4-chloro-N-(2-morpholinoethyl)benzamide [Moclobemide (Aurorix)] by Asch

Query Query O

Date

6 substances in Reaxys

2016-07-25 14h:51m:40s (EST)

O N

1. Query

Results

N H Cl

Search as: As drawn, No mixtures, No charges, No radicals

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Reaxys ID 9495754 View in Reaxys

1/6 Linear Structure Formula: C12 (11)CH17ClN2O2 Molecular Formula: C13H17ClN2O2 Molecular Weight: 267.732 Type of Substance: heterocyclic InChI Key: YHXISWVBGDMDLQ-HSGWXFLFSA-N Note:

Cl O

11C

N O

Substance Label (2) Label References [%11&C]5d

Nordeman, Patrik; Friis, Stig D.; Andersen, Thomas L.; Audrain, Hlne; Larhed, Mats; Skrydstrup, Troels; Antoni, Gunnar; Chemistry - A European Journal; vol. 21; nb. 49; (2015); p. 17601 - 17604, View in Reaxys

Karimi, Farhad; Langstroem, Bengt; European Journal of Organic Chemistry; nb. 11; (2003); p. 2132 2137, View in Reaxys

Chromatographic Data (1) Chromatographic Location data

References

HPLC (High performance liquid chromatography)

supporting information

Reaxys ID 530974 View in Reaxys

2/6 CAS Registry Number: 71320-77-9 Chemical Name: moclobemide; 4-Chloro-N-(2-morpholin-4-ylethyl)-benzamide; Moclobemide; 4-chloro-N-(2-morpholin-4ylethyl)benzamide; Aurorix®; Manerix.(R).; p-chloro-N-(2-morpholinoethyl)-benzamide Linear Structure Formula: C13H17ClN2O2 Molecular Formula: C13H17ClN2O2 Molecular Weight: 268.743 Type of Substance: heterocyclic InChI Key: YHXISWVBGDMDLQ-UHFFFAOYSA-N Note:

Cl O NH

N O

Substance Label (16) Label References 6

Iqbal, Naeem; Cho, Eun Jin; Journal of Organic Chemistry; vol. 81; nb. 5; (2016); p. 1905 - 1911, View in Reaxys

Gockel, Samuel N.; Hull, Kami L.; Organic Letters; vol. 17; nb. 13; (2015); p. 3236 - 3239, View in Reaxys

3ad

Ghosh, Subhash Chandra; Li, Cheng Chao; Zeng, Hua Chun; Ngiam, Joyce S. Y.; Seayad, Abdul M.; Chen, Anqi; Advanced Synthesis and Catalysis; vol. 356; nb. 2-3; (2014); p. 475 - 484, View in Reaxys

Tinnis, Fredrik; Verho, Oscar; Gustafson, Karl P. J.; Tai, Cheuk-Wai; Baeckvall, Jan-E.; Adolfsson, Hans; Chemistry - A European Journal; vol. 20; nb. 20; (2014); p. 5885 - 5889, View in Reaxys

Neta, Pedatsur; Farahani, Mahnaz; Simn-Manso, Yamil; Liang, Yuxue; Yang, Xiaoyu; Stein, Stephen E.; Rapid Communications in Mass Spectrometry; vol. 28; nb. 23; (2014); p. 2645 - 2660, View in Reaxys

Dang, Tuan T.; Zhu, Yinghuai; Ngiam, Joyce S. Y.; Ghosh, Subhash C.; Chen, Anqi; Seayad, Abdul M.; ACS Catalysis; vol. 3; nb. 6; (2013); p. 1406 - 1410, View in Reaxys

MOC

Vishnu Nayak; Ciftci-Yabanoglu; Jadav, Surender Singh; Jagrat, Monika; Sinha, Barij N.; Ucar; Jayaprakash, Venkatesan; European Journal of Medicinal Chemistry; vol. 69; (2013); p. 762 - 767, View in Reaxys

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Secci, Daniela; Bolasco, Adriana; Carradori, Simone; D'Ascenzio, Melissa; Nescatelli, Riccardo; Yanez, Matilde; European Journal of Medicinal Chemistry; vol. 58; (2012); p. 405 - 417, View in Reaxys

Chiou, Shih-Hwa; Ku, Hung-Hai; Tsai, Tung-Hu; Lin, Heng-Liang; Chen, Li-Hsin; Chien, Chan-Shiu; Ho, Larry L.-T.; Lee, Chen-Hsen; Chang, Yuh-Lih; British Journal of Pharmacology; vol. 148; nb. 5; (2006); p. 587 - 598, View in Reaxys

Merck 6247

Boland, Andre; Gerardy, Jean; Mossay, Danielle; Seutin, Vincent; European Journal of Pharmacology; vol. 466; nb. 1-2; (2003); p. 21 - 30, View in Reaxys

M. 6309.

Khan, Khalid Mohammed; Rahat, Shagufta; Choudhary, Muhammad Iqbal; Atta-ur-Rahman; Ghani, Usman; Perveen, Shahnaz; Khatoon, Shagufta; Dar, Ahsana; Malik, Abdul; Helvetica Chimica Acta; vol. 85; nb. 2; (2002); p. 559 - 570, View in Reaxys

M 6309

Dingemanse, Jasper; Wallnoefer, Andreas; Gieschke, Ronald; Guentert, Theodor; Amrein, Roman; Clinical Pharmacology and Therapeutics; vol. 63; nb. 4; (1998); p. 403 - 413, View in Reaxys; Levant, Beth; Morgan, Kimberly A.; Ahlgren-Beckendorf, Joy A.; Grandy, David K.; Chen, Kevin; Shih, Jean C.; Seif, Isabelle; Life Sciences; vol. 70; nb. 2; (2001); p. 229 - 241, View in Reaxys

Merck 6309

Nielsen, Karin Kramer; Flinois, Jean Pierre; Beaune, Phillippe; Brosen, Kim; Journal of Pharmacology and Experimental Therapeutics; vol. 277; nb. 3; (1996); p. 1659 - 1664, View in Reaxys; Bergstroem; Westerberg; Nemeth; Traut; Gross; Greger; Mueller-Peltzer; Safer; Eckernaes; Grahner; Langstroem; European Journal of Clinical Pharmacology; vol. 52; nb. 2; (1997); p. 121 - 128, View in Reaxys

M 6309, MOC

De Angelis, Luisa; Naunyn-Schmiedeberg's Archives of Pharmacology; vol. 354; nb. 3; (1996); p. 379 - 383, View in Reaxys

moclobemide

Mongeau, Raymond; Montigny, Claude De; Blier, Pierre; European Journal of Pharmacology; vol. 271; (1994); p. 121 - 130, View in Reaxys

Patent-Specific Data (1) References Patent; Le Guern, Marie-Emmanuelle; Girard, Philippe; Gillardin, Jean-Marie; Berthon-Cedille, Laurence; Hublot, Bernard; US2006/276472; (2006); (A1) English, View in Reaxys Derivative (1) Comment (Derivative)

References

Hydrochlorid

Patent; Hoffmann-LaRoche; DE2706179; (1977); Chem.Abstr.; vol. 88; nb. 121196, View in Reaxys

Melting Point (3) 1 of 3

Melting Point [°C]

134 - 136

Location

supporting information

Gockel, Samuel N.; Hull, Kami L.; Organic Letters; vol. 17; nb. 13; (2015); p. 3236 - 3239, View in Reaxys 2 of 3

Melting Point [°C]

135 - 137

Solvent (Melting Point)

propan-2-ol

Ghanbarpour, Alireza; Hadizadeh, Farzin; Piri, Faride; Rashidi-Ranjbar, Parviz; Pharmaceutica Acta Helvetiae; vol. 72; nb. 2; (1997); p. 119 - 122, View in Reaxys 3 of 3

Melting Point [°C]

137

Patent; Hoffmann-LaRoche; DE2706179; (1977); Chem.Abstr.; vol. 88; nb. 121196, View in Reaxys Density (1) 1 of 1

Density [g·cm-3]

1.31

Type (Density)

crystallographic

Wouters, J.; Moureau, F.; Norberg, B.; Evrard, G.; Durant, F.; Bulletin des Societes Chimiques Belges; vol. 102; nb. 5; (1993); p. 329 - 334, View in Reaxys Association (MCS) (2) 1 of 2

Description (Association UV/VIS spectrum of the complex (MCS)) Solvent (Association (MCS))

dioxane

Partner (Association (MCS))

H2ca

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Adikwu, Michael U.; Ofokansi, Kenneth C.; Attama, Anthony A.; Biological and Pharmaceutical Bulletin; vol. 21; nb. 12; (1998); p. 1243 - 1246, View in Reaxys 2 of 2

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

H2O

Temperature (Association (MCS)) [°C]

30 - 90

Partner (Association (MCS))

H2ca

Adikwu, Michael U.; Ofokansi, Kenneth C.; Attama, Anthony A.; Biological and Pharmaceutical Bulletin; vol. 21; nb. 12; (1998); p. 1243 - 1246, View in Reaxys Chromatographic Data (2) Chromatographic Location data

References

TLC (Thin layer chromatography)

Iqbal, Naeem; Cho, Eun Jin; Journal of Organic Chemistry; vol. 81; nb. 5; (2016); p. 1905 - 1911, View in Reaxys

TLC (Thin layer chromatography)

supporting information

Gockel, Samuel N.; Hull, Kami L.; Organic Letters; vol. 17; nb. 13; (2015); p. 3236 3239, View in Reaxys

Conformation (1) Object of Investi- References gation Conformation

Wouters, J.; Moureau, F.; Norberg, B.; Evrard, G.; Durant, F.; Bulletin des Societes Chimiques Belges; vol. 102; nb. 5; (1993); p. 329 - 334, View in Reaxys

Crystal Phase (2) Description (Crys- Comment (Crystal References tal Phase) Phase) Crystal structure determination

α=98.3 grad, β=113.9 grad, χ=104.1 grad, a=11.57 Angstroem, b=13.81 Angstroem, c=10 Angstroem, n=2.; Temperature: 293 K. Method of determination: Single Crystal X-ray Diffraction

Wouters, J.; Moureau, F.; Norberg, B.; Evrard, G.; Durant, F.; Bulletin des Societes Chimiques Belges; vol. 102; nb. 5; (1993); p. 329 - 334, View in Reaxys

Crystal structure determination

Wouters, J.; Moureau, F.; Norberg, B.; Evrard, G.; Durant, F.; Bulletin des Societes Chimiques Belges; vol. 102; nb. 5; (1993); p. 329 - 334, View in Reaxys

Crystal Property Description (5) Colour & Other Location Properties

References

white

Ghosh, Subhash Chandra; Li, Cheng Chao; Zeng, Hua Chun; Ngiam, Joyce S. Y.; Seayad, Abdul M.; Chen, Anqi; Advanced Synthesis and Catalysis; vol. 356; nb. 2-3; (2014); p. 475 - 484, View in Reaxys; Bantreil, Xavier; Kanfar, Nasreddine; Gehin, Nicolas; Golliard, Ethan; Ohlmann, Pauline; Martinez, Jean; Lamaty, Frederic; Tetrahedron; vol. 70; nb. 34; (2014); p. 5093 - 5099, View in Reaxys; Bantreil, Xavier; Kanfar, Nasreddine; Gehin, Nicolas; Golliard, Ethan; Ohlmann, Pauline; Martinez, Jean; Lamaty, Frdric; Tetrahedron; vol. 70; nb. 34; (2014); p. 5093 - 5099, View in Reaxys; Iqbal, Naeem; Cho, Eun Jin; Journal of Organic Chemistry; vol. 81; nb. 5; (2016); p. 1905 - 1911, View in Reaxys

white

supporting information

Gockel, Samuel N.; Hull, Kami L.; Organic Letters; vol. 17; nb. 13; (2015); p. 3236 3239, View in Reaxys

colourless

supporting information

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white

supporting information

Allen, C. Liana; Davulcu, Simge; Williams, Jonathan M. J.; Organic Letters; vol. 12; nb. 22; (2010); p. 5096 - 5099, View in Reaxys; Allen, C. Liana; Chhatwal, A. Rosie; Williams, Jonathan M. J.; Chemical Communications; vol. 48; nb. 5; (2012); p. 666 668, View in Reaxys; Kim, Dokyoung; Sambasivan, Sunderraman; Nam, Hyoseok; Ki, Hean Kim; Jin, Yong Kim; Joo, Taiha; Lee, Kyung-Ha; Kim, Kyong-Tai; Han Ahn, Kyo; Chemical Communications; vol. 48; nb. 54; (2012); p. 6833 - 6835, View in Reaxys

yellow

supporting information

Dang, Tuan T.; Zhu, Yinghuai; Ghosh, Subhash C.; Chen, Anqi; Chai, Christina L. L.; Seayad, Abdul M.; Chemical Communications; vol. 48; nb. 12; (2012); p. 1805 1807, View in Reaxys

Dissociation Exponent (3) 1 of 3

Dissociation Exponent (pK)

6.31

Temperature (Dissociation Exponent) [°C]

Solvent (Dissociation Exponent)

H2O

Method (Dissociation Exponent)

potentiometric

Type (Dissociation Exponent)

a1/apparent

Zagorevskii, V. A.; Val'dman, A. V.; Kozlovskaya, M. M.; Lopatina, K. I.; Sokolova, T. V.; et al.; Pharmaceutical Chemistry Journal; vol. 23; nb. 11; (1989); p. 873 - 879; Khimiko-Farmatsevticheskii Zhurnal; vol. 23; nb. 11; (1989); p. 1304 - 1309, View in Reaxys 2 of 3

Dissociation Exponent (pK)

5.25

Temperature (Dissociation Exponent) [°C]

Solvent (Dissociation Exponent)

ethanol; H2O

Method (Dissociation Exponent)

potentiometric

Type (Dissociation Exponent)

a1/apparent

Comment (Dissociation Exponent)

Ratio of solvents: 1:1

Type (Dissociation Exponent)

Raaflaub; Haefelfinger; Trautmann; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 1; (1984); p. 80 - 82, View in Reaxys Electrochemical Behaviour (1) Description (Elec- References trochemical Behaviour) Electrolytic dissociation / protonation equilibrium

Raaflaub; Haefelfinger; Trautmann; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 1; (1984); p. 80 82, View in Reaxys

Interatomic Distances and Angles (1) Description References Interatomic distances and angles

Wouters, J.; Moureau, F.; Norberg, B.; Evrard, G.; Durant, F.; Bulletin des Societes Chimiques Belges; vol. 102; nb. 5; (1993); p. 329 - 334, View in Reaxys

Liquid/Liquid Systems (MCS) (1)

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1 of 1

Description (Liquid/ Liquid Systems (MCS))

Distribution between solvent 1 + 2

Partner (Liquid/Liquid Systems (MCS))

buffer pH 7.5; n-octanol

Raaflaub; Haefelfinger; Trautmann; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 1; (1984); p. 80 - 82, View in Reaxys Partition octan-1-ol/water (MCS) (1) 1 of 1

