacological Data)

title comp. incubated along with GF-109203X (0.25 μmol/l)

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Further Details (Pharmacological Data)

control: 100 percent; GF-109203X : protein kinase C inhibitor

Results

molecular target: rat dopamine

Escubedo; Abad; Torres; Camarasa; Pubill; Neurochemistry International; vol. 58; nb. 1; (2011); p. 92 - 101, View in Reaxys 34 of 40

Effect (Pharmacological Data)

reinstate response to amphetamine self-administration; induction of

Species or Test-System (Pharmacological Data)

Macaca mulatta, rhesus monkey

Sex

male and female

Route of Application

intravenous

Concentration (Pharmacological Data)

0.3 - 0.1 mg/kg

Further Details (Pharmacological Data)

peak response rates induced by an amphetamine prime = 0.34 responses/s; mass of species: 8 - 15 kg

Type (Pharmacological Data)

peak response rate

Value of Type (Pharmacological Data)

51 percent

McClung, Jessica; Fantegrossi, William; Howell, Leonard L.; Psychopharmacology; vol. 210; nb. 1; (2010); p. 75 - 83, View in Reaxys 35 of 40

Effect (Pharmacological Data)

locomotor behaviors; effect on

Species or Test-System (Pharmacological Data)

DAT-KO mouse

Sex

male and female

Route of Application

intraperitoneal

Method (Pharmacological Data)

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were monitored for up to 3 h. In cumulative dosing experiments, animals were treated with increasing doses of drugs after a 1-h interval. For the akinesia test, the mouse is held by the tail so that it is standing on forelimbs only and moving on its own. The number of steps taken with both forelimbs was recorded during a 30-s trial [57]. The presence of catalepsy was determined and measured by placing the animal's forepaws on a horizontal wooden bar (0.7 cm in diameter), 4 cm above the tabletop. The time until the mouse removed both forepaws from the bar was recorded, with a maximum cut-off time of 3 min [53]. In the grasping test of muscular rigidity, the mouse is suspended by its forelimbs on a metal rod (diameter: 0.25 cm) positioned approximately 20 cm above the table. The time the animal remains on the rod (maximum 1 min) was noted [58]. To assess rigidity in a bracing task, the number of steps taken with each forelimb when the mouse is pushed sideways over a distance of 50 cm was recorded [57]. Tremor was scored visually in mice using the rating scale [54]: 0, no tremor; 1, occasional isolated twi Results

Akinesia test: ~6-70 number of steps; at Catalepsy test: ~49-170sec; at Grasping test: ~3-40 seconds time spent on the rod of the title compound administered after 2h of αMT treatment; title compound at high doses was able to induce significant forward locomotion; pretreatment with SCH23390 + raclopride did not affect locomotor action of the title compound; at 100 mg/kg of the title compound fails to affect DA dynamics in the striatum; figure is given

Location

Page/Page column 3-4; 12-15; sheet 9-10

Patent; Caron, Marc G.; Sotnikova, Tatyana D.; Gainetdinov, Raul R.; US2007/27208; (2007); (A1) English, View in Reaxys 36 of 40

Effect (Pharmacological Data)

hypothermic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

40 mg/kg

Kind of Dosing (Pharmacological Data)

single dose

Method (Pharmacological Data)

in vivo; effect on body temp. assayed; rats weighed 225-250 g; kept in individual cages at 20-22 deg C under 12 h light/dark cycle with free access to food and water; rats implanted with temp.-sensitive radiotransmitter into abdominal cavity

Further Details (Pharmacological Data)

body temp. measured for 4 h after treatment

Comment (Pharmacological Data)

No effect

Farfel; Seiden; Journal of Pharmacology and Experimental Therapeutics; vol. 272; nb. 2; (1995); p. 860 - 867, View in Reaxys 37 of 40

Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

40 mg/kg

Kind of Dosing (Pharmacological Data)

single dose

Method (Pharmacological Data)

in vivo; effect on brain 5-HT and 5-HIAA level assayed; rats weighed 225-250 g; kept in individual cages at 20-22 deg C under 12 h light/dark cycle with free access to food and water; rats killed 72 h after treatment; brain removed

Further Details (Pharmacological Data)

striatum and hippocampus dissected; 5-HT and 5-HIAA levels in striatum and hippocampus measured by HPLC; 5-HT: serotonin; 5-HIAA: 5-hydroxyindole acetic acid

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Results

title comp. decreased 5-HT/5-HIAA levels to 63/65 percent and to 58/61 percent in hippocampus and striatum, respectively

Farfel; Seiden; Journal of Pharmacology and Experimental Therapeutics; vol. 272; nb. 2; (1995); p. 860 - 867, View in Reaxys 38 of 40

Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Long-Evans rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

40 mg/kg

Kind of Dosing (Pharmacological Data)

single dose

Method (Pharmacological Data)

in vivo; effect on brain 5-HT and 5-HIAA level assayed; rats weighed 200-225 g; kept in individual cages at 20-22 deg C under 12 h light/dark cycle with free access to food and water; rats killed 72 h after treatment; brain removed