Partition Constant POW

1.68

Matos, Maria Joo; Rodrguez-Enrquez, Fernanda; Vilar, Santiago; Santana, Lourdes; Uriarte, Eugenio; Hripcsak, George; Estrada, Martn; Rodrguez-Franco, Mara Isabel; Via, Dolores; Bioorganic and Medicinal Chemistry Letters; vol. 25; nb. 3; (2015); p. 642 - 648, View in Reaxys Solubility (MCS) (3) 1 of 3

Solubility [g·l-1]

0.134372

Saturation

in solution

Temperature (Solubility (MCS)) [°C]

Solvent (Solubility (MCS))

phosphate buffer

Alelyunas, Yun W.; Empfield, James R.; McCarthy, Dennis; Spreen, Russell C.; Bui, Khanh; Pelosi-Kilby, Luciana; Shen, Cindy; Bioorganic and Medicinal Chemistry Letters; vol. 20; nb. 24; (2010); p. 7312 - 7316, View in Reaxys 2 of 3

Solubility [g·l-1]

Saturation

in pure solvent

Temperature (Solubility (MCS)) [°C]

Solvent (Solubility (MCS))

various solvent(s)

Raaflaub; Haefelfinger; Trautmann; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 1; (1984); p. 80 - 82, View in Reaxys 3 of 3

Solubility [g·l-1]

26.6

Saturation

in pure solvent

Temperature (Solubility (MCS)) [°C]

Solvent (Solubility (MCS))

aq. HCl

Raaflaub; Haefelfinger; Trautmann; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 1; (1984); p. 80 - 82, View in Reaxys Space Group (1) Space Group 2

References Wouters, J.; Moureau, F.; Norberg, B.; Evrard, G.; Durant, F.; Bulletin des Societes Chimiques Belges; vol. 102; nb. 5; (1993); p. 329 - 334, View in Reaxys

NMR Spectroscopy (21) 1 of 21

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

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

600

Location

supporting information

Iqbal, Naeem; Cho, Eun Jin; Journal of Organic Chemistry; vol. 81; nb. 5; (2016); p. 1905 - 1911, View in Reaxys

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2 of 21

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

13C

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

151

Location

supporting information

Iqbal, Naeem; Cho, Eun Jin; Journal of Organic Chemistry; vol. 81; nb. 5; (2016); p. 1905 - 1911, View in Reaxys 3 of 21

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

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

500

Location

supporting information

Gockel, Samuel N.; Hull, Kami L.; Organic Letters; vol. 17; nb. 13; (2015); p. 3236 - 3239, View in Reaxys 4 of 21

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

13C

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

125

Location

supporting information

Gockel, Samuel N.; Hull, Kami L.; Organic Letters; vol. 17; nb. 13; (2015); p. 3236 - 3239, View in Reaxys 5 of 21

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

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

400

Location

supporting information

Lescot, Camille; Nielsen, Dennis U.; Makarov, Ilya S.; Lindhardt, Anders T.; Daasbjerg, Kim; Skrydstrup, Troels; Journal of the American Chemical Society; vol. 136; nb. 16; (2014); p. 6142 - 6147, View in Reaxys; Ghosh, Subhash Chandra; Li, Cheng Chao; Zeng, Hua Chun; Ngiam, Joyce S. Y.; Seayad, Abdul M.; Chen, Anqi; Advanced Synthesis and Catalysis; vol. 356; nb. 2-3; (2014); p. 475 - 484, View in Reaxys 6 of 21

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

13C

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

100

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Location

supporting information

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

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

200

Original Text (NMR Spectroscopy)

Location

supporting information

Signals [ppm]

7.72; 7.41; 6.78; 3.69 - 3.78; 3.54; 2.56 - 2.67; 2.46 - 2.56

Kind of signal

dd, J=8.9, 2.2 Hz, 2H; dd, J=8.9, 2.2 Hz, 2H; s, 1H; m, 4H; dd, J=11.4, 5.4 Hz, 2H; m, 2H; m, 4H

NMR (CDCl3, 200 MHz): δ (ppm)=7.72 (dd, J=8.9, 2.2 Hz, 2H), 7.41 (dd, J=8.9, 2.2 Hz, 2H), 6.78 (s, 1H), 3.78-3.69 (m, 4H), 3.54 (dd, J=11.4, 5.4 Hz, 2H), 2.67-2.56 (m, 2H), 2.56-2.46 (m, 4H)

Bantreil, Xavier; Kanfar, Nasreddine; Gehin, Nicolas; Golliard, Ethan; Ohlmann, Pauline; Martinez, Jean; Lamaty, Frederic; Tetrahedron; vol. 70; nb. 34; (2014); p. 5093 - 5099, View in Reaxys 8 of 21

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

13C

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

Original Text (NMR Spectroscopy)

13C

Location

supporting information

Signals [ppm]

166.4; 137.6; 133; 128.8; 128.4; 66.9; 56.9; 53.4; 36.2

NMR (CDCl3, 75 MHz): δ (ppm)=166.4, 137.6, 133.0, 128.8, 128.4, 66.9, 56.9, 53.4, 36.2

Bantreil, Xavier; Kanfar, Nasreddine; Gehin, Nicolas; Golliard, Ethan; Ohlmann, Pauline; Martinez, Jean; Lamaty, Frederic; Tetrahedron; vol. 70; nb. 34; (2014); p. 5093 - 5099, View in Reaxys 9 of 21

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

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

400

Location

supporting information

Tinnis, Fredrik; Verho, Oscar; Gustafson, Karl P. J.; Tai, Cheuk-Wai; Baeckvall, Jan-E.; Adolfsson, Hans; Chemistry - A European Journal; vol. 20; nb. 20; (2014); p. 5885 - 5889, View in Reaxys 10 of 21

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

13C

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

100

Location

supporting information

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

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

200

Original Text (NMR Spectroscopy)

Location

supporting information

Signals [ppm]

7.62 - 7.81; 7.33 - 7.47; 6.69; 3.64 - 3.87

Kind of signal

m, 2H; m, 2H; s, 1H; m, 4H

NMR (CDCl3, 200 MHz): δ (ppm)=7.81-7.62 (m, 2H), 7.47-7.33 (m, 2H), 6.69 (s, 1H), 3.87-3.64 (m, 4H)

Bantreil, Xavier; Kanfar, Nasreddine; Gehin, Nicolas; Golliard, Ethan; Ohlmann, Pauline; Martinez, Jean; Lamaty, Frdric; Tetrahedron; vol. 70; nb. 34; (2014); p. 5093 - 5099, View in Reaxys 12 of 21

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

13C

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

Original Text (NMR Spectroscopy)

13C

Location

supporting information

Signals [ppm]

166.7; 138.2; 132.6; 129.1; 128.6; 44.2; 41.9

NMR (CDCl3, 75 MHz): δ (ppm)=166.7, 138.2, 132.6, 129.1, 128.6, 44.2, 41.9

Bantreil, Xavier; Kanfar, Nasreddine; Gehin, Nicolas; Golliard, Ethan; Ohlmann, Pauline; Martinez, Jean; Lamaty, Frdric; Tetrahedron; vol. 70; nb. 34; (2014); p. 5093 - 5099, View in Reaxys 13 of 21

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

Solvents (NMR Spectro- chloroform-d1 scopy) Temperature (NMR Spectroscopy) [°C]

Frequency (NMR Spectroscopy) [MHz]

300

Location

supporting information

Allen, C. Liana; Chhatwal, A. Rosie; Williams, Jonathan M. J.; Chemical Communications; vol. 48; nb. 5; (2012); p. 666 - 668, View in Reaxys 14 of 21

Description (NMR Spec- Chemical shifts; Spectrum troscopy)

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Nucleus (NMR Spectroscopy)

13C

Solvents (NMR Spectro- chloroform-d1 scopy) Temperature (NMR Spectroscopy) [°C]

Frequency (NMR Spectroscopy) [MHz]

75.5

Location

supporting information

Allen, C. Liana; Chhatwal, A. Rosie; Williams, Jonathan M. J.; Chemical Communications; vol. 48; nb. 5; (2012); p. 666 - 668, View in Reaxys 15 of 21

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

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

300

Location

supporting information

Dang, Tuan T.; Zhu, Yinghuai; Ghosh, Subhash C.; Chen, Anqi; Chai, Christina L. L.; Seayad, Abdul M.; Chemical Communications; vol. 48; nb. 12; (2012); p. 1805 - 1807, View in Reaxys 16 of 21

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

Solvents (NMR Spectro- dimethylsulfoxide-d6 scopy) Temperature (NMR Spectroscopy) [°C]

19.84

Frequency (NMR Spectroscopy) [MHz]

300

Location

supporting information

Kim, Dokyoung; Sambasivan, Sunderraman; Nam, Hyoseok; Ki, Hean Kim; Jin, Yong Kim; Joo, Taiha; Lee, Kyung-Ha; Kim, Kyong-Tai; Han Ahn, Kyo; Chemical Communications; vol. 48; nb. 54; (2012); p. 6833 - 6835, View in Reaxys 17 of 21

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

13C

Solvents (NMR Spectro- dimethylsulfoxide-d6 scopy) Temperature (NMR Spectroscopy) [°C]

19.84

Frequency (NMR Spectroscopy) [MHz]

Location

supporting information

Description (NMR Spec- Chemical shifts; Spectrum troscopy)

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Nucleus (NMR Spectroscopy)

13C

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

Location

supporting information

Dang, Tuan T.; Zhu, Yinghuai; Ghosh, Subhash C.; Chen, Anqi; Chai, Christina L. L.; Seayad, Abdul M.; Chemical Communications; vol. 48; nb. 12; (2012); p. 1805 - 1807, View in Reaxys 19 of 21

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

Solvents (NMR Spectro- [(2)H6]acetone scopy) Frequency (NMR Spectroscopy) [MHz]

250

Location

supporting information

Allen, C. Liana; Davulcu, Simge; Williams, Jonathan M. J.; Organic Letters; vol. 12; nb. 22; (2010); p. 5096 5099, View in Reaxys 20 of 21

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

Solvents (NMR Spectro- CDCl3 scopy) Ghanbarpour, Alireza; Hadizadeh, Farzin; Piri, Faride; Rashidi-Ranjbar, Parviz; Pharmaceutica Acta Helvetiae; vol. 72; nb. 2; (1997); p. 119 - 122, View in Reaxys 21 of 21

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

13C

Description (IR Spectroscopy)

Bands

Solvent (IR Spectroscopy)

neat (no solvent, solid phase)

Iqbal, Naeem; Cho, Eun Jin; Journal of Organic Chemistry; vol. 81; nb. 5; (2016); p. 1905 - 1911, View in Reaxys 2 of 6

Description (IR Spectroscopy)

ATR (attenuated total reflectance); Bands

Location

supporting information

Gockel, Samuel N.; Hull, Kami L.; Organic Letters; vol. 17; nb. 13; (2015); p. 3236 - 3239, View in Reaxys 3 of 6

Description (IR Spectroscopy)

ATR-FTIR (attenuated total reflectance Fourier transform infrared spectroscopy); Bands

Location

supporting information

Allen, C. Liana; Chhatwal, A. Rosie; Williams, Jonathan M. J.; Chemical Communications; vol. 48; nb. 5; (2012); p. 666 - 668, View in Reaxys

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4 of 6

Description (IR Spectroscopy)

Bands

Location

supporting information

Allen, C. Liana; Davulcu, Simge; Williams, Jonathan M. J.; Organic Letters; vol. 12; nb. 22; (2010); p. 5096 5099, View in Reaxys 5 of 6

Description (IR Spectroscopy)

Bands

Solvent (IR Spectroscopy)

CCl4

Comment (IR Spectroscopy)

3425 - 1510 cm**(-1)

Description (IR Spectroscopy)

Bands

Solvent (IR Spectroscopy)

nujol

Comment (IR Spectroscopy)

3275 - 1540 cm**(-1)

References

high resolution supporting informass spectrome- mation try (HRMS); electrospray ionisation (ESI); timeof-flight mass spectra (TOFMS); spectrum

Gockel, Samuel N.; Hull, Kami L.; Organic Letters; vol. 17; nb. 13; (2015); p. 3236 3239, View in Reaxys

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

Sheng, Ling-Hui; Chen, Hong-Rui; Huo, Ying-Bin; Wang, Jing; Zhang, Yu; Yang, Min; Zhang, Hong-Xun; Molecules; vol. 19; nb. 1; (2014); p. 1212 - 1222, View in Reaxys

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

Ghosh, Subhash Chandra; Li, Cheng Chao; Zeng, Hua Chun; Ngiam, Joyce S. Y.; Seayad, Abdul M.; Chen, Anqi; Advanced Synthesis and Catalysis; vol. 356; nb. 2-3; (2014); p. 475 - 484, View in Reaxys; Vaikkinen, Anu; Shrestha, Bindesh; Koivisto, Juha; Kostiainen, Risto; Vertes, Akos; Kauppila, Tiina J.; Rapid Communications in Mass Spectrometry; vol. 28; nb. 23; (2014); p. 2490 - 2496, View in Reaxys

high resolution supporting informass spectrome- mation try (HRMS); spectrum

Lescot, Camille; Nielsen, Dennis U.; Makarov, Ilya S.; Lindhardt, Anders T.; Daasbjerg, Kim; Skrydstrup, Troels; Journal of the American Chemical Society; vol. 136; nb. 16; (2014); p. 6142 - 6147, View in Reaxys; Tinnis, Fredrik; Verho, Oscar; Gustafson, Karl P. J.; Tai, Cheuk-Wai; Baeckvall, Jan-E.; Adolfsson, Hans; Chemistry - A European Journal; vol. 20; nb. 20; (2014); p. 5885 - 5889, View in Reaxys

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

Neta, Pedatsur; Farahani, Mahnaz; Simn-Manso, Yamil; Liang, Yuxue; Yang, Xiaoyu; Stein, Stephen E.; Rapid Communications in Mass Spectrometry; vol. 28; nb. 23; (2014); p. 2645 - 2660, View in Reaxys

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

supporting information

Allen, C. Liana; Chhatwal, A. Rosie; Williams, Jonathan M. J.; Chemical Communications; vol. 48; nb. 5; (2012); p. 666 - 668, View in Reaxys

HRMS (High resolution mass spectrometry); Spectrum

supporting information

Dang, Tuan T.; Zhu, Yinghuai; Ghosh, Subhash C.; Chen, Anqi; Chai, Christina L. L.; Seayad, Abdul M.; Chemical Communications; vol. 48; nb. 12; (2012); p. 1805 1807, View in Reaxys

ESI (Electrospray ionisation); Spectrum

supporting information

Allen, C. Liana; Davulcu, Simge; Williams, Jonathan M. J.; Organic Letters; vol. 12; nb. 22; (2010); p. 5096 - 5099, View in Reaxys

spectrum

Ghanbarpour, Alireza; Hadizadeh, Farzin; Piri, Faride; Rashidi-Ranjbar, Parviz; Pharmaceutica Acta Helvetiae; vol. 72; nb. 2; (1997); p. 119 - 122, View in Reaxys

Pharmacological Data (239) 1 of 239

Comment (Pharmacological Data)

Bioactivities present

Patent; Hoffmann-La Roche Inc.; US4210754; (1980); (A1) English, View in Reaxys; Patent; H. Lundbeck A/S; US2003/138376; (2003); (A1) English, View in Reaxys; Patent; Palatin Technologies, Inc.; US2004/224957; (2004); (A1) English, View in Reaxys; Patent; Pendri, Annapurna; Gerritz, Samuel; Dodd, Dharmpal S.; Sun, Chongqing; US2005/80087; (2005); (A1) English, View in Reaxys; Patent; CNS Response; US2005/96311; (2005); (A1) English, View in Reaxys; Patent; SHELDON, Leslie James; WO2005/53703; (2005); (A1) English, View in Reaxys; Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys; Patent; KYOWA HAKKO KOGYO CO., LTD.; EP1655029; (2006); (A1) English, View in Reaxys; Patent; Universitaetsklinikum Freiburg; EP1693062; (2006); (A2) English, View in Reaxys; Patent; Le Guern, Marie-Emmanuelle; Girard, Philippe; Gillardin, Jean-Marie; Berthon-Cedille, Laurence; Hublot, Bernard; US2006/276472; (2006); (A1) English, View in Reaxys; Patent; Ewing, William R.; Zhu, Yeheng; Ellsworth, Bruce A.; US2006/287323; (2006); (A1) English, View in Reaxys; Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys; Patent; Bristol-Myers Squibb Company; US2007/93508; (2007); (A1) English, View in Reaxys; Patent; Rabinoff, Michael D; US2007/134169; (2007); (A1) English, View in Reaxys; Patent; BIRDS PHARMA GMBH BEROLINA INNOVATIVE RESEARCH and DEVELOPMENT SERVICES; WO2007/93450; (2007); (A2) English, View in Reaxys; Patent; CHELSEA THERAPEUTICS, INC.; WO2008/3028; (2008); (A2) English, View in Reaxys; Patent; HAAS, Magali; US2008/103127; (2008); (A1) English, View in Reaxys; Patent; Hoffmann-LaRoche; DE2706179; (1977); Chem.Abstr.; vol. 88; nb. 121196, View in Reaxys; Zagorevskii, V. A.; Val'dman, A. V.; Kozlovskaya, M. M.; Lopatina, K. I.; Sokolova, T. V.; et al.; Pharmaceutical Chemistry Journal; vol. 23; nb. 11; (1989); p. 873 - 879; Khimiko-Farmatsevticheskii Zhurnal; vol. 23; nb. 11; (1989); p. 1304 - 1309, View in Reaxys; Schlappi; Arzneimittel-Forschung/Drug Research; vol. 35; nb. 5; (1985); p. 800 - 803, View in Reaxys 2 of 239

Comment (Pharmacological Data)

Bioactivities present

Wouters, J.; Moureau, F.; Norberg, B.; Evrard, G.; Durant, F.; Bulletin des Societes Chimiques Belges; vol. 102; nb. 5; (1993); p. 329 - 334, View in Reaxys; Raaflaub; Haefelfinger; Trautmann; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 1; (1984); p. 80 - 82, View in Reaxys; Branca, Quirico; Jakob-Roetne, Roland; Kettler, Rolf; Roever, Stephan; Scalone, Michelangelo; Chimia; vol. 49; nb. 10; (1995); p. 381 - 385, View in Reaxys; Yesilada; Gokhan; Ozer; Vural; Erol; Farmaco; vol. 51; nb. 12; (1996); p. 775 - 780, View in Reaxys; Ghanbarpour, Alireza; Hadizadeh, Farzin; Piri, Faride; Rashidi-Ranjbar, Parviz; Pharmaceutica Acta Helvetiae; vol. 72; nb. 2; (1997); p. 119 - 122, View in Reaxys; Avramova, P. D.; Danchev, N. D.; Buyukliev, R. T.; European Journal of Medicinal Chemistry; vol. 31; nb. 11; (1996); p. 909 - 914, View in Reaxys; Avramova, Petya; Danchev, Nicolai; Buyukliev, Rossen; Bogoslovova, Tatiana; Archiv der Pharmazie; vol. 331; nb. 11; (1998); p. 342 - 346, View in Reaxys; Berlin, Ivan; Said, Sophie; Spreux-Varoquaux, Odile; Launay, Jean-Marie; Olivares, Robert; Millet, Veronique; Lecrubier, Yves; Puech, Alain J.; Clinical Pharmacology and Therapeutics; vol. 58; nb. 4; (1995); p. 444 - 452, View in Reaxys; Schwaninger; Schoefl; Blume; Roessig; Knepel; Molecular Pharmacology; vol. 47; nb. 6; (1995); p. 1112 - 1118, View in Reaxys; Gram, Lars F.; Guentert, Theodor W.; Grange, Susan; Vistisen, Kirsten; Broesen, Kim; Clinical Pharmacology & Therapeutics (New York, NY, United States); vol. 57; nb. 6; (1995); p. 670 677, View in Reaxys; Mongeau, Raymond; Montigny, Claude De; Blier, Pierre; European Journal of Pharmacology; vol. 271; (1994); p. 121 - 130, View in Reaxys; Andreeva; Pharmaceutical Chemistry Journal; vol. 30; nb. 6; (1996); p. 359 - 360, View in Reaxys; Andreeva; Golovina; Syubaev; Mashkovskii; Pharmaceutical Chemistry Journal; vol. 31; nb. 4; (1997); p. 166 - 167, View in Reaxys; Illi; Sundberg; Ojala-Karlsson; Scheinin; Gordin; Clinical Pharmacology and Therapeutics; vol. 59; nb. 4; (1996); p. 450 - 457, View in Reaxys; Nielsen, Karin Kramer; Flinois, Jean Pierre; Beaune, Phillippe; Brosen, Kim; Journal of Pharmacology and Experimental Therapeutics; vol. 277; nb. 3; (1996); p. 1659 - 1664, View in Reaxys; Korn; Wagner; Moritz; Dingemanse; European Jour-

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nal of Clinical Pharmacology; vol. 49; nb. 4; (1996); p. 273 - 278, View in Reaxys; Yoshida, Fumitaka; Topliss, John G.; Journal of Medicinal Chemistry; vol. 43; nb. 13; (2000); p. 2575 - 2585, View in Reaxys; De Angelis, Luisa; Naunyn-Schmiedeberg's Archives of Pharmacology; vol. 354; nb. 3; (1996); p. 379 - 383, View in Reaxys; Curet, Olivier; Damoiseau, Gabrielle; Aubin, Nadine; Sontag, Nicole; Rovei, Vincenzo; Jarreau, Francois-Xavier; Journal of Pharmacology and Experimental Therapeutics; vol. 277; nb. 1; (1996); p. 253 - 264, View in Reaxys; Caille, Dominique; Bergis, Olivier-Emmanuel; Fankhauser, Christine; Gardes, Arlette; Adam, Roselyne; Charieras, Thierry; Grosset, Alain; Rovei, Vincenzo; Jarreau, Francois-Xavier; Journal of Pharmacology and Experimental Therapeutics; vol. 277; nb. 1; (1996); p. 265 - 277, View in Reaxys 3 of 239

Comment (Pharmacological Data)

Bioactivities present

Kagaya, Takaki; Kajiwara, Akiharu; Nagato, Satoshi; Akasaka, Kozo; Kubota, Atsuhiko; Journal of Pharmacology and Experimental Therapeutics; vol. 278; nb. 1; (1996); p. 243 - 251, View in Reaxys; Hoskins; Shenfield; Murray; Gross; Xenobiotica; vol. 31; nb. 7; (2001); p. 387 - 397, View in Reaxys; Bergstroem; Westerberg; Nemeth; Traut; Gross; Greger; Mueller-Peltzer; Safer; Eckernaes; Grahner; Langstroem; European Journal of Clinical Pharmacology; vol. 52; nb. 2; (1997); p. 121 - 128, View in Reaxys; Kato, Masaya; Katayama, Taiichi; Iwata, Hiroshi; Yamamura, Michio; Matsuoka, Yuzo; Narita, Hiroshi; Journal of Pharmacology and Experimental Therapeutics; vol. 284; nb. 3; (1998); p. 983 - 990, View in Reaxys; Humphrey, Stephen J.; Curry, James T.; Turman, Chauncey N.; Stryd, Ronald P.; Journal of Cardiovascular Pharmacology; vol. 37; nb. 5; (2001); p. 548 - 563, View in Reaxys; Yu, Kyung-Sang; Yim, Dong-Seok; Cho, Joo-Youn; Park, Soon Seong; Park, Ji Young; Lee, Kyung-Hoon; Jang, In-Jin; Yi, So-Young; Bae, Kyun-Seop; Shin, Sang-Goo; Clinical Pharmacology and Therapeutics; vol. 69; nb. 4; (2001); p. 266 - 273, View in Reaxys; Khan, Khalid Mohammed; Rahat, Shagufta; Choudhary, Muhammad Iqbal; Atta-ur-Rahman; Ghani, Usman; Perveen, Shahnaz; Khatoon, Shagufta; Dar, Ahsana; Malik, Abdul; Helvetica Chimica Acta; vol. 85; nb. 2; (2002); p. 559 - 570, View in Reaxys; Adikwu, Michael U.; Ofokansi, Kenneth C.; Attama, Anthony A.; Biological and Pharmaceutical Bulletin; vol. 21; nb. 12; (1998); p. 1243 - 1246, View in Reaxys; Klopman, Gilles; Stefan, Liliana R; Saiakhov, Roustem D; European Journal of Pharmaceutical Sciences; vol. 17; nb. 4-5; (2002); p. 253 - 263, View in Reaxys; Lapatto-Reiniluoto; Kivistoe; Neuvonen; European Journal of Clinical Pharmacology; vol. 56; nb. 4; (2000); p. 285 - 288, View in Reaxys; Silvestri, Romano; La Regina, Giuseppe; De Martino, Gabriella; Artico, Marino; Befani, Olivia; Palumbo, Marianna; Agostinelli, Enzo; Turini, Paola; Journal of Medicinal Chemistry; vol. 46; nb. 6; (2003); p. 917 - 920, View in Reaxys; Dingemanse, Jasper; Wallnoefer, Andreas; Gieschke, Ronald; Guentert, Theodor; Amrein, Roman; Clinical Pharmacology and Therapeutics; vol. 63; nb. 4; (1998); p. 403 - 413, View in Reaxys; Bruno-Blanch; Galvez; Garcia-Domenech; Bioorganic and Medicinal Chemistry Letters; vol. 13; nb. 16; (2003); p. 2749 - 2754, View in Reaxys; Goekhan, Nesrin; Yesilada, Akguel; Ucar, Guelberk; Erol, Kevser; Bilgin, A. Altan; Archiv der Pharmazie; vol. 336; nb. 8; (2003); p. 362 - 371, View in Reaxys; Levant, Beth; Morgan, Kimberly A.; Ahlgren-Beckendorf, Joy A.; Grandy, David K.; Chen, Kevin; Shih, Jean C.; Seif, Isabelle; Life Sciences; vol. 70; nb. 2; (2001); p. 229 - 241, View in Reaxys; Dingemanse, Jasper; Guentert, Theodor; Gieschke, Ronald; Stabl, Max; Journal of Cardiovascular Pharmacology; vol. 28; nb. 6; (1996); p. 856 - 861, View in Reaxys; Bottlaender, Michel; Dolle, Frederic; Guenther, Ilonka; Roumenov, Dimitri; Fuseau, Chantal; Bramoulle, Yann; Curet, Olivier; Jegham, Jamir; Pinquier, Jean-Louis; George, Pascal; Valette, Heric; Journal of Pharmacology and Experimental Therapeutics; vol. 305; nb. 2; (2003); p. 467 - 473, View in Reaxys; Tatarczynska, Ewa; Klodzinska, Aleksandra; Stachowicz, Katarzyna; Chojnacka-Wojcik, Ewa; European Journal of Pharmacology; vol. 487; nb. 1-3; (2004); p. 133 - 142, View in Reaxys; Yoshida, Shinichi; Rosen, Thomas C.; Meyer, Oliver G.J.; Sloan, Milton J.; Ye, Song; Haufe, Guenter; Kirk, Kenneth L.; Bioorganic and Medicinal Chemistry; vol. 12; nb. 10; (2004); p. 2645 - 2652, 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 4 of 239

Comment (Pharmacological Data)

Bioactivities present

Aubin; Barneoud, Pascal; Carter; Caille; Sontag; Marc; Lolivier; Gardes; Perron; Le Kim; Charieras; Pandini; Burnier; Puech; Jegham; George; Scatton; Curet; Journal of Pharmacology and Experimental Therapeutics; vol. 310; nb. 3; (2004); p. 1171 - 1182, View in Reaxys; MacInnes, Nicholas; Duty, Susan; British Journal of Pharmacology; vol. 143; nb. 8; (2004); p. 952 - 959, View in Reaxys; Southam, Eric; Pereira, Rui; Stratton, Sharon C.; Sargent, Rebecca; Ford, Alison J.; Butterfield, Lindsay J.; Wheable, Jane D.; Beckett, Simon R.G.; Roe, Clare; Marsden, Charles A.; Hagan, Russell M.; European Journal of Pharmacology; vol. 519; nb. 3; (2005); p. 237 - 245, View in Reaxys; Di Santo, Roberto; Costi, Roberta; Roux, Alessandra; Artico, Marino; Befani, Olivia; Meninno, Tiziana; Agostinelli, Enzo; Palmegiani, Paola; Turini, Paola; Cirilli, Roberto; Ferretti, Rosella; Gallinella, Bruno; La Torre, Francesco; Journal of Medicinal Chemistry; vol. 48; nb. 13; (2005); p. 4220 - 4223, View in Reaxys; Obach, R. Scott; Walsky, Robert L.; Venkatakrishnan, Karthik; Gaman, Emily A.; Houston, J. Brian; Tremaine, Larry M.; Journal of Pharmacology and Experimental Therapeutics; vol. 316; nb. 1; (2006); p. 336 - 348, View in Reaxys; Boland, Andre; Gerardy, Jean; Mossay, Danielle; Seutin, Vincent; European Journal of Pharmacology; vol. 466; nb. 1-2; (2003); p. 21 - 30, View in Reaxys; Nielsen, Torben Leo; Rasmussen, Birgitte Buur; Flinois, Jean-Pierre; Beaune, Philippe; Brosen, Kim; Journal of Pharmacology and Experimental Therapeutics; vol. 289; nb. 1; (1999); p. 31 - 37, View in Reaxys; Ulus, Ismail H.; Maher, Timothy J.; Wurtman, Richard J.; Biochemical Pharmacology; vol. 59; nb. 12; (2000); p. 1611 - 1621, 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; Levant; Moehlenkamp; Morgan; Leonard; Cheng; The Journal of pharmacology and experimental therapeutics; vol. 278; nb. 1; (1996); p. 145 - 153, View in Reaxys; Vilpoux, Catherine; Carpentier, Celine; Leroux-Nicollet, Isabelle; Naudon, Laurent; Costentin, Jean; European Journal of Pharmacology; vol. 443; nb. 1-3; (2002); p. 85 - 93, View in Reaxys; Chiou, Shih-Hwa;