Further Details (Pharmacological Data)

striatum and hippocampus dissected; 5-HT and 5-HIAA levels in striatum and hippocampus measured by HPLC; 5-HT: serotonin; 5-HIAA: 5-hydroxyindole acetic acid

Results

title comp. decreased brain 5-HT and 5-HIAA levels

Farfel; Seiden; Journal of Pharmacology and Experimental Therapeutics; vol. 272; nb. 2; (1995); p. 860 - 867, View in Reaxys 39 of 40

Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

40 mg/kg

Kind of Dosing (Pharmacological Data)

single dose

Method (Pharmacological Data)

in vivo; effect on brain 5-HT and 5-HIAA level assayed; rats kept in individual cages at 23.5-26.5 deg C (rat body temp. was 38.4-40.4 deg C) under 12 h light/dark cycle with free access to food and water; rats killed 72 h after treatment; brain removed

Further Details (Pharmacological Data)

striatum and hippocampus dissected; 5-HT and 5-HIAA levels in striatum and hippocampus measured by HPLC; 5-HT: serotonin; 5-HIAA: 5-hydroxyindole acetic acid

Results

title comp. decreased 5-HT levels to 60 percent and 44 percent in hippocampus and striatum, respectively; title comp. decreased also 5-HIAA levels in hippocampus but not in striatum

Farfel; Seiden; Journal of Pharmacology and Experimental Therapeutics; vol. 272; nb. 2; (1995); p. 860 - 867, View in Reaxys 40 of 40

Comment (Pharmacological Data)

psychotropic activity in male Sprague-Dawley rats

Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015, View in Reaxys

Reaxys ID 6577934 View in Reaxys

33/52

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H N

Chemical Name: (R)-(-)-N-methyl-1-(1,3-benzodioxol-5-yl)-2propanamine hydrochloride; (R)-1-(benzo[d][1,3]dioxol-5-yl)-Nmethylpropan-2-amine hydrochloride; (R)-3,4-methylenedioxymethamphetamine Linear Structure Formula: C11H15NO2*ClH Molecular Formula: C11H15NO2*ClH Molecular Weight: 229.707 Type of Substance: heterocyclic InChI Key: LUWHVONVCYWRMZ-DDWIOCJRSA-N Note:

H O O

Substance Label (2) Label References HCl (R)-10a

R-2a*HCl

Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015, View in Reaxys

Melting Point (1) 1 of 1

Melting Point [°C]

192 - 193

Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015, View in Reaxys Optical Rotatory Power (1) 1 of 1

Type (Optical Rotatory Power)

[alpha]

Concentration (Optical Rotatory Power)

1 g/100ml

Solvent (Optical Rotatory Power)

H2O

Optical Rotatory Power [deg]

-17.54

Description (NMR Spec- Chemical shifts troscopy) Nucleus (NMR Spectroscopy)

Solvents (NMR Spectro- CDCl3 scopy) Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015, View in Reaxys 2 of 2

Description (NMR Spec- Spin-spin coupling constants troscopy) Solvents (NMR Spectro- CDCl3 scopy) Comment (NMR Spectroscopy)

1H-1H

Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015, View in Reaxys Pharmacological Data (3) 1 of 3

Comment (Pharmacological Data)

Bioactivities present

Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015, View in Reaxys; McClung, Jessica; Fantegrossi, William; Howell, Leonard L.; Psychopharmacolo-

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gy; vol. 210; nb. 1; (2010); p. 75 - 83, View in Reaxys; Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46, View in Reaxys 2 of 3

Effect (Pharmacological Data)

reinstate response to amphetamine self-administration; induction of

Species or Test-System (Pharmacological Data)

Macaca mulatta, rhesus monkey

Sex

male and female

Route of Application

intravenous

Concentration (Pharmacological Data)

0.3 mg/kg

Further Details (Pharmacological Data)

peak response rates induced by an amphetamine prime = 0.17 responses/s; mass of species: 8 - 15 kg

Type (Pharmacological Data)

peak response rate

Value of Type (Pharmacological Data)

29 percent

McClung, Jessica; Fantegrossi, William; Howell, Leonard L.; Psychopharmacology; vol. 210; nb. 1; (2010); p. 75 - 83, View in Reaxys 3 of 3

Comment (Pharmacological Data)

psychotropic activity in male Sprague-Dawley rats and in humans

Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015, View in Reaxys

Reaxys ID 10389717 View in Reaxys

H N

34/52 Chemical Name: (+)-ecstasy hydrochloride; (+)-MDMA hydrochloride; (+)-3,4-methylenedioxymethamphetamine hydrochloride Linear Structure Formula: C11H15NO2*ClH Molecular Formula: C11H15NO2*ClH Molecular Weight: 229.707 Type of Substance: heterocyclic InChI Key: LUWHVONVCYWRMZ-UHFFFAOYSA-N Note:

H O O

(+)-enantiomer

Pharmacological Data (10) 1 of 10

Comment (Pharmacological Data)