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2016-07-25 15:01:51

Ku, Hung-Hai; Tsai, Tung-Hu; Lin, Heng-Liang; Chen, Li-Hsin; Chien, Chan-Shiu; Ho, Larry L.-T.; Lee, ChenHsen; Chang, Yuh-Lih; British Journal of Pharmacology; vol. 148; nb. 5; (2006); p. 587 - 598, View in Reaxys; Chimenti, Franco; Fioravanti, Rossella; Bolasco, Adriana; Manna, Fedele; Chimenti, Paola; Secci, Daniela; Befani, Olivia; Turini, Paola; Ortuso, Francesco; Alcaro, Stefano; Journal of Medicinal Chemistry; vol. 50; nb. 3; (2007); p. 425 - 428, View in Reaxys; La Regina, Giuseppe; Silvestri, Romano; Artico, Marino; Lavecchia, Antonio; Novellino, Ettore; Befani, Olivia; Turini, Paola; Agostinelli, Enzo; Journal of Medicinal Chemistry; vol. 50; nb. 5; (2007); p. 922 - 931, View in Reaxys; Wesolowska, Anna; Tatarczynska, Ewa; Nikiforuk, Agnieszka; Chojnacka-Wojcik, Ewa; European Journal of Pharmacology; vol. 555; nb. 1; (2007); p. 43 - 47, View in Reaxys; Patent; Hoechst-Roussel Pharmaceutical Incorporated; US5494908; (1996); (A1) English, View in Reaxys; Wesolowska, Anna; Nikiforuk, Agnieszka; European Journal of Pharmacology; vol. 582; nb. 1-3; (2008); p. 88 - 93, View in Reaxys; Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys; Patent; Chelsea Therapeutics, Inc.; US2008/227830; (2008); (A1) English, View in Reaxys; Patent; THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK; WO2008/100727; (2008); (A2) English, View in Reaxys 5 of 239

Comment (Pharmacological Data)

Bioactivities present

Patent; SEED, John, C.; WO2005/51297; (2005); (A2) English, View in Reaxys; Chimenti, Franco; Fioravanti, Rossella; Bolasco, Adriana; Manna, Fedele; Chimenti, Paola; Secci, Daniela; Rossi, Francesca; Turini, Paola; Ortuso, Francesco; Alcaro, Stefano; Cardia, Maria Cristina; European Journal of Medicinal Chemistry; vol. 43; nb. 10; (2008); p. 2262 - 2267, View in Reaxys; La Regina, Giuseppe; Silvestri, Romano; Gatti, Valerio; Lavecchia, Antonio; Novellino, Ettore; Befani, Olivia; Turini, Paola; Agostinelli, Enzo; Bioorganic and Medicinal Chemistry; vol. 16; nb. 22; (2008); p. 9729 - 9740, View in Reaxys; Patent; UNIVERSIDADE DE SANTIAGO DE COMPOSTELA; WO2009/34216; (2009); (A1) Spanish, View in Reaxys; Goekhan-Kelekci, Nesrin; Koyunoglu, Semra; Yabanoglu, Samiye; Yelekci, Kemal; Oezgen, Oezen; Ucar, Guelberk; Erol, Kevser; Kendi, Engin; Yesilada, Akguel; Bioorganic and Medicinal Chemistry; vol. 17; nb. 2; (2009); p. 675 - 689, View in Reaxys; Chimenti, Franco; Maccioni, Elias; Secci, Daniela; Bolasco, Adriana; Chimenti, Paola; Granese, Arianna; Carradori, Simone; Alcaro, Stefano; Ortuso, Francesco; Yanez, Matilde; Orallo, Francisco; Cirilli, Roberto; Ferretti, Rosella; La Torre, Francesco; Journal of Medicinal Chemistry; vol. 51; nb. 16; (2008); p. 4874 - 4880, View in Reaxys; Jayaprakash, Venkatesan; Sinha, Barij N.; Ucar, Gulberk; Ercan, Ayse; Bioorganic and Medicinal Chemistry Letters; vol. 18; nb. 24; (2008); p. 6362 - 6368, View in Reaxys; Santana, Lourdes; Gonzalez-Diaz, Humberto; Quezada, Elias; Uriarte, Eugenio; Yanez, Matilde; Vina, Dolores; Orallo, Francisco; Journal of Medicinal Chemistry; vol. 51; nb. 21; (2008); p. 6740 - 6751, View in Reaxys; Allen, C. Liana; Lapkin, Alexei A.; Williams, Jonathan M.J.; Tetrahedron Letters; vol. 50; nb. 29; (2009); p. 4262 - 4264, View in Reaxys; Chimenti, Franco; Secci, Daniela; Bolasco, Adriana; Chimenti, Paola; Bizzarri, Bruna; Granese, Arianna; Carradori, Simone; Yanez, Matilde; Orallo, Francisco; Ortuso, Francesco; Alcaro, Stefano; Journal of Medicinal Chemistry; vol. 52; nb. 7; (2009); p. 1935 - 1942, View in Reaxys; Goekhan-Kelekci, Nesrin; Simsek, Oe. Oezguen; Ercan, Ayse; Yelekci, Kemal; Sahin, Z. Sibel; Isik, Samil; Ucar, Guelberk; Bilgin, A. Altan; Bioorganic and Medicinal Chemistry; vol. 17; nb. 18; (2009); p. 6761 - 6772, View in Reaxys; Chimenti, Franco; Fioravanti, Rossella; Bolasco, Adriana; Chimenti, Paola; Secci, Daniela; Rossi, Francesca; Yanez, Matilde; Orallo, Francisco; Ortuso, Francesco; Alcaro, Stefano; Journal of Medicinal Chemistry; vol. 52; nb. 9; (2009); p. 2818 - 2824, View in Reaxys; Langham, James J.; Cleves, Ann E.; Spitzer, Russell; Kirshner, Daniel; Jain, Ajay N.; Journal of Medicinal Chemistry; vol. 52; nb. 19; (2009); p. 6107 - 6125, View in Reaxys; Patent; DEKEL PHARMACEUTICALS LTD.; KINDLER, Seth; SHMULEWITZ, Ascher; WO2010/13240; (2010); (A1) English, View in Reaxys; Chimenti, Franco; Carradori, Simone; Secci, Daniela; Bolasco, Adriana; Bizzarri, Bruna; Chimenti, Paola; Granese, Arianna; Yanez, Matilde; Orallo, Francisco; European Journal of Medicinal Chemistry; vol. 45; nb. 2; (2010); p. 800 - 804, View in Reaxys; Sahoo, Anasuya; Yabanoglu, Samiye; Sinha, Barij N.; Ucar, Gulberk; Basu, Arijit; Jayaprakash, Venkatesan; Bioorganic and Medicinal Chemistry Letters; vol. 20; nb. 1; (2010); p. 132 - 136, View in Reaxys; Chimenti, Franco; Fioravanti, Rossella; Bolasco, Adriana; Chimenti, Paola; Secci, Daniela; Rossi, Francesca; Yanez, Matilde; Orallo, Francisco; Ortuso, Francesco; Alcaro, Stefano; Cirilli, Roberto; Ferretti, Rosella; Sanna, M. Luisa; Bioorganic and Medicinal Chemistry; vol. 18; nb. 3; (2010); p. 1273 - 1279, View in Reaxys; Shi, Lei; Yang, Ying; Li, Zi-Lin; Zhu, Zhen-Wei; Liu, Chang-Hong; Zhu, Hai-Liang; Bioorganic and Medicinal Chemistry; vol. 18; nb. 4; (2010); p. 1659 - 1664, View in Reaxys; Karuppasamy, Muthukumar; Mahapatra, Manojkumar; Yabanoglu, Samiye; Ucar, Gulberk; Sinha, Barij Nayan; Basu, Arijit; Mishra, Nibha; Sharon, Ashoke; Kulandaivelu, Umasankar; Jayaprakash, Venkatesan; Bioorganic and Medicinal Chemistry; vol. 18; nb. 5; (2010); p. 1875 - 1881, View in Reaxys; Varma, Manthena V. S.; Obach, R. Scott; Rotter, Charles; Miller, Howard R.; Chang, George; Steyn, Stefanus J.; El-Kattan, Ayman; Troutman, Matthew D.; Journal of Medicinal Chemistry; vol. 53; nb. 3; (2010); p. 1098 - 1108, View in Reaxys 6 of 239

Comment (Pharmacological Data)

Bioactivities present

Patent; UNIVERSIDADE DE SANTIAGO DE COMPOSTELA; SANTANA PENIN, Lourdes; ORALLO CAMBEIRO, Francisco; VINA CASTELAO, Dolores; CORREIA PINTO CARVALHO DE MATOS, Maria Joao; QUEZADA GONZALEZ, Elias Neftali; YANEZ JATO, Matilde; VILAR VARELA, Santiago; URIARTE VILARES, Eugenio; WO2010/86484; (2010); (A1) Spanish, View in Reaxys; Alcaro, Stefano; Gaspar, Alexandra; Ortuso, Francesco; Milhazes, Nuno; Orallo, Francisco; Uriarte, Eugenio; Yanez, Matilde; Borges, Fernanda; Bioorganic and Medicinal Chemistry Letters; vol. 20; nb. 9; (2010); p. 2709 - 2712, View in Reaxys; Chimenti, Franco; Secci, Daniela; Bolasco, Adriana; Chimenti, Paola; Granese, Arianna; Carradori, Simone; MacCioni, Elias; Cardia, M. Cristina; Yanez, Matilde; Orallo, Francisco; Alcaro, Stefano; Ortuso, Francesco; Cirilli, Roberto; Ferretti, Rosella; Distinto, Simona; Kirchmair, Johannes; Langer, Thierry; Bioorganic and Medicinal Chemistry; vol. 18; nb. 14;

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Comment (Pharmacological Data)

Bioactivities present

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Bioactivities present

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Comment (Pharmacological Data)

Bioactivities present

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Comment (Pharmacological Data)

Bioactivities present

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Comment (Pharmacological Data)

Bioactivities present

Neta, Pedatsur; Farahani, Mahnaz; Simn-Manso, Yamil; Liang, Yuxue; Yang, Xiaoyu; Stein, Stephen E.; Rapid Communications in Mass Spectrometry; vol. 28; nb. 23; (2014); p. 2645 - 2660, View in Reaxys; Turkmenoglu, Fatma Pinar; Baysal, Ipek; Ciftci-Yabanoglu, Samiye; Yelekci, Kemal; Temel, Hamdi; Paa, Salih; Ezer, Nurten; ali, Ihsan; Ucar, Gulberk; Molecules; vol. 20; nb. 5; (2015); p. 7454 - 7473, View in Reaxys; Gockel, Samuel N.; Hull, Kami L.; Organic Letters; vol. 17; nb. 13; (2015); p. 3236 - 3239, View in Reaxys; Thriault, Olivier; Poulin, Hugo; Beaulieu, Jean-Martin; Chahine, Mohamed; European Journal of Pharmacology; vol. 764; (2015); p. 395 - 403, View in Reaxys; Mathew, Bijo; Mathew, Githa Elizabeth; Uar, Gülberk; Baysal, Ipek; Suresh, Jerad; Vilapurathu, Jobin Kunjumon; Prakasan, Aneesh; Suresh, Jeethu Kuruppath; Thomas, Anjana; Bioorganic Chemistry; vol. 62; (2015); p. 22 - 29, View in Reaxys; Vaikkinen, Anu; Shrestha, Bindesh; Koivisto, Juha; Kostiainen, Risto; Vertes, Akos; Kauppila, Tiina J.; Rapid Communications in Mass Spectrometry; vol. 28; nb. 23; (2014); p. 2490 - 2496, View in Reaxys; Evranos-Aksöz, Begüm; Baysal, Ipek; Yabanolu-ifti, Samiye; Djikic, Teodora; Yeleki, Kemal; Uar, Gülberk; Ertan, Rahmiye; Archiv der Pharmazie; vol. 348; nb. 10; (2015); p. 743 - 756, View in Reaxys; Hacker, Kristina; Maas, Renke; Kornhuber, Johannes; Fromm, Martin F.; Zolk, Oliver; PLoS ONE; vol. 10; nb. 9; (2015); Art.No: E0136451, View in Reaxys; Mathew, Bijo; Uar, Gülberk; Yabanogclu-ifti, Samiye; Baysal, Ipek; Suresh, Jerad; Mathew, Githa Elizabeth; Vilapurathu, Jobin Kunjumon; Nadeena; Nabeela; Lakshmi; Haridas, Abitha; Fathima, Fajeelath; Letters in Organic Chemistry; vol. 12; nb. 9; (2015); p. 605 613, View in Reaxys; Suthar, Sharad Kumar; Bansal, Sumit; Alam, Md. Maqusood; Jaiswal, Varun; Tiwari, Amit; Chaudhary, Anil; Alex, Angel Treasa; Joseph, Alex; Bioorganic and Medicinal Chemistry Letters; vol. 25; nb. 22; (2015); p. 5281 - 5285, View in Reaxys; D'Ascenzio, Melissa; Chimenti, Paola; Gidaro, Maria Concetta; De Monte, Celeste; De Vita, Daniela; Granese, Arianna; Scipione, Luigi; Di Santo, Roberto; Costa, Giosu; Alcaro, Stefano; Yez, Matilde; Carradori, Simone; Journal of Enzyme Inhibition and Medicinal Chemistry; vol. 30; nb. 6; (2015); p. 908 - 919, View in Reaxys; Distinto, Simona; Meleddu, Rita; Yanez, Matilde; Cirilli, Roberto; Bianco, Giulia; Sanna, Maria Luisa; Arridu, Antonella; Cossu, Pietro; Cottiglia, Filippo; Faggi, Cristina; Ortuso, Francesco; Alcaro, Stefano; Maccioni, Elias; European Journal of Medicinal Chemistry; vol. 108; (2016); p. 542 - 552, View in Reaxys; Badavath, Vishnu N.; Baysal, Ipek; Uar, Gülberk; Mondal, Susanta K.; Sinha, Barij N.; Jayaprakash, Venkatesan; Archiv der Pharmazie; vol. 349; nb. 1; (2016); p. 9 - 19, View in Reaxys; Badavath, Vishnu Nayak; Baysal, Ipek; Ucar, Gulberk; Sinha, Barij Nayan; Jayaprakash, Venkatesan; ACS Medicinal Chemistry Letters; vol. 7; nb. 1; (2016); p. 56 - 61, View in Reaxys; Goldstein, David S.; Jinsmaa, Yunden; Sullivan, Patti; Holmes, Courtney; Kopin, Irwin J.; Sharabi, Yehonatan; Journal of Pharmacology and Experimental Therapeutics; vol. 356; nb. 2; (2016); p. 483 - 492, View in Reaxys; Iqbal, Naeem; Cho, Eun Jin; Journal of Organic Chemistry; vol. 81; nb. 5; (2016); p. 1905 - 1911, View in Reaxys; Desideri, Nicoletta; Proietti Monaco, Luca; Fioravanti, Rossella; Biava, Mariangela; Yez, Matilde; Alcaro, Stefano; Ortuso, Francesco; European Journal of Medicinal Chemistry; vol. 117; (2016); p. 292 - 300, View in Reaxys; Ulferts, Rachel; De Boer, S. Matthijn; Van

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Der Linden, Lonneke; Bauer, Lisa; Lyoo, Hey Rhyoung; Maté, Maria J.; Lichière, Julie; Canard, Bruno; Lelieveld, Daphne; Omta, Wienand; Egan, David; Coutard, Bruno; Van Kuppeveld, Frank J. M.; Antimicrobial Agents and Chemotherapy; vol. 60; nb. 5; (2016); p. 2627 - 2638, View in Reaxys; Estrada, Martín; Herrera-Arozamena, Clara; Pérez, Concepción; Viña, Dolores; Romero, Alejandro; Morales-García, José A.; Pérez-Castillo, Ana; Rodríguez-Franco, María Isabel; European Journal of Medicinal Chemistry; vol. 121; (2016); p. 376 - 386, View in Reaxys; Choi, Stephanie K. Y.; Boyle, Eleanor; Cairney, John; Gardner, Sandra; Collins, Evan J.; Bacon, Jean; Rourke, Sean B.; Burchell, Ann N.; Rueda, Sergio; Bayoumi, Ahmed; Gough, Kevin; Cohen, Jeffrey; Cooper, Curtis; Kilby, Don; Loutfy, Mona; Crouzat, Fred; Rachlis, Anita; Mittmann, Nicole; Raboud, Janet; Salit, Irving; Ralph, Edward; Sandre, Roger; Evans, Gerald; Wobeser, Wendy; PLoS ONE; vol. 11; nb. 6; (2016); Art.No: E0156652, View in Reaxys 12 of 239

Comment (Pharmacological Data)

Bioactivities present

Mathew, Bijo; Haridas, Abitha; Lakshmanan, Baskar; Uar, Gülberk; Baysal, Ipek; Joy, Monu; Mathew, Githa E.; Jayaprakash, Venkatesan; ChemMedChem; (2016); p. 1161 - 1171, View in Reaxys 13 of 239

Comment (Pharmacological Data)

physiological behaviour discussed

Fioravanti, Rossella; Desideri, Nicoletta; Biava, Mariangela; Proietti Monaco, Luca; Grammatica, Laura; Yanez, Matilde; Bioorganic and Medicinal Chemistry Letters; vol. 23; nb. 18; (2013); p. 5128 - 5130, View in Reaxys; D'Ascenzio, Melissa; Carradori, Simone; Secci, Daniela; Mannina, Luisa; Sobolev, Anatoly P.; De Monte, Celeste; Cirilli, Roberto; Yanez, Matilde; Alcaro, Stefano; Ortuso, Francesco; Bioorganic and Medicinal Chemistry; vol. 22; nb. 10; (2014); p. 2887 - 2895, View in Reaxys; Distinto, Simona; Meleddu, Rita; Yanez, Matilde; Cirilli, Roberto; Bianco, Giulia; Sanna, Maria Luisa; Arridu, Antonella; Cossu, Pietro; Cottiglia, Filippo; Faggi, Cristina; Ortuso, Francesco; Alcaro, Stefano; Maccioni, Elias; European Journal of Medicinal Chemistry; vol. 108; (2016); p. 542 - 552, View in Reaxys 14 of 239

Comment (Pharmacological Data)

physiological behaviour discussed

Delogu, Giovanna L.; Serra, Silvia; Quezada, Elias; Uriarte, Eugenio; Vilar, Santiago; Tatonetti, Nicholas P.; Vina, Dolores; ChemMedChem; vol. 9; nb. 8; (2014); p. 1672 - 1676, View in Reaxys; Badavath, Vishnu Nayak; Ciftci-Yabanoglu; Bhakat, Soumendranath; Timiri, Ajay Kumar; Sinha, Barij N.; Ucar; Soliman, Mahmoud E.S.; Jayaprakash, Venkatesan; Bioorganic Chemistry; vol. 58; (2014); p. 72 - 80, View in Reaxys; Mathew, Bijo; Mathew, Githa Elizabeth; Uar, Gülberk; Baysal, Ipek; Suresh, Jerad; Vilapurathu, Jobin Kunjumon; Prakasan, Aneesh; Suresh, Jeethu Kuruppath; Thomas, Anjana; Bioorganic Chemistry; vol. 62; (2015); p. 22 - 29, View in Reaxys; Goldstein, David S.; Jinsmaa, Yunden; Sullivan, Patti; Holmes, Courtney; Kopin, Irwin J.; Sharabi, Yehonatan; Journal of Pharmacology and Experimental Therapeutics; vol. 356; nb. 2; (2016); p. 483 - 492, View in Reaxys 15 of 239

Comment (Pharmacological Data)

physiological behaviour discussed

Badavath, Vishnu N.; Baysal, Ipek; Uar, Gülberk; Mondal, Susanta K.; Sinha, Barij N.; Jayaprakash, Venkatesan; Archiv der Pharmazie; vol. 349; nb. 1; (2016); p. 9 - 19, View in Reaxys 16 of 239

Comment (Pharmacological Data)

physiological behaviour discussed

Badavath, Vishnu Nayak; Baysal, Ipek; Ucar, Gulberk; Sinha, Barij Nayan; Jayaprakash, Venkatesan; ACS Medicinal Chemistry Letters; vol. 7; nb. 1; (2016); p. 56 - 61, View in Reaxys 17 of 239

Comment (Pharmacological Data)

physiological behaviour discussed

Desideri, Nicoletta; Proietti Monaco, Luca; Fioravanti, Rossella; Biava, Mariangela; Yez, Matilde; Alcaro, Stefano; Ortuso, Francesco; European Journal of Medicinal Chemistry; vol. 117; (2016); p. 292 - 300, View in Reaxys 18 of 239

Comment (Pharmacological Data)

physiological behaviour discussed

Estrada, Martín; Herrera-Arozamena, Clara; Pérez, Concepción; Viña, Dolores; Romero, Alejandro; MoralesGarcía, José A.; Pérez-Castillo, Ana; Rodríguez-Franco, María Isabel; European Journal of Medicinal Chemistry; vol. 121; (2016); p. 376 - 386, View in Reaxys 19 of 239

Comment (Pharmacological Data)

physiological behaviour discussed

Mathew, Bijo; Haridas, Abitha; Lakshmanan, Baskar; Uar, Gülberk; Baysal, Ipek; Joy, Monu; Mathew, Githa E.; Jayaprakash, Venkatesan; ChemMedChem; (2016); p. 1161 - 1171, View in Reaxys 20 of 239

Comment (Pharmacological Data)

physiological behaviour discussed

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Nayak, Badavath Vishnu; Ciftci-Yabanoglu; Bhakat, Soumendranath; Timiri, Ajay Kumar; Sinha, Barij N.; Ucar; Soliman, Mahmoud E. S.; Jayaprakash, Venkatesan; Bioorganic Chemistry; vol. 58; (2015); p. 72 - 80, View in Reaxys 21 of 239

Comment (Pharmacological Data)

physiological behaviour discussed

Comment (Pharmacological Data)

physiological behaviour discussed

Patent; THE UNIVERSITY OF BRITISH COLUMBIA; CENTRE FOR DRUG RESEARCH AND DEVELOPMENT; PUTNINS, Edward Ewald; GRIERSON, David Scott; GEALAGEAS, Ronan F., B.; DEVINEAU, Alice Andree Valentine; DULLAGHAN, Edith Mary; WO2015/27324; (2015); (A1) English, View in Reaxys 23 of 239

Comment (Pharmacological Data)

physiological behaviour discussed

Khattab, Sherine N.; Abdel Moneim, Shimaa A. H.; Bekhit, Adnan A.; El Massry, Abdel Moneim; Hassan, Seham Y.; El-Faham, Ayman; Ali Ahmed, Hany Emary; Amer, Adel; European Journal of Medicinal Chemistry; vol. 93; (2015); p. 308 - 320, View in Reaxys 24 of 239

Comment (Pharmacological Data)

physiological behaviour discussed

Thriault, Olivier; Poulin, Hugo; Beaulieu, Jean-Martin; Chahine, Mohamed; European Journal of Pharmacology; vol. 764; (2015); p. 395 - 403, View in Reaxys 25 of 239

Comment (Pharmacological Data)

physiological behaviour discussed

Nirogi, Ramakrishna; Palacharla, Raghava Choudary; Mohammed, Abdul Rasheed; Manoharan, Arunkumar; Ponnamaneni, Ranjith Kumar; Bhyrapuneni, Gopinadh; Chemico-Biological Interactions; vol. 230; (2015); p. 9 20, View in Reaxys 26 of 239

Comment (Pharmacological Data)

physiological behaviour discussed

Turkmenoglu, Fatma Pinar; Baysal, Ipek; Ciftci-Yabanoglu, Samiye; Yelekci, Kemal; Temel, Hamdi; Paa, Salih; Ezer, Nurten; ali, Ihsan; Ucar, Gulberk; Molecules; vol. 20; nb. 5; (2015); p. 7454 - 7473, View in Reaxys 27 of 239

Comment (Pharmacological Data)

physiological behaviour discussed

Evranos-Aksöz, Begüm; Baysal, Ipek; Yabanolu-ifti, Samiye; Djikic, Teodora; Yeleki, Kemal; Uar, Gülberk; Ertan, Rahmiye; Archiv der Pharmazie; vol. 348; nb. 10; (2015); p. 743 - 756, View in Reaxys 28 of 239

Comment (Pharmacological Data)

physiological behaviour discussed

Mathew, Bijo; Uar, Gülberk; Yabanogclu-ifti, Samiye; Baysal, Ipek; Suresh, Jerad; Mathew, Githa Elizabeth; Vilapurathu, Jobin Kunjumon; Nadeena; Nabeela; Lakshmi; Haridas, Abitha; Fathima, Fajeelath; Letters in Organic Chemistry; vol. 12; nb. 9; (2015); p. 605 - 613, View in Reaxys 29 of 239

Comment (Pharmacological Data)

physiological behaviour discussed

Suthar, Sharad Kumar; Bansal, Sumit; Alam, Md. Maqusood; Jaiswal, Varun; Tiwari, Amit; Chaudhary, Anil; Alex, Angel Treasa; Joseph, Alex; Bioorganic and Medicinal Chemistry Letters; vol. 25; nb. 22; (2015); p. 5281 5285, View in Reaxys 30 of 239

Comment (Pharmacological Data)

physiological behaviour discussed

D'Ascenzio, Melissa; Chimenti, Paola; Gidaro, Maria Concetta; De Monte, Celeste; De Vita, Daniela; Granese, Arianna; Scipione, Luigi; Di Santo, Roberto; Costa, Giosu; Alcaro, Stefano; Yez, Matilde; Carradori, Simone; Journal of Enzyme Inhibition and Medicinal Chemistry; vol. 30; nb. 6; (2015); p. 908 - 919, View in Reaxys 31 of 239

Comment (Pharmacological Data)

physiological behaviour discussed

Mattsson, Cecilia; Svensson, Peder; Sonesson, Clas; European Journal of Medicinal Chemistry; vol. 73; (2014); p. 177 - 186, View in Reaxys

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32 of 239

Comment (Pharmacological Data)

physiological behaviour discussed

Evranos-Aksoez, Beguem; Yabanoglu-Ciftci, Samiye; Ucar, Guelberk; Yelekci, Kemal; Ertan, Rahmiye; Bioorganic and Medicinal Chemistry Letters; vol. 24; nb. 15; (2014); p. 3278 - 3284, View in Reaxys 33 of 239

Comment (Pharmacological Data)

physiological behaviour discussed

Poirier, Agnes; Cascais, Anne-Christine; Bader, Urs; Portmann, Renee; Brun, Marie-Elise; Walter, Isabelle; Hillebrecht, Alexander; Ullah, Mohammed; Funk, Christoph; Drug Metabolism and Disposition; vol. 42; nb. 9; (2014); p. 1411 - 1422, View in Reaxys 34 of 239

Comment (Pharmacological Data)

physiological behaviour discussed

Bautista-Aguilera, Oscar M.; Samadi, Abdelouahid; Chioua, Mourad; Nikolic, Katarina; Filipic, Slavica; Agbaba, Danica; Soriano, Elena; De Andrs, Luca; Rodrguez-Franco, Mara Isabel; Alcaro, Stefano; Ramsay, Rona R.; Ortuso, Francesco; Yaez, Matilde; Marco-Contelles, Jos; Journal of Medicinal Chemistry; vol. 57; nb. 24; (2014); p. 10455 - 10463, View in Reaxys 35 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

brain mitochondrial suspension of Sprague-Dawley rat

Sex

male

Kind of Dosing (Pharmacological Data)

comparative comp. dissolved in DMSO

Method (Pharmacological Data)

name of assay/method: continuous spectrophotometric assay

Further Details (Pharmacological Data)

inhibitory concentration (IC); IC50 related to: MAO-A

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

10000 nmol/l

Pisani, Leonardo; Barletta, Maria; Soto-Otero, Ramon; Nicolotti, Orazio; Mendez-Alvarez, Estefania; Catto, Marco; Introcaso, Antonellina; Stefanachi, Angela; Cellamare, Saverio; Altomare, Cosimo; Carotti, Angelo; Journal of Medicinal Chemistry; vol. 56; nb. 6; (2013); p. 2651 - 2664, View in Reaxys 36 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

brain mitochondrial suspension of Sprague-Dawley rat

Sex

male

Kind of Dosing (Pharmacological Data)

comparative comp. dissolved in DMSO

Method (Pharmacological Data)

name of assay/method: continuous spectrophotometric assay

Results

molecular target: MAO-A; species of target: rat

Comment (Pharmacological Data)

physiological behaviour discussed

Comment (Pharmacological Data)

physiological behaviour discussed

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Comment (Pharmacological Data)

physiological behaviour discussed

Comment (Pharmacological Data)

physiological behaviour discussed

Gocmez, Semil Selcen; Utkan, Tijen; Gacar, Nejat; European Journal of Pharmacology; vol. 714; nb. 1-3; (2013); p. 442 - 447, View in Reaxys 41 of 239

Effect (Pharmacological Data)

neurotransmitter levels; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

37 μmol/kg

Kind of Dosing (Pharmacological Data)

comparative comp. dissolved in 0.9percent w/v of physiological saline

Further Details (Pharmacological Data)

microdialysis; DOPAC: 3,4-dihydroxyphenylacetic acid; MT: methoxytyramine; mass of species: 220 - 270 g

Results

molecular target: rat monoamine oxidase A (physiological molecular target)

Location

supporting information

Pettersson, Fredrik; Svensson, Peder; Waters, Susanna; Waters, Nicholas; Sonesson, Clas; Journal of Medicinal Chemistry; vol. 55; nb. 7; (2012); p. 3242 - 3249, View in Reaxys 42 of 239

Effect (Pharmacological Data)

neurotransmitter levels; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

37 μmol/kg

Kind of Dosing (Pharmacological Data)

comparative comp. dissolved in 0.9percent w/v of physiological saline

Further Details (Pharmacological Data)

microdialysis; DOPAC: 3,4-dihydroxyphenylacetic acid; MT: methoxytyramine; mass of species: 220 - 270 g; 3-MT level rate related to: striatum, brain

Type (Pharmacological Data)

3-MT level rate

Value of Type (Pharmacological Data)

400 percent

Location

supporting information

Pettersson, Fredrik; Svensson, Peder; Waters, Susanna; Waters, Nicholas; Sonesson, Clas; Journal of Medicinal Chemistry; vol. 55; nb. 7; (2012); p. 3242 - 3249, View in Reaxys 43 of 239