Bioactivities present

Badon, Lisa A.; Hicks, Alissa; Lord, Kevin; Ogden, Brian A.; Meleg-Smith, Suzanne; Varner, Kurt J.; Journal of Pharmacology and Experimental Therapeutics; vol. 302; nb. 3; (2002); p. 898 - 907, View in Reaxys 2 of 10

Effect (Pharmacological Data)

arterial pressure; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intravenous

Concentration (Pharmacological Data)

3 - 9 mg/kg

Kind of Dosing (Pharmacological Data)

injected in 28-34 μl with 100 μl of saline flush, twice daily (at 9:00 AM, at ca. 4:00 PM) within each of three 4-d binge separated by 10 d

Method (Pharmacological Data)

MAP continuously recorded using radio telemetry system for 30 - 45 min before and 1 h after each title comp. dose, averaged into 2-s bins

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Further Details (Pharmacological Data)

MAP: mean arterial pressure; further investigation with atropine (on 11th day after last 9 mg/kg title comp. dose within 3 binge atropine injected before additional 9 mg/kg title comp. injection)

Results

title comp. at 3 mg/kg induced ca. 40-mmHg MAP increase after each dose; at 9 mg/kg decreased MAP immediately after first 2, 3 doses during 2d, 3d binge, resp., via vagal activation, then induced ca. 40-mmHg MAP increase; no effect on baseline MAP

Effect (Pharmacological Data)

heart rate; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intravenous

Concentration (Pharmacological Data)

3 - 9 mg/kg

Kind of Dosing (Pharmacological Data)

injected in 28-34 μl, with 100 μl of saline flush; administered twice daily (at 9:00 AM, at ca. 4:00 PM) within each of three 4-d binge separated by 10 d

Method (Pharmacological Data)

HR continuously recorded using radio telemetry system for 30 - 45 min before and 1 h after each title comp. dose, averaged into 2-s bins

Further Details (Pharmacological Data)

HR: heart rate; further investigation with atropine (on 11th day after last 9 mg/kg title comp. dose within 3 binge atropine injected before additional 9 mg/kg title comp. injection)

Results

title comp. induced initial vagally mediated bradycardia followed by tachycardia; effects similar within 1st binge, lager tachycardia after 1st 3 mg/kg dose of 2d, 3d binge and lager bradycardia after first 2d, 3d 9 mg/kg dose of 2d, 3d binge, resp.

Effect (Pharmacological Data)

cardiotoxic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intravenous

Concentration (Pharmacological Data)

3 - 9 mg/kg

Kind of Dosing (Pharmacological Data)

injected in 28-34 μl with 100 μl of saline flush; administered twice daily (at 9:00 AM, at ca. 4:00 PM) within each of three 4-d binge separated by 10 d

Method (Pharmacological Data)

ECG analysed in freely moving rat for 30 - 45 min before and 1 h after 1st title comp. dose in 1st binge, after 1st, last (8th) title comp. doses in 2d and 3d binges

Further Details (Pharmacological Data)

HR: heart rate; further investigation with atropine (on 11th day after last 9 mg/kg title comp. dose within 3 binge atropine injected before additional 9 mg/kg title comp. injection)

Results

title comp. induced 7-10 extrasystoles/min for ca. 3 min immediately after each dose, 10-15-s vagally mediated sinus pause/heart block (more frequently after 1st dose in binge, in 2d, 3d binge), ST segment depression increasing as dosing progressed

Effect (Pharmacological Data)

antihypotensive

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intravenous

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Concentration (Pharmacological Data)

3 - 9 mg/kg

Kind of Dosing (Pharmacological Data)

injected in 28-34 μl with 100 μl of saline flush; administered twice daily (at 9:00 AM, at ca. 4:00 PM) within each of three 4-d binge separated by 10 d

Method (Pharmacological Data)

45 μg/kg sodium nitroprusside, i.v., injected 1 d before each title comp. binge and 10 d after 3d binge; MAP measured in freely moving rat using radio telemetry system

Further Details (Pharmacological Data)

MAP: mean arterial pressure

Results

title comp. at 3 mg/kg reduced magnitude of sodium nitroprusside-induced depressor response at all time points, while at 9 mg/kg sign. reduced it only 10 d after 3d binge

Effect (Pharmacological Data)

antihypotensive

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intravenous

Concentration (Pharmacological Data)

3 - 9 mg/kg

Kind of Dosing (Pharmacological Data)

injected in 28-34 μl with 100 μl of saline flush; administered twice daily (at 9:00 AM, at ca. 4:00 PM) within each of three 4-d binge separated by 10 d

Method (Pharmacological Data)

6 μg/kg acetylcholine, i.v., injected 1 d before each title comp. binge and 10 d after 3d binge; MAP measured in freely moving rat using radio telemetry system

Further Details (Pharmacological Data)

MAP: mean arterial pressure

Results

title comp. at 3 mg/kg reduced magnitude of acetylcholine-induced depressor response 10 d after last binge, while at 9 mg/kg increased depressor respose 1 d before 3d binge