Effect (Pharmacological Data)

neurotransmitter levels; effect on

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

subcutaneous

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Concentration (Pharmacological Data)

37 μmol/kg

Kind of Dosing (Pharmacological Data)

comparative comp. dissolved in 0.9percent w/v of physiological saline

Further Details (Pharmacological Data)

microdialysis; DOPAC: 3,4-dihydroxyphenylacetic acid; MT: methoxytyramine; mass of species: 220 - 270 g; DOPAC level rate related to: striatum, brain

Type (Pharmacological Data)

DOPAC level rate

Value of Type (Pharmacological Data)

18 percent

Location

supporting information

Pettersson, Fredrik; Svensson, Peder; Waters, Susanna; Waters, Nicholas; Sonesson, Clas; Journal of Medicinal Chemistry; vol. 55; nb. 7; (2012); p. 3242 - 3249, View in Reaxys 44 of 239

Effect (Pharmacological Data)

OATP1B1-mediated E17βG uptake; inhibition of

Species or Test-System (Pharmacological Data)

HEK293 Flp-In cells; genetically modified/infected with: human OATP1B1-pcDNA5/FRT

Concentration (Pharmacological Data)

20 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. dissolved in DMSO

Further Details (Pharmacological Data)

OATP1B1 (SLCO1B1): organic anion transporting polypeptide 1B1 transporter; HEK: human embryonic kidney; substrate: E17βG (estradiol-17β-glucuronide, 0.52 μmol/l); singlepoint assay

Results

molecular target: human OATP1B1

Location

supporting information

Karlgren, Maria; Vildhede, Anna; Norinder, Ulf; Wisniewski, Jacek R.; Kimoto, Emi; Lai, Yurong; Haglund, Ulf; Artursson, Per; Journal of Medicinal Chemistry; vol. 55; nb. 10; (2012); p. 4740 - 4763, View in Reaxys 45 of 239

Effect (Pharmacological Data)

OATP1B1-mediated E17βG uptake; inhibition of

Species or Test-System (Pharmacological Data)

HEK293 Flp-In cells; genetically modified/infected with: human OATP1B1-pcDNA5/FRT

Concentration (Pharmacological Data)

20 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. dissolved in DMSO

Further Details (Pharmacological Data)

OATP1B1 (SLCO1B1): organic anion transporting polypeptide 1B1 transporter; HEK: human embryonic kidney; substrate: E17βG (estradiol-17β-glucuronide, 0.52 μmol/l); singlepoint assay; inhibition rate related to: OATP1B1

Type (Pharmacological Data)

inhibition rate

Value of Type (Pharmacological Data)

1.7 percent

Location

supporting information

Effect (Pharmacological Data)

OATP1B3-mediated E17βG uptake; stimulation of

Species or Test-System (Pharmacological Data)

HEK293 Flp-In cells; genetically modified/infected with: human OATP1B3-pcDNA5/FRT

Concentration (Pharmacological Data)

20 μmol/l

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Kind of Dosing (Pharmacological Data)

title comp. dissolved in DMSO

Further Details (Pharmacological Data)

OATP1B3 (SLCO1B3): organic anion transporting polypeptide 1B3 transporter; HEK: human embryonic kidney; substrate: E17βG (estradiol-17β-glucuronide, 1.04 μmol/l); singlepoint assay

Results

molecular target: human OATP1B3

Location

supporting information

Effect (Pharmacological Data)

OATP1B3-mediated E17βG uptake; stimulation of

Species or Test-System (Pharmacological Data)

HEK293 Flp-In cells; genetically modified/infected with: human OATP1B3-pcDNA5/FRT

Concentration (Pharmacological Data)

20 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. dissolved in DMSO

Further Details (Pharmacological Data)

OATP1B3 (SLCO1B3): organic anion transporting polypeptide 1B3 transporter; HEK: human embryonic kidney; substrate: E17βG (estradiol-17β-glucuronide, 1.04 μmol/l); singlepoint assay; stimulation rate related to: OATP1B3

Type (Pharmacological Data)

stimulation rate

Value of Type (Pharmacological Data)

3.3 percent

Location

supporting information

Effect (Pharmacological Data)

OATP2B1-mediated E3S uptake; inhibition of

Species or Test-System (Pharmacological Data)

HEK293 Flp-In cells; genetically modified/infected with: human OATP2B1-pcDNA5/FRT

Concentration (Pharmacological Data)

20 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. dissolved in DMSO

Further Details (Pharmacological Data)

OATP2B1 (SLCO2B1): organic anion transporting polypeptide 2B1 transporter; HEK: human embryonic kidney; substrate: E3S (estrone-3-sulfate, 1.02 μmol/l); single-point assay

Results

molecular target: human OATP2B1

Location

supporting information

Effect (Pharmacological Data)

OATP2B1-mediated E3S uptake; inhibition of

Species or Test-System (Pharmacological Data)

HEK293 Flp-In cells; genetically modified/infected with: human OATP2B1-pcDNA5/FRT

Concentration (Pharmacological Data)

20 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. dissolved in DMSO

Further Details (Pharmacological Data)

OATP2B1 (SLCO2B1): organic anion transporting polypeptide 2B1 transporter; HEK: human embryonic kidney; substrate: E3S (estrone-3-sulfate, 1.02 μmol/l); single-point assay; inhibition rate related to: OATP2B1

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Type (Pharmacological Data)

inhibition rate

Value of Type (Pharmacological Data)

27.5 percent

Location

supporting information

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

monoamine oxidase A

Concentration (Pharmacological Data)

70 μmol/l

Further Details (Pharmacological Data)

spectrofluorometry

Results

molecular target: monoamine oxidase A

Location

supporting information

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

monoamine oxidase A

Concentration (Pharmacological Data)

70 μmol/l

Further Details (Pharmacological Data)

spectrofluorometry

Type (Pharmacological Data)

inhibition rate

Value of Type (Pharmacological Data)

50 percent

Location

supporting information

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

monoamine oxidase B

Concentration (Pharmacological Data)

70 μmol/l

Further Details (Pharmacological Data)

spectrofluorometry

Results

molecular target: monoamine oxidase B

Location

supporting information

Effect (Pharmacological Data)

enzyme activity; inhibition of

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Species or Test-System (Pharmacological Data)

monoamine oxidase B

Concentration (Pharmacological Data)

70 μmol/l

Further Details (Pharmacological Data)

spectrofluorometry

Type (Pharmacological Data)

inhibition rate

Value of Type (Pharmacological Data)

20 percent

Location

supporting information

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

recombinant mono amine oxidase-A of human

Further Details (Pharmacological Data)

inhibition constant (Ki)

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

0.005 μmol/l

Sentuerk, Kerem; Tan, Oya Unsal; Ciftci, Samiye Yabanoglu; Ucar, Guelberk; Palaska, Erhan; Archiv der Pharmazie; vol. 345; nb. 9; (2012); p. 695 - 702, View in Reaxys 55 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

recombinant mono amine oxidase-A of human

Results

molecular target: mono amine oxidase-A; species of target: human

Sentuerk, Kerem; Tan, Oya Unsal; Ciftci, Samiye Yabanoglu; Ucar, Guelberk; Palaska, Erhan; Archiv der Pharmazie; vol. 345; nb. 9; (2012); p. 695 - 702, View in Reaxys 56 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

recombinant mono amine oxidase-B of human

Further Details (Pharmacological Data)

inhibition constant (Ki)

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

1.22 μmol/l

Sentuerk, Kerem; Tan, Oya Unsal; Ciftci, Samiye Yabanoglu; Ucar, Guelberk; Palaska, Erhan; Archiv der Pharmazie; vol. 345; nb. 9; (2012); p. 695 - 702, View in Reaxys 57 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

recombinant mono amine oxidase-B of human

Results

molecular target: mono amine oxidase-B; species of target: human

Sentuerk, Kerem; Tan, Oya Unsal; Ciftci, Samiye Yabanoglu; Ucar, Guelberk; Palaska, Erhan; Archiv der Pharmazie; vol. 345; nb. 9; (2012); p. 695 - 702, View in Reaxys

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58 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

monoamine oxidase-B of human

Method (Pharmacological Data)

name of assay/method: fluorometric method

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

361.38 μmol/l

Secci, Daniela; Bolasco, Adriana; Carradori, Simone; D'Ascenzio, Melissa; Nescatelli, Riccardo; Yanez, Matilde; European Journal of Medicinal Chemistry; vol. 58; (2012); p. 405 - 417, View in Reaxys 59 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

calf mitochondria

Kind of Dosing (Pharmacological Data)

comparative comp. dissolved in DMSO

Method (Pharmacological Data)

name of assay/method: fluorometric assay

Further Details (Pharmacological Data)

Ki related to: monoamine oxidase A

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

11.5 μmol/l

Abdelhafez, Omaima M.; Amin, Kamelia M.; Ali, Hamed I.; Abdalla, Mohamed M.; Batran, Rasha Z.; Journal of Medicinal Chemistry; vol. 55; nb. 23; (2012); p. 10424 - 10436, View in Reaxys 60 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

calf mitochondria

Kind of Dosing (Pharmacological Data)

comparative comp. dissolved in DMSO

Method (Pharmacological Data)

name of assay/method: fluorometric assay

Further Details (Pharmacological Data)

Ki related to: monoamine oxidase B

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

> 100 μmol/l

Abdelhafez, Omaima M.; Amin, Kamelia M.; Ali, Hamed I.; Abdalla, Mohamed M.; Batran, Rasha Z.; Journal of Medicinal Chemistry; vol. 55; nb. 23; (2012); p. 10424 - 10436, View in Reaxys 61 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

calf mitochondria

Kind of Dosing (Pharmacological Data)

comparative comp. dissolved in DMSO

Method (Pharmacological Data)

name of assay/method: fluorometric assay

Results

molecular target: monoamine oxidase A

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Abdelhafez, Omaima M.; Amin, Kamelia M.; Ali, Hamed I.; Abdalla, Mohamed M.; Batran, Rasha Z.; Journal of Medicinal Chemistry; vol. 55; nb. 23; (2012); p. 10424 - 10436, View in Reaxys 62 of 239

Effect (Pharmacological Data)

5-HIAA levels; decrease of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Concentration (Pharmacological Data)

37 μmol/kg

Kind of Dosing (Pharmacological Data)

comparative comp. dissolved in physiological saline 0.9percent w/v NaCl

Method (Pharmacological Data)

name of assay/method: post-mortem neurochemistry analysis

Further Details (Pharmacological Data)

percent of control related to: striatum

Type (Pharmacological Data)

percent of control

Value of Type (Pharmacological Data)

81 percent

Mattsson, Cecilia; Andreasson, Theresa; Waters, Nicholas; Sonesson, Clas; Journal of Medicinal Chemistry; vol. 55; nb. 22; (2012); p. 9735 - 9750, View in Reaxys 63 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

monoamine oxidase A of human

Further Details (Pharmacological Data)

inhibitory concentration (IC)

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

361 μmol/l

Santana, Lourdes; Gonzalez-Diaz, Humberto; Quezada, Elias; Uriarte, Eugenio; Yanez, Matilde; Vina, Dolores; Orallo, Francisco; Journal of Medicinal Chemistry; vol. 51; nb. 21; (2008); p. 6740 - 6751, View in Reaxys; Desideri, Nicoletta; Bolasco, Adriana; Fioravanti, Rossella; Proietti Monaco, Luca; Orallo, Francisco; Yanez, Matilde; Ortuso, Francesco; Alcaro, Stefano; Journal of Medicinal Chemistry; vol. 54; nb. 7; (2011); p. 2155 2164, View in Reaxys 64 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

monoamine oxidase A of human

Results

molecular target: human monoamine oxidase A

Desideri, Nicoletta; Bolasco, Adriana; Fioravanti, Rossella; Proietti Monaco, Luca; Orallo, Francisco; Yanez, Matilde; Ortuso, Francesco; Alcaro, Stefano; Journal of Medicinal Chemistry; vol. 54; nb. 7; (2011); p. 2155 2164, View in Reaxys 65 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

BTI insect cells; genetically modified/infected with: baculovirus, recombinant human monoamine oxidase A

Further Details (Pharmacological Data)

Ki related to: human monoamine oxidase A

Type (Pharmacological Data)

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Value of Type (Pharmacological Data)

0.005 μmol/l

Jagrat, Monika; Behera, Jagannath; Yabanoglu, Samiye; Ercan, Ayse; Ucar, Gulberk; Sinha, Barij Nayan; Sankaran, Vadivelan; Basu, Arijit; Jayaprakash, Venkatesan; Bioorganic and Medicinal Chemistry Letters; vol. 21; nb. 14; (2011); p. 4296 - 4300, View in Reaxys 66 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

BTI insect cells; genetically modified/infected with: baculovirus, recombinant human monoamine oxidase A

Results

molecular target: human monoamine oxidase A

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

BTI insect cells; genetically modified/infected with: baculovirus, recombinant human monoamine oxidase B

Further Details (Pharmacological Data)

Ki related to: human monoamine oxidase B

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

1.08 μmol/l

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

BTI insect cells; genetically modified/infected with: baculovirus, recombinant human monoamine oxidase B

Results

molecular target: human monoamine oxidase B

Effect (Pharmacological Data)

transporter; inhibition of

Species or Test-System (Pharmacological Data)

HEK293-Flp-In cells; genetically modified/infected with: human OCT2

Concentration (Pharmacological Data)

20 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. dissolved in DMSO

Further Details (Pharmacological Data)

OCT2: organic cation transporter 2 (solute carrier 22A2); HEK: human embryonic kidney; fluorescent probe substrate: 4-(4-(dimethylamino)styryl)-N-methyl-pyridinium (ASP+) (5 μmol/l); high-throughput assay; fluorimetry; inhibition rate related to: OCT2

Type (Pharmacological Data)

inhibition rate

Value of Type (Pharmacological Data)

25.3 percent

Location

supporting information

Kido, Yasuto; Matsson, Paer; Giacomini, Kathleen M.; Journal of Medicinal Chemistry; vol. 54; nb. 13; (2011); p. 4548 - 4558, View in Reaxys

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Effect (Pharmacological Data)

transporter; inhibition of

Species or Test-System (Pharmacological Data)

HEK293-Flp-In cells; genetically modified/infected with: human OCT2

Concentration (Pharmacological Data)

20 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. dissolved in DMSO

Further Details (Pharmacological Data)

Results

molecular target: human OCT2

Location

supporting information

Kido, Yasuto; Matsson, Paer; Giacomini, Kathleen M.; Journal of Medicinal Chemistry; vol. 54; nb. 13; (2011); p. 4548 - 4558, View in Reaxys 71 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

recombinant microsomal monoamine oxidase A of human

Kind of Dosing (Pharmacological Data)

comparative compound dissolved in deionized water

Further Details (Pharmacological Data)

Amplex Red monoamine oxidase assay; inhibitory concentration (IC)

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

361.38 μmol/l

Location

supporting information

Secci, Daniela; Carradori, Simone; Bolasco, Adriana; Chimenti, Paola; Yanez, Matilde; Ortuso, Francesco; Alcaro, Stefano; European Journal of Medicinal Chemistry; vol. 46; nb. 10; (2011); p. 4846 - 4852, View in Reaxys 72 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

recombinant microsomal monoamine oxidase A of human

Kind of Dosing (Pharmacological Data)

comparative compound dissolved in deionized water

Further Details (Pharmacological Data)

Amplex Red monoamine oxidase assay

Results

molecular target: human monoamine oxidase A

Location

supporting information

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

recombinant microsomal monoamine oxidase B of human

Kind of Dosing (Pharmacological Data)

comparative compound dissolved in deionized water

Further Details (Pharmacological Data)

Amplex Red monoamine oxidase assay; inhibitory concentration (IC)

Type (Pharmacological Data)

IC50

30/94

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Value of Type (Pharmacological Data)

7.54 μmol/l

Location

supporting information

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

recombinant microsomal monoamine oxidase B of human

Kind of Dosing (Pharmacological Data)

comparative compound dissolved in deionized water

Further Details (Pharmacological Data)

Amplex Red monoamine oxidase assay

Results

molecular target: human monoamine oxidase B

Location

supporting information

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

insect BTI-TN-5B1-4 microsomes; genetically modified/infected with: recombinant human MAO-B

Concentration (Pharmacological Data)

1 mmol/l

Further Details (Pharmacological Data)

MAO-B: monoamine oxidase B; Amplex.(R). Red MAO assay; Amplex.(R). Red: 10-acetyl-2,7-dihydroxyphenoxazine

Results

no effect (related to human MAO-B)

Prado-Prado, Francisco; Garcia-Mera, Xerardo; Escobar, Manuel; Sobarzo-Sanchez, Eduardo; Yanez, Matilde; Riera-Fernandez, Pablo; Gonzalez-Diaz, Humberto; European Journal of Medicinal Chemistry; vol. 46; nb. 12; (2011); p. 5838 - 5851, View in Reaxys 76 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

insect BTI-TN-5B1-4 microsomes; genetically modified/infected with: recombinant human MAO-A

Further Details (Pharmacological Data)

MAO-A: monoamine oxidase A; Amplex.(R). Red MAO assay; Amplex.(R). Red: 10-acetyl-2,7-dihydroxyphenoxazine; IC50 related to: human MAO-A; inhibitory concentration (IC)

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

361.38 μmol/l

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

insect BTI-TN-5B1-4 microsomes; genetically modified/infected with: recombinant human MAO-A

Further Details (Pharmacological Data)

MAO-A: monoamine oxidase A; Amplex.(R). Red MAO assay; Amplex.(R). Red: 10-acetyl-2,7-dihydroxyphenoxazine

Results

molecular target: human MAO-A

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Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

liver homogenate of rat

Further Details (Pharmacological Data)

inhibition constant (Ki); Ki related to: monoamine oxidase A

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

0.005 μmol/l

Location

supporting information

Sahoo, Anasuya; Yabanoglu, Samiye; Sinha, Barij N.; Ucar, Gulberk; Basu, Arijit; Jayaprakash, Venkatesan; Bioorganic and Medicinal Chemistry Letters; vol. 20; nb. 1; (2010); p. 132 - 136, View in Reaxys 79 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

liver homogenate of rat

Results

molecular target: monoamine oxidase A

Location

supporting information

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

liver homogenate of rat

Results

molecular target: monoamine oxidase B

Location

supporting information

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

liver homogenate of rat

Further Details (Pharmacological Data)

inhibition constant (Ki); Ki related to: monoamine oxidase B

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

1.08 μmol/l

Location

supporting information

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

brain mitochondria of Sprague-Dawley rat

Concentration (Pharmacological Data)

0.1 - 100 μmol/l

Kind of Dosing (Pharmacological Data)

DMSO solution

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Further Details (Pharmacological Data)

IC50 related to: monoamine oxidase-A; inhibitory concentration (IC)

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

6.8 μmol/l

Shi, Lei; Yang, Ying; Li, Zi-Lin; Zhu, Zhen-Wei; Liu, Chang-Hong; Zhu, Hai-Liang; Bioorganic and Medicinal Chemistry; vol. 18; nb. 4; (2010); p. 1659 - 1664, View in Reaxys 83 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

brain mitochondria of Sprague-Dawley rat

Concentration (Pharmacological Data)

0.1 - 100 μmol/l

Kind of Dosing (Pharmacological Data)

DMSO solution

Results

molecular target: monoamine oxidase-A

Shi, Lei; Yang, Ying; Li, Zi-Lin; Zhu, Zhen-Wei; Liu, Chang-Hong; Zhu, Hai-Liang; Bioorganic and Medicinal Chemistry; vol. 18; nb. 4; (2010); p. 1659 - 1664, View in Reaxys 84 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

brain mitochondria of Sprague-Dawley rat

Concentration (Pharmacological Data)

0.1 - 100 μmol/l

Kind of Dosing (Pharmacological Data)

DMSO solution

Further Details (Pharmacological Data)

IC50 related to: monoamine oxidase-B; inhibitory concentration (IC)

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

> 100 μmol/l

Shi, Lei; Yang, Ying; Li, Zi-Lin; Zhu, Zhen-Wei; Liu, Chang-Hong; Zhu, Hai-Liang; Bioorganic and Medicinal Chemistry; vol. 18; nb. 4; (2010); p. 1659 - 1664, View in Reaxys 85 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

liver monoamine oxidase of rat

Further Details (Pharmacological Data)

pargyline used for selective monoamine oxidase B activity suppression; inhibition constant (Ki); Ki related to: monoamine oxidase A

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

5.53 nmol/l

Karuppasamy, Muthukumar; Mahapatra, Manojkumar; Yabanoglu, Samiye; Ucar, Gulberk; Sinha, Barij Nayan; Basu, Arijit; Mishra, Nibha; Sharon, Ashoke; Kulandaivelu, Umasankar; Jayaprakash, Venkatesan; Bioorganic and Medicinal Chemistry; vol. 18; nb. 5; (2010); p. 1875 - 1881, View in Reaxys 86 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

liver monoamine oxidase of rat

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Further Details (Pharmacological Data)

pargyline used for selective monoamine oxidase B activity suppression

Results

molecular target: monoamine oxidase A

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

liver monoamine oxidase of rat

Further Details (Pharmacological Data)

clorgyline used for selective monoamine oxidase A activity suppression

Results

molecular target: monoamine oxidase B

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

liver monoamine oxidase of rat

Further Details (Pharmacological Data)

clorgyline used for selective monoamine oxidase A activity suppression; inhibition constant (Ki); Ki related to: monoamine oxidase B

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

1080 nmol/l

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

recombinant MAO-A of human

Kind of Dosing (Pharmacological Data)

comparative comp. dissolved in sodium phosphate buffer, pH 7.4

Further Details (Pharmacological Data)

fluorometric method; MAO-A: monoamine oxidase A; inhibitory concentration (IC)

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

361.38 μmol/l

Location

supporting information

Alcaro, Stefano; Gaspar, Alexandra; Ortuso, Francesco; Milhazes, Nuno; Orallo, Francisco; Uriarte, Eugenio; Yanez, Matilde; Borges, Fernanda; Bioorganic and Medicinal Chemistry Letters; vol. 20; nb. 9; (2010); p. 2709 2712, View in Reaxys 90 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

recombinant MAO-A of human

Kind of Dosing (Pharmacological Data)

comparative comp. dissolved in sodium phosphate buffer, pH 7.4

Further Details (Pharmacological Data)

fluorometric method; MAO-A: monoamine oxidase A

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Results

molecular target: MAO-A

Location

supporting information

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

microsomal recombinant monoamine oxidase A of human

Kind of Dosing (Pharmacological Data)

comparative compound dissolved in deionized water

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

361382 nmol/l

Chimenti, Franco; Secci, Daniela; Bolasco, Adriana; Chimenti, Paola; Granese, Arianna; Carradori, Simone; MacCioni, Elias; Cardia, M. Cristina; Yanez, Matilde; Orallo, Francisco; Alcaro, Stefano; Ortuso, Francesco; Cirilli, Roberto; Ferretti, Rosella; Distinto, Simona; Kirchmair, Johannes; Langer, Thierry; Bioorganic and Medicinal Chemistry; vol. 18; nb. 14; (2010); p. 5063 - 5070, View in Reaxys 92 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

microsomal recombinant monoamine oxidase A of human

Kind of Dosing (Pharmacological Data)

comparative compound dissolved in deionized water

Results

molecular target: monoamine oxidase A

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

microsomal recombinant monoamine oxidase A of human

Concentration (Pharmacological Data)

500 μmol/l

Kind of Dosing (Pharmacological Data)

comparative compound dissolved in deionized water

Further Details (Pharmacological Data)

centrifugation-ultrafiltration method

Type (Pharmacological Data)

percent inhibition before washing

Value of Type (Pharmacological Data)

86.75 percent

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

microsomal recombinant monoamine oxidase A of human

Concentration (Pharmacological Data)

500 μmol/l

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Kind of Dosing (Pharmacological Data)

comparative compound dissolved in deionized water

Further Details (Pharmacological Data)

centrifugation-ultrafiltration method

Results

molecular target: monoamine oxidase A

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

microsomal recombinant monoamine oxidase A of human

Concentration (Pharmacological Data)

500 μmol/l

Kind of Dosing (Pharmacological Data)

comparative compound dissolved in deionized water

Further Details (Pharmacological Data)

centrifugation-ultrafiltration method

Type (Pharmacological Data)

percent inhibition after repeated washing

Value of Type (Pharmacological Data)

10.26 percent

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

microsomal recombinant monoamine oxidase A of human

Concentration (Pharmacological Data)

<= 100 μmol/l

Kind of Dosing (Pharmacological Data)

comparative compound dissolved in deionized water

Results

molecular target: monoamine oxidase A

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

microsomal recombinant monoamine oxidase A of human

Concentration (Pharmacological Data)

<= 100 μmol/l

Kind of Dosing (Pharmacological Data)

comparative compound dissolved in deionized water

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

361382 nmol/l

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Cirilli, Roberto; Ferretti, Rosella; Distinto, Simona; Kirchmair, Johannes; Langer, Thierry; Bioorganic and Medicinal Chemistry; vol. 18; nb. 14; (2010); p. 5063 - 5070, View in Reaxys 98 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

recombinant monoamine oxidase A of human

Kind of Dosing (Pharmacological Data)

as solution in sodium phosphate buffer (0.05 mol/l, pH 7.4)

Further Details (Pharmacological Data)

inhibitory concentration (IC)

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

361.38 μmol/l

Location

supporting information

Chimenti, Franco; Bolasco, Adriana; Secci, Daniela; Chimenti, Paola; Granese, Arianna; Carradori, Simone; Yanez, Matilde; Orallo, Francisco; Ortuso, Francesco; Alcaro, Stefano; Bioorganic and Medicinal Chemistry; vol. 18; nb. 15; (2010); p. 5715 - 5723, View in Reaxys 99 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

recombinant monoamine oxidase A of human

Kind of Dosing (Pharmacological Data)

as solution in sodium phosphate buffer (0.05 mol/l, pH 7.4)

Further Details (Pharmacological Data)

competitive inhibition constant (Ki)

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

2.03 μmol/l

Location

supporting information

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

recombinant monoamine oxidase A of human

Kind of Dosing (Pharmacological Data)

as solution in sodium phosphate buffer (0.05 mol/l, pH 7.4)

Further Details (Pharmacological Data)

noncompetitive inhibition constant (Ki)

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

6.47 μmol/l

Location

supporting information

enzyme activity; inhibition of

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Species or Test-System (Pharmacological Data)

recombinant monoamine oxidase A of human

Concentration (Pharmacological Data)

500 μmol/l

Kind of Dosing (Pharmacological Data)

as solution in sodium phosphate buffer (0.05 mol/l, pH 7.4)

Type (Pharmacological Data)

inhibition before washing

Value of Type (Pharmacological Data)

86.75 percent

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

recombinant monoamine oxidase A of human

Concentration (Pharmacological Data)

500 μmol/l

Kind of Dosing (Pharmacological Data)

as solution in sodium phosphate buffer (0.05 mol/l, pH 7.4)

Results

molecular target: monoamine oxidase A

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

recombinant monoamine oxidase A of human

Kind of Dosing (Pharmacological Data)

as solution in sodium phosphate buffer (0.05 mol/l, pH 7.4)

Further Details (Pharmacological Data)

at 100 μmol/l inhibition was 40-45percent; competitive inhibition constant (Ki)

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

2.03 μmol/l

Location

supporting information

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

recombinant monoamine oxidase A of human

Kind of Dosing (Pharmacological Data)

as solution in sodium phosphate buffer (0.05 mol/l, pH 7.4)

Further Details (Pharmacological Data)

at 100 μmol/l inhibition was 40-45percent; noncompetitive inhibition constant (Ki)

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

6.47 μmol/l

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Location

supporting information

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

recombinant monoamine oxidase A of human

Kind of Dosing (Pharmacological Data)

as solution in sodium phosphate buffer (0.05 mol/l, pH 7.4)

Further Details (Pharmacological Data)

at 100 μmol/l inhibition was 40-45percent

Results

molecular target: monoamine oxidase A

Location

supporting information

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

recombinant monoamine oxidase A of human

Kind of Dosing (Pharmacological Data)

as solution in sodium phosphate buffer (0.05 mol/l, pH 7.4)

Further Details (Pharmacological Data)

at 100 μmol/l inhibition was 40-45percent; uncompetitive inhibition constant (Ki)

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

4.44 μmol/l

Location

supporting information

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

recombinant monoamine oxidase A of human

Kind of Dosing (Pharmacological Data)

as solution in sodium phosphate buffer (0.05 mol/l, pH 7.4)

Further Details (Pharmacological Data)

at 100 μmol/l inhibition was 40-45percent; inhibitory concentration (IC)

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

361.38 μmol/l

Location

supporting information

enzyme activity; inhibition of recombinant monoamine oxidase A of human

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Concentration (Pharmacological Data)

500 μmol/l

Kind of Dosing (Pharmacological Data)

as solution in sodium phosphate buffer (0.05 mol/l, pH 7.4)

Type (Pharmacological Data)

inhibition after repeated washing

Value of Type (Pharmacological Data)

10.26 percent

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

recombinant monoamine oxidase A of human

Kind of Dosing (Pharmacological Data)

as solution in sodium phosphate buffer (0.05 mol/l, pH 7.4)

Results

molecular target: monoamine oxidase A

Location

supporting information

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

recombinant monoamine oxidase A of human

Kind of Dosing (Pharmacological Data)

as solution in sodium phosphate buffer (0.05 mol/l, pH 7.4)

Further Details (Pharmacological Data)

uncompetitive inhibition constant (Ki)

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

4.44 μmol/l

Location

supporting information

Effect (Pharmacological Data)

antidepressive

Species or Test-System (Pharmacological Data)

Swiss albino mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

30 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in DMSO and administered thrice in 24 h duration at t = 0, 18 and 24 h

Further Details (Pharmacological Data)

tail suspension test; duration of immobility = 175.3 s (control); mass of species: 22 g

Type (Pharmacological Data)

duration of immobility

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Value of Type (Pharmacological Data)

55.8 s

Shelke, Suhas M.; Bhosale, Sharad H.; Bioorganic and Medicinal Chemistry Letters; vol. 20; nb. 15; (2010); p. 4661 - 4664, View in Reaxys 112 of 239