Effect (Pharmacological Data)

antihypertensive, other

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intravenous

Concentration (Pharmacological Data)

3 - 9 mg/kg

Kind of Dosing (Pharmacological Data)

injected in 28-34 μl with 100 μl of saline flush; administered twice daily (at 9:00 AM, at ca. 4:00 PM) within each of three 4-d binge separated by 10 d

Method (Pharmacological Data)

9 μg/kg phenylephrine, i.v., injected 1 d before each title comp. binge and 10 d after 3d binge; MAP measured in freely moving rat using radio telemetry system to estimate effect on phenylephrine-induced hypertension

Further Details (Pharmacological Data)

MAP: mean arterial pressure

Comment (Pharmacological Data)

No effect

Effect (Pharmacological Data)

heart rate; effect on

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Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intravenous

Concentration (Pharmacological Data)

3 - 9 mg/kg

Kind of Dosing (Pharmacological Data)

injected in 28-34 μl with 100 μl of saline flush; administered twice daily (at 9:00 AM, at ca. 4:00 PM) within each of three 4-d binge separated by 10 d

Method (Pharmacological Data)

acetylcholine, sodium nitroprusside, phenylephrine, or 5-HT, i.v., injected 1 d before each title comp. binge and 10 d after 3d binge; HR measured in freely moving rat using radio telemetry system

Further Details (Pharmacological Data)

HR: heart rate; 5-HT: serotonin

Comment (Pharmacological Data)

No effect

Effect (Pharmacological Data)

hypotensive

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intravenous

Concentration (Pharmacological Data)

3 - 9 mg/kg

Kind of Dosing (Pharmacological Data)

injected in 28-34 μl with 100 μl of saline flush; administered twice daily (at 9:00 AM, at ca. 4:00 PM) within each of three 4-d binge separated by 10 d

Method (Pharmacological Data)

10 or 20 μg/kg 5-HT, i.v., injected 1 d before each title comp. binge and 10 d after 3d binge; MAP measured in freely moving rat using radio telemetry system

Further Details (Pharmacological Data)

MAP: mean arterial pressure; 5-HT: serotonin

Results

title comp. increased hypotesive response (ca. -40 versus ca. 2 - 8 mmHg) induced by 10 μg/kg 5-HT before 3d binge (figure); no effect at other points

Effect (Pharmacological Data)

cardiotoxic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intravenous

Concentration (Pharmacological Data)

9 mg/kg

Kind of Dosing (Pharmacological Data)

injected in 28-34 μl with 100 μl of saline flush; administered twice daily (at 9:00 AM, at ca. 4:00 PM) within each of three 4-d binge separated by 10 d

Method (Pharmacological Data)

heart removed 1 day after 1st and 3d title comp. binge, sectioned, stained with Mason's trichrome or hematoxylin-eosin followed by additional immunohistochemical analysis

Further Details (Pharmacological Data)

control: saline; positive control: intestine, spleen histological sections

Results

title comp. significantly increased lesions after 3d binge (total number 31 versus 6): multifocal inflammatory lesions (predominantly lymphocytic with lesser monocytes number) in both ventricles with and without obvious necrosis

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Reaxys ID 15723827 View in Reaxys

2H 2H

35/52 CAS Registry Number: 1005479-77-5 Chemical Name: d2-N-methyl-1-(3,4-methylenedioxyphenyl)-2aminopropane hydrochloride Linear Structure Formula: C11H13 (2)H2NO2*ClH Molecular Formula: C11H15NO2*ClH Molecular Weight: 231.691 InChI Key: LUWHVONVCYWRMZ-YNWPSCTISA-N Note:

H N HCl

Patent-Specific Data (1) References Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys Crystal Property Description (1) Colour & Other References Properties white

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

NMR Spectroscopy (1) 1 of 1

Nucleus (NMR Spectroscopy)

Solvents (NMR Spectro- chloroform-d1 scopy) Frequency (NMR Spectroscopy) [MHz]

300

Original Text (NMR Spectroscopy)

1H NMR (300MHz, CDCl ), δ 9.67 (s, 2H), 6.76-6.66 (m, 3H), 3.40-3.27 (m, 3H), 2.81-2.77 3 (m, IH), 2.70 (s, 3H), 1.35 (d, 3H, 7=6.6 Hz)

Comment (NMR Spectroscopy)

Signals given

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys Mass Spectrometry (1) Description (Mass Comment (Mass Spectrometry) Spectrometry) LCMS (Liquid chromatography mass spectrometry)

References

Molecular peak

Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

Reaxys ID 15723829 View in Reaxys

2H 2

O O

36/52

H N

CAS Registry Number: 1005479-78-6 Chemical Name: d5-N-methyl-1-(3,4-methylenedioxyphenyl)-2aminopropane hydrochloride Linear Structure Formula: C11H10 (2)H5NO2*ClH Molecular Formula: C11H15NO2*ClH Molecular Weight: 234.667 InChI Key: LUWHVONVCYWRMZ-WSMQZUBRSA-N Note:

HCl

Patent-Specific Data (1) References Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

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NMR Spectroscopy (1) 1 of 1

Nucleus (NMR Spectroscopy)

Solvents (NMR Spectro- chloroform-d1 scopy) Frequency (NMR Spectroscopy) [MHz]

300

Original Text (NMR Spectroscopy)

1H NMR (300MHz CDCl ), δ 9.66 (s, 2H), 6.78-6.66 (m, 3H), 3.37 (dd, IH, J=3.9, 12.9 5 3 Hz), 3.26 (br. s, IH), 2.77 (t, IH, J=12.6 Hz), 1.35 (d, 3H, J=6.6 Hz)

Comment (NMR Spectroscopy)

Signals given

Molecular peak

References Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

Reaxys ID 26969016 View in Reaxys

37/52 CAS Registry Number: 1536079-50-1 Chemical Name: DL-[13C6]-3,4-methylenedioxy-N-methylamphetamine hydrochloride Linear Structure Formula: C5 (13)C6H15NO2*ClH Molecular Formula: C11H15NO2*ClH Molecular Weight: 235.641 InChI Key: LUWHVONVCYWRMZ-GUDWOQMWSA-N Note:

O 13 C O

13C

13C 13CH

HCl

Substance Label (1) Label References 3b

Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387, View in Reaxys

Melting Point (1) 1 of 1

Melting Point [°C]

249.5 - 250.1

Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387, View in Reaxys

NMR Spectroscopy (2) 1 of 2

Description (NMR Spec- Chemical shifts troscopy) Nucleus (NMR Spectroscopy)

Coupling Nuclei

Solvents (NMR Spectro- dimethyl sulfoxide scopy) Frequency (NMR Spectroscopy) [MHz]

400

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Description (NMR Spec- Chemical shifts troscopy) Nucleus (NMR Spectroscopy)

13C

Solvents (NMR Spectro- dimethylsulfoxide-d6 scopy) Frequency (NMR Spectroscopy) [MHz]

100

Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387, View in Reaxys Mass Spectrometry (1) Description (Mass References Spectrometry) high resolution Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelmass spectrome- led Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387, View in Reaxys try (HRMS); spectrum

Reaxys ID 15723830 View in Reaxys 2H

2H 2H

H N

2H 2H

38/52 Chemical Name: d14-N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane d2-hydrochloride Linear Structure Formula: C11H(2)H14NO2*Cl(2)H Molecular Formula: C11H15NO2*ClH Molecular Weight: 244.587 InChI Key: LUWHVONVCYWRMZ-BUYDTYCHSA-N Note:

2H 2H

Patent-Specific Data (1) References Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English, View in Reaxys

Reaxys ID 20382306 View in Reaxys

39/52 CAS Registry Number: 1228259-59-3 Chemical Name: 3,4-methylendioxymethamphetamine oxalate; N,α-dimethyl-2-(3,4-methylenedioxyphenyl)ethylamine oxalate Linear Structure Formula: C2H2O4*C11H15NO2 Molecular Formula: C2H2O4*C11H15NO2 Molecular Weight: 283.281 InChI Key: GRBUROWYHWJKSU-UHFFFAOYSA-N Note:

O H N

OH O

Melting Point (1) 1 of 1

Melting Point [°C]

105 - 107

Schulze, Matthias; Synthetic Communications; vol. 40; nb. 10; (2010); p. 1461 - 1476, View in Reaxys Crystal Property Description (1) Colour & Other References Properties white

Schulze, Matthias; Synthetic Communications; vol. 40; nb. 10; (2010); p. 1461 - 1476, View in Reaxys

NMR Spectroscopy (2) 1 of 2

Description (NMR Spec- Chemical shifts troscopy)

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Nucleus (NMR Spectroscopy)

Solvents (NMR Spectro- dimethylsulfoxide-d6 scopy) Frequency (NMR Spectroscopy) [MHz]

300

Schulze, Matthias; Synthetic Communications; vol. 40; nb. 10; (2010); p. 1461 - 1476, View in Reaxys 2 of 2

Description (NMR Spec- Chemical shifts troscopy) Nucleus (NMR Spectroscopy)

13C

Solvents (NMR Spectro- dimethylsulfoxide-d6 scopy) Frequency (NMR Spectroscopy) [MHz]

Schulze, Matthias; Synthetic Communications; vol. 40; nb. 10; (2010); p. 1461 - 1476, View in Reaxys

Reaxys ID 26969017 View in Reaxys

40/52

H 13C O 13 13C C O

13C

Linear Structure Formula: C5 (13)C6H15NO2*C2HF3O2 Molecular Formula: C2HF3O2*C11H15NO2 Molecular Weight: 313.204 InChI Key: FRSPSMJHXFYNPJ-GUDWOQMWSA-N Note:

13CH

NH HO F

Mass Spectrometry (1) Description (Mass References Spectrometry) electron impact (EI); spectrum

Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387, View in Reaxys

Reaxys ID 22356071 View in Reaxys

41/52 Linear Structure Formula: C11H15NO2*C50H34N8O3 Molecular Formula: C11H15NO2*C50H34N8O3 Molecular Weight: 988.117 InChI Key: YUBRCWWWKTZTDR-NIFFTEIASA-N Note:

O HN

O H N

H N O

NH NH

Fluorescence Spectroscopy (1)

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Description (Fluo- Location rescence Spectroscopy)

References

Fluorescence

Moreno, Daniel; Grenu, Borja Diaz De; Garcia, Begona; Ibeas, Saturnino; Torroba, Tomas; Chemical Communications; vol. 48; nb. 24; (2012); p. 2994 - 2996, View in Reaxys

supporting information

Reaxys ID 27418548 View in Reaxys

O O O P

42/52 Linear Structure Formula: C68H68O12P4*C11H15NO2*ClH*H2O Molecular Formula: C11H15NO2*C68H68O12P4*ClH*H2O Molecular Weight: 1448.9 InChI Key: BNVHGSWIMXWYPO-UHFFFAOYSA-N Note:

O P O O O

O P O O

P O O

N H H 2O

HCl

Substance Label (1) Label References 1; Tiiii*MDMA

Density (1) 1 of 1

Density [g·cm-3]

1.276

Measurement Temperature [°C]

-83.16

Type (Density)

crystallographic

Location

supporting information

Biavardi, Elisa; Menozzi, Daniela; Massera, Chiara; Dalcanale, Enrico; Federici, Stefania; Sottini, Andrea; Bergese, Paolo; Tudisco, Cristina; Condorelli, Guglielmo G.; Angewandte Chemie, International Edition; vol. 53; nb. 35; (2014); p. 9183 - 9188,6; Angewandte Chemie; vol. 126; nb. 35; (2014); p. 9337 - 9342,6, View in Reaxys Crystal Phase (2) Description (Crys- Location tal Phase)

References

Structure of the solid

supporting information

Crystal growth

supporting information

Crystal System (1) Crystal System Location Triclinic

Space Group (1) Space Group 2

References

supporting information

Location

Comment (Space Group)

References

supporting information

a = 13.411 Å; b = 14.038 Å; c = 23.456 Å; α =

Biavardi, Elisa; Menozzi, Daniela; Massera, Chiara; Dalcanale, Enrico; Federici, Stefania; Sottini, Andrea; Bergese, Paolo; Tudisco, Cristina; Condorelli, Guglielmo G.; Angewandte Chemie,

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96.317 °; β = 104.227 °; γ = 114.786 °; Z = 2; T = 190 K; Method = Single crystal X-ray diffraction

International Edition; vol. 53; nb. 35; (2014); p. 9183 - 9188,6; Angewandte Chemie; vol. 126; nb. 35; (2014); p. 9337 - 9342,6, View in Reaxys

NMR Spectroscopy (2) 1 of 2

Description (NMR Spec- Spectrum troscopy) Nucleus (NMR Spectroscopy)

Solvents (NMR Spectro- methanol-d4 scopy) Temperature (NMR Spectroscopy) [°C]

24.84

Frequency (NMR Spectroscopy) [MHz]

400

Location

supporting information

Description (NMR Spec- Spectrum troscopy) Nucleus (NMR Spectroscopy)

31P

Solvents (NMR Spectro- methanol-d4 scopy) Biavardi, Elisa; Menozzi, Daniela; Massera, Chiara; Dalcanale, Enrico; Federici, Stefania; Sottini, Andrea; Bergese, Paolo; Tudisco, Cristina; Condorelli, Guglielmo G.; Angewandte Chemie, International Edition; vol. 53; nb. 35; (2014); p. 9183 - 9188,6; Angewandte Chemie; vol. 126; nb. 35; (2014); p. 9337 - 9342,6, View in Reaxys

Reaxys ID 10148545 View in Reaxys

43/52 Chemical Name: 3,4-methylenedioxymethamphetamine, 100 μmol/l; malonic acid disodium salt, 100 mmol/l; mixture of Type of Substance: mixture (composition partially given) Composition: Comp. Name: 5 (2 methylaminopropyl) 1,3 benzodioxole; disodium malonate

No Structure

Substance Label (1) Label References MDMA-MAL

Darvesh, Altaf S.; Yamamoto, Bryan K.; Gudelsky, Gary A.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 2; (2005); p. 694 - 701, View in Reaxys

Pharmacological Data (3) 1 of 3

Comment (Pharmacological Data)

Bioactivities present

Darvesh, Altaf S.; Yamamoto, Bryan K.; Gudelsky, Gary A.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 2; (2005); p. 694 - 701, View in Reaxys 2 of 3

Effect (Pharmacological Data)

neurotoxicity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intracerebral

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Kind of Dosing (Pharmacological Data)

dissolved in 0.15 mol/l NaCl; perfusion at flow rate of 1.8 μl/min for 8 h using dialysis probe implanted into striatum

Method (Pharmacological Data)

animals killed 5 d after treatment; brains removed; dopamine and serotonin content in striatal homogenate measured by HPLC with amperometric detection

Further Details (Pharmacological Data)

further investigation on mechanism of action using NO synthase inhibitors S-methyl-L-thiocitrulline and Nω-nitro-L-arginine methyl ester and peroxynitrile decomposition catalyst Fe(III)tetrakis(1-methyl-4-pyridyl)porphyrin

Results

title subst. resulted in 49 percent and 34 percent reduction of dopamine and serotonin levels, respectively; title subst.-induced neurotoxicity involved NO-dependent mechanism

Darvesh, Altaf S.; Yamamoto, Bryan K.; Gudelsky, Gary A.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 2; (2005); p. 694 - 701, View in Reaxys 3 of 3

Effect (Pharmacological Data)

hyperthermic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intracerebral

Kind of Dosing (Pharmacological Data)

dissolved in 0.15 mol/l NaCl

Method (Pharmacological Data)

title subst. perfused at flow rate of 1.8 μl/min for 8 h using dialysis probe implanted into striatum; rectal temperature monitored

Comment (Pharmacological Data)

No effect

Darvesh, Altaf S.; Yamamoto, Bryan K.; Gudelsky, Gary A.; Journal of Pharmacology and Experimental Therapeutics; vol. 312; nb. 2; (2005); p. 694 - 701, View in Reaxys

Reaxys ID 11401139 View in Reaxys

44/52 Type of Substance: mixture (composition partially given) Composition: Comp. Name: MDMA hydrochloride; carbidopa, catechol-O-methyl transferase (COMT) inhibitor, levodopa; mixture of

No Structure Pharmacological Data (2) 1 of 2

Comment (Pharmacological Data)

Bioactivities present

Patent; Caron, Marc G.; Sotnikova, Tatyana D.; Gainetdinov, Raul R.; US2007/27208; (2007); (A1) English, View in Reaxys 2 of 2

Effect (Pharmacological Data)

locomotor activity

Species or Test-System (Pharmacological Data)

DAT-KO mouse

Sex

male and female

Route of Application

intraperitoneal

Method (Pharmacological Data)

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ratory Animals (National Institutes of Health publication No.865-23, Bethesda, Md., United States) with an approved protocol from the Duke University Institutional Animal Care and Use Committee. C57BL/6J3129Sv/J hybrid WT and DAT-KO mice, 3-5 mo old, of both sexes were used. None of animals used in these studies had the neurodegenerative phenotype sporadically observed in DAT-KO mice [60]. Drugs. Drugs or saline (0.9percent NaCl) were administered intraperitoneally (IP) or subcutaneously (SC) in a volume of 10 ml/kg. The drags were either from Sigma (St. Louis, Mo., United States) or supplied by the National Institute of Drug Abuse (NIDA). Drugs provided by the NIDA Drug Supply Program included: (+/-)-MDMA, (+)-MDMA, (+/-)-6-OH-MDA, (+/-)-MDA, (+/-)-MDE, (+)-MDE, (-)-MDE, and AFT (alpha-ethyl-tryptamine acetate). Neurochemical assessments. Striatal tissue contents of DA and frontal cortical tissue levels of NE were assessed using HPLCEC (high performance liquid chromatography with electrochemical detection) as described [8]. In vivo microdialysis measurements of striatal extracellular DA levels in freely moving mice were performed at least 24 h after implantation of a microdialysis probe as described previously [50]. Dialysate samples were assayed for DA using HPLC-EC. Behavioral methods. Locomotor activity of littermate WT and DATKO mice was measured in an Omnitech CCDigiscan (Accuscan Instruments, Columbus, Ohio United States) activity monitor under bright illumination [83]. All behavioral experiments were performed between 10:00 AM and 5:00 PM. Activity was measured at 5-min intervals, To evaluate the effects of drugs on motor behaviors, mice were placed into activity monitor chambers (20.x.20 cm) for 30 min and then treated with αMT (250 mg/kg IP). A drug or combination of drugs were injected 1 h after αMT administration, and various parameters of locomotor activity were monitored for up to 3 h. In cumulative dosing experiments, animals were treated with increasing doses of drugs after a 1-h interval. For the akinesia test, the mouse is held by the tail so that it is standing on forelimbs only and moving on its own. The number of steps taken with both forelimbs was recorded during a 30-s trial [57]. The presence of catalepsy was determined and measured by placing the animal's forepaws on a horizontal wooden bar (0.7 cm in diameter), 4 cm above the tabletop. The time until the mouse removed both forepaws from the bar was recorded, with a maximum cut-off time of 3 min [53]. In the grasping test of muscular rigidity, the mouse is suspended by its forelimbs on a metal rod (diameter: 0.25 cm) positioned approximately 20 cm above the table. The time the animal remains on the rod (maximum 1 min) was noted [58]. To assess rigidity in a bracing task, the number of steps taken with each forelimb when the mouse is pushed sideways over a distance of 50 cm was recorded [57]. Tremor was scored visually in mice using the rating scale [54]: 0, no tremor; 1, occasional isolated twi Results

potent synergistic effect of L-DOPA/carbidopa and (+)-MDMA was observed; figure is given

Location

Page/Page column 3-4; 12-15; sheet 10

Patent; Caron, Marc G.; Sotnikova, Tatyana D.; Gainetdinov, Raul R.; US2007/27208; (2007); (A1) English, View in Reaxys

Reaxys ID 24452338 View in Reaxys

45/52 Composition: Comp. Name: (+)-3,4-Methylenedioxymethamphetamine; (-)-3,4-Methylenedioxymethamphetamine Composition: Comp. Conc.: 50; 50

No Structure Pharmacological Data (1) 1 of 1

Comment (Pharmacological Data)

Bioactivities present

Oberlender; Nichols; Journal of Pharmacology and Experimental Therapeutics; vol. 255; nb. 3; (1990); p. 1098 1106, View in Reaxys

Reaxys ID 28191507 View in Reaxys

46/52 Type of Substance: mixture (composition partially given) Composition: Comp. Name: 5 (2 methylaminopropyl) 1,3 benzodioxole; 5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine

No Structure Substance Label (1)

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Label

References

MDMA+MK801

Collins, Stuart A.; Gudelsky, Gary A.; Yamamoto, Bryan K.; European Journal of Pharmacology; vol. 761; (2015); p. 95 - 100; Art.No: 69923, View in Reaxys

Pharmacological Data (1) 1 of 1

Comment (Pharmacological Data)

physiological behaviour discussed

Collins, Stuart A.; Gudelsky, Gary A.; Yamamoto, Bryan K.; European Journal of Pharmacology; vol. 761; (2015); p. 95 - 100; Art.No: 69923, View in Reaxys

Reaxys ID 28191508 View in Reaxys

47/52 Type of Substance: mixture (composition partially given) Composition: Comp. Name: 5 (2 methylaminopropyl) 1,3 benzodioxole; (R)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol

No Structure Substance Label (1) Label References MDMA +MDL100907

Collins, Stuart A.; Gudelsky, Gary A.; Yamamoto, Bryan K.; European Journal of Pharmacology; vol. 761; (2015); p. 95 - 100; Art.No: 69923, View in Reaxys

Pharmacological Data (1) 1 of 1

Comment (Pharmacological Data)

physiological behaviour discussed

Collins, Stuart A.; Gudelsky, Gary A.; Yamamoto, Bryan K.; European Journal of Pharmacology; vol. 761; (2015); p. 95 - 100; Art.No: 69923, View in Reaxys

Reaxys ID 29141686 View in Reaxys

48/52 Type of Substance: mixture (composition partially given) Composition: Comp. Name: (+)-3,4-Methylenedioxymethamphetamine; d-amphetamine

No Structure

Reaxys ID 29293369 View in Reaxys

49/52 Type of Substance: mixture (composition partially given) Composition: Comp. Name: (S)-3,4-methylenedioxymethamphetamine; monensin A sodium salt

No Structure Pharmacological Data (1) 1 of 1

Comment (Pharmacological Data)

physiological behaviour discussed

Reaxys ID 29608160 View in Reaxys

50/52 Type of Substance: mixture (composition partially given) Composition: Comp. Name: 3,4-methylenedioxymethamphetamine; 3-(2-aminoethyl)-1H-indol-5-ol

No Structure

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Pharmacological Data (1) 1 of 1

Comment (Pharmacological Data)

physiological behaviour discussed

Silva, Sónia; Carvalho, Félix; Fernandes, Eduarda; Antunes, Manuel J.; Cotrim, Maria Dulce; Toxicology in Vitro; vol. 34; (2016); p. 187 - 193, View in Reaxys

Reaxys ID 29608161 View in Reaxys

51/52 Type of Substance: mixture (composition partially given) Composition: Comp. Name: 3,4-methylenedioxymethamphetamine; ketanserine

No Structure Pharmacological Data (1) 1 of 1

Comment (Pharmacological Data)

physiological behaviour discussed

Silva, Sónia; Carvalho, Félix; Fernandes, Eduarda; Antunes, Manuel J.; Cotrim, Maria Dulce; Toxicology in Vitro; vol. 34; (2016); p. 187 - 193, View in Reaxys

Reaxys ID 29608162 View in Reaxys

52/52 Type of Substance: mixture (composition partially given) Composition: Comp. Name: 3,4-methylenedioxymethamphetamine; FLUOXETINE

No Structure Pharmacological Data (1) 1 of 1

Comment (Pharmacological Data)

physiological behaviour discussed

Silva, Sónia; Carvalho, Félix; Fernandes, Eduarda; Antunes, Manuel J.; Cotrim, Maria Dulce; Toxicology in Vitro; vol. 34; (2016); p. 187 - 193, View in Reaxys

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