Effect (Pharmacological Data)

antidepressive

Species or Test-System (Pharmacological Data)

Swiss albino mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

30 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in DMSO and administered thrice in 24 h duration at t = 0, 18 and 24 h

Further Details (Pharmacological Data)

tail suspension test; duration of immobility = 175.3 s (control); mass of species: 22 g

Type (Pharmacological Data)

percent decrease in immobility

Value of Type (Pharmacological Data)

68.16 percent

Shelke, Suhas M.; Bhosale, Sharad H.; Bioorganic and Medicinal Chemistry Letters; vol. 20; nb. 15; (2010); p. 4661 - 4664, View in Reaxys 113 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

recombinant monoamine oxidase A of human

Further Details (Pharmacological Data)

production of H2O2 measured; inhibitory concentration (IC)

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

361.38 μmol/l

Chimenti, Franco; Secci, Daniela; Bolasco, Adriana; Chimenti, Paola; Granese, Arianna; Carradori, Simone; Yanez, Matilde; Orallo, Francisco; Sanna, M. Luisa; Gallinella, Bruno; Cirilli, Roberto; Journal of Medicinal Chemistry; vol. 53; nb. 17; (2010); p. 6516 - 6520, View in Reaxys 114 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

recombinant monoamine oxidase A of human

Further Details (Pharmacological Data)

production of H2O2 measured

Results

molecular target: monoamine oxidase A

Effect (Pharmacological Data)

ear swelling; effect on

Species or Test-System (Pharmacological Data)

Balb/c mouse

Route of Application

epicutaneous

Kind of Dosing (Pharmacological Data)

dissolved in 10percent ethanol

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Method (Pharmacological Data)

EXAMPLE 1A study was undertaken in order to evaluate the effect of topical preparations of various test items (TI) and TI combined with Croton oil on ear swelling. Ear thickness was measured before croton oil induced ear swelling and 3 hours post ear edema induction. The various TIs were applied topically 1 hour prior to ear edema sensitization and 2 hours post ear edema sensitization. The difference in ear thickness of the intact ear was subtracted from the ear thickness of the inflamed ear. This value is defined as "ear swelling".Materials and Methods Test System Species/Strain: Mice/Balb/cSource: Harlan Israel, Ltd.Age: Young adults, 6-7 weeks of age at study initiation.Body Weight: Weight variation of animals at the time of treatment initiation did not exceed +/- 15percent of the mean weight.Animals Health: The health status of the animals used in this study was examined on arrival. Only animals in good health were acclimatized to laboratory conditions and were used in the study.Acclimation: 5 days. Housing: During acclimation and following dosing, animals were housed within a limited access rodent facility in conventional cages and kept in groups of maximum10 mice, in polypropylene cages, fitted with solid bottoms and filled with sterile wood shavings as bedding material.Food and Water: Animals were provided with ad libitum - a commercial sterile rodent diet and free access to sterile drinking water, supplied to each cage via polyethylene bottles with stainless steel sipper tubes. Feed lot analysis of the diet batch used in the study was included in the archives with the study data.Environment: Automatically controlled environmental conditions were set to maintain temperature at 20 - 24°C with a relative humidity (RH) of 30 - 70percent, a 12:12 hour light: dark cycle and 10-30 air changes/hr in the study room. Temperature andRH were monitored daily.Identification: Animals were given a unique animal identification ear number.This number also appeared on a cage card, visible on the front of each cage. The cage card also contained the study number, and all other relevant details as to treatment group and dose level.Randomization: Animals were randomly assigned to experimental groups.Termination: At the end of the study surviving animals were euthanized byIsoflurane.Test groups and dosagesThe Experimental groups used in this study are listed in Table 1 below. Table 1 - the 12 experimental groups comprising the studyTest Procedure 100 mL (5OmL each side) of freshly prepared Croton oil in acetone (2.5percentv/v) solution was applied on Left ear on Study Day 0 to induce sensitization. Prior to sensitization animals were anesthetized. Ear thickness was measured 24 hours prior to croton oil sensitization; this measurement served as a baseline. On sensitization day, the animals were anesthetized using Ketamine and Xylazine formulation. Then, the animals were administered with TI topically. One hour later the animals were introduced to croton oil sensitization (50μL). Two hours post croton oil sensitization the animals were administered with TI again. Three hours post croton oil sensitization the ear thickness of the animals were measured again. TIs were administered twice, the first dose was 1 hour prior to croton oil sensitization and the second time was 2 hours post croton oil sensitization. All TIs were dissolved in 10percent Ethanol and were applied topically on the surface of the sensitized ear.Observations and ExaminationsDetermination of individual body weights of animals was made one day before sensitization phase. A single person was responsible for ear thickness measurement throughout the entire study. The ear thickness of both left and right ears was measured using analogue calipers (Instrumentation 0.01mm L-Ol) on 2 occasions: 24 hours prior to croton oil sensitization, and 3 hours post croton oil sensitization.All data are presented in MEAN+/-SEM. T-test, two tailed, unpaired was applied to all data. P value was considered significant

Results

ear thickness inhibition (percent) = 52

Location

Page/Page column 7; 37-43; figure 1/3

Patent; DEKEL PHARMACEUTICALS LTD.; KINDLER, Seth; SHMULEWITZ, Ascher; WO2010/13240; (2010); (A1) English, View in Reaxys 116 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

liver mitochondrial homogenate of rat

Further Details (Pharmacological Data)

MAO-A: monoamine oxidase A isoform; inhibitory concentration (IC); IC50 related to: MAO-A

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

5.7 μmol/l

Goekhan-Kelekci, Nesrin; Simsek, Oe. Oezguen; Ercan, Ayse; Yelekci, Kemal; Sahin, Z. Sibel; Isik, Samil; Ucar, Guelberk; Bilgin, A. Altan; Bioorganic and Medicinal Chemistry; vol. 17; nb. 18; (2009); p. 6761 - 6772, View in Reaxys

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117 of 239

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

liver mitochondrial homogenate of rat

Further Details (Pharmacological Data)

MAO-A: monoamine oxidase A isoform; inhibition constant (Ki); Ki related to: MAO-A

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

5.53 nmol/l

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

liver mitochondrial homogenate of rat

Further Details (Pharmacological Data)

MAO-B: monoamine oxidase B isoform; inhibitory concentration (IC); IC50 related to: MAO-B

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

89.55 μmol/l

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

liver mitochondrial homogenate of rat

Further Details (Pharmacological Data)

MAO-B: monoamine oxidase B isoform; inhibition constant (Ki); Ki related to: MAO-B

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

1.08 μmol/l

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

liver mitochondrial homogenate of rat

Further Details (Pharmacological Data)

MAO-A: monoamine oxidase A isoform

Results

molecular target: MAO-A

enzyme activity; inhibition of liver mitochondrial homogenate of rat

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Further Details (Pharmacological Data)

MAO-B: monoamine oxidase B isoform

Results

molecular target: MAO-B

exploratory activity; effect on

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)

single dose suspended in 1percent aqueous solution of Tween 80, injected in volume of 2 ml/kg

Method (Pharmacological Data)

title comp. administered to rats alone or with SB-399885 (3 mg/kg i.p., 30 min after title comp.); 60 min later exploratory activity (EA) assessed by open field test

Further Details (Pharmacological Data)

vehicle control; SB-399885: selective 5-HT6 receptor antagonist

Comment (Pharmacological Data)

No effect

Wesolowska, Anna; Nikiforuk, Agnieszka; European Journal of Pharmacology; vol. 582; nb. 1-3; (2008); p. 88 93, View in Reaxys 123 of 239 Effect (Pharmacological Data)

antidepressant

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

20 - 30 mg/kg

Kind of Dosing (Pharmacological Data)

single dose suspended in 1percent aqueous solution of Tween 80 in volume of 2 ml/kg

Method (Pharmacological Data)

title comp. administered to rats alone or at 20 mg/kg with SB-399885 (3 mg/kg i.p., 30 min after title comp.); 60 min later anti-immobility effect assessed with forced swim test (animal model sensitive to antidepressant treatment)

Further Details (Pharmacological Data)

vehicle control; SB-399885: selective 5-HT6 receptor antagonist; IT: immobility time

Results

title comp. alone (at 30 mg/kg) and with SB-399886 decreased IT; fig.

Wesolowska, Anna; Nikiforuk, Agnieszka; European Journal of Pharmacology; vol. 582; nb. 1-3; (2008); p. 88 93, View in Reaxys 124 of 239 Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

bovine brain mitochondria

Kind of Dosing (Pharmacological Data)

solution in DMSO

Further Details (Pharmacological Data)

inhibition constant (Ki); Ki related to: monoamine oxidase A

Type (Pharmacological Data)

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Value of Type (Pharmacological Data)

11.5 μmol/l

La Regina, Giuseppe; Silvestri, Romano; Gatti, Valerio; Lavecchia, Antonio; Novellino, Ettore; Befani, Olivia; Turini, Paola; Agostinelli, Enzo; Bioorganic and Medicinal Chemistry; vol. 16; nb. 22; (2008); p. 9729 - 9740, View in Reaxys 125 of 239 Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

bovine brain mitochondria

Kind of Dosing (Pharmacological Data)

solution in DMSO

Results

molecular target: monoamine oxidase A

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

bovine brain mitochondria

Kind of Dosing (Pharmacological Data)

solution in DMSO

Results

molecular target: monoamine oxidase B

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

bovine brain mitochondria

Kind of Dosing (Pharmacological Data)

solution in DMSO

Further Details (Pharmacological Data)

inhibition constant (Ki); Ki related to: monoamine oxidase B

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

> 100 μmol/l

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

liver homogenate MAO-A of rat

Further Details (Pharmacological Data)

IC50 values determine at 0 - 60 min preincub.

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

3.9 - 5.58 μmol/l

Location

supporting information

Jayaprakash, Venkatesan; Sinha, Barij N.; Ucar, Gulberk; Ercan, Ayse; Bioorganic and Medicinal Chemistry Letters; vol. 18; nb. 24; (2008); p. 6362 - 6368, View in Reaxys

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129 of 239 Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

liver homogenate MAO of rat

Further Details (Pharmacological Data)

title comp. dissolved in DMSO

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

2.25 μmol/l

Location

supporting information

Jayaprakash, Venkatesan; Sinha, Barij N.; Ucar, Gulberk; Ercan, Ayse; Bioorganic and Medicinal Chemistry Letters; vol. 18; nb. 24; (2008); p. 6362 - 6368, View in Reaxys 130 of 239 Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

monoamine oxidase A of human

Results

molecular target: monoamine oxidase A

behavioural symptoms

Species or Test-System (Pharmacological Data)

Albino Swiss mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. suspended in 1percent aqueous solution of Tween 80 immediately before administration

Method (Pharmacological Data)

mice administered with title comp. alone or with SB 269970, 60 min before test; placed individually in photoresistor actometers; number of crossings of light beams counted for 6min; spontaneous locomotor activity of mice recorded

Results

title comp. slightly but significantly reduced the spontaneous locomotor activity

Wesolowska, Anna; Tatarczynska, Ewa; Nikiforuk, Agnieszka; Chojnacka-Wojcik, Ewa; European Journal of Pharmacology; vol. 555; nb. 1; (2007); p. 43 - 47, View in Reaxys 132 of 239 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Albino Swiss mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. dissolved in distilled water

Method (Pharmacological Data)

mice was administered with SB 269970 first + title comp., 30 and 60 min before test; individually placed in glass cylinder (25 cm high, 10 cm in diameter) containing 6 cm of water (23-25 deg C), and left therein for 6 min; immobility was measured

Further Details (Pharmacological Data)

mice regarded as immobile when they remained floating in water, making only small movements to keep head above

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Results

title comp. co-administered with subactive doses of antidepressants revealed a pronounced, statistically significant anti-immobility effect; fig.

Wesolowska, Anna; Tatarczynska, Ewa; Nikiforuk, Agnieszka; Chojnacka-Wojcik, Ewa; European Journal of Pharmacology; vol. 555; nb. 1; (2007); p. 43 - 47, View in Reaxys 133 of 239 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Albino Swiss mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

10 - 20 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. suspended in a 1percent aqueous solution of Tween 80 immediately before administration

Method (Pharmacological Data)

mice administered with title comp. 60 min before test; individually placed in glass cylinder (25 cm high, 10 cm in diameter) containing 6 cm of water maintained at 23-25 deg C, and were left therein for 6 min; immobility measured

Further Details (Pharmacological Data)

mice regarded as immobile when they remained floating in water, making only small movements to keep head above

Results

title comp. at 10 mg/kg did not affect the immobility time of mice in the forced swimming test; at 20 mg/kg title comp. induced a significant anti-immobility effect; fig.

Wesolowska, Anna; Tatarczynska, Ewa; Nikiforuk, Agnieszka; Chojnacka-Wojcik, Ewa; European Journal of Pharmacology; vol. 555; nb. 1; (2007); p. 43 - 47, View in Reaxys 134 of 239 Effect (Pharmacological Data)

cytotoxicity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat neural stem cells

Concentration (Pharmacological Data)

10 - 400 μmol/l

Kind of Dosing (Pharmacological Data)

vehicle: 0.1 percent DMSO

Method (Pharmacological Data)

cells were exposed to title comp. for 24 - 72 h; cell viability were analyzed using MTT assay

Further Details (Pharmacological Data)

vehicle control; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

Results

title comp. at 50 μmol/l increased cell survival, but decreased cell viability at concentration > 75 μmol/l; maximum of both effects at 72 h (figure)

mRNA expression; induction of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat neural stem cells

Concentration (Pharmacological Data)

50 μmol/l

Kind of Dosing (Pharmacological Data)

vehicle: 0.1 percent DMSO

Method (Pharmacological Data)

cells were exposed to title comp. for 3 - 5 days; DMEM and F-12 nutrient (1/1); total RNA was extracted; mRNA expression of Bcl-2; Bcl-xL, Bax, Fas, MAP2 and nestin were detected; real-time RT-PCR

Further Details (Pharmacological Data)

vehicle control; DMEM: Dulbecco's modified Eagle's medium; RT-PCR: reverse transcription-polymerase chain reaction

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Results

title comp. significantly upregulated mRNA levels of Bcl-2 and Bcl-xL and slightly increased mRNA levels of MAP2 and nestin, but did not change expression of Bax and Fas (figure)

protein expression; induction of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat neural stem cells

Concentration (Pharmacological Data)

50 μmol/l

Kind of Dosing (Pharmacological Data)

vehicle: 0.1 percent DMSO

Method (Pharmacological Data)

cells were exposed to title comp. for 5 days; DMEM and F-12 nutrient (1/1); protein expression of Bcl-2 was determined; immunofluorescent staining

Further Details (Pharmacological Data)

vehicle control; DMEM: Dulbecco's modified Eagle's medium

Results

title comp. increased protein expression of Bcl-2 (figure)

apoptosis; inhibition of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat neural stem cells

Concentration (Pharmacological Data)

50 μmol/l

Kind of Dosing (Pharmacological Data)

vehicle: 0.1 percent DMSO

Method (Pharmacological Data)

cells were exposed to title comp. for 48 h; FasL (200 ng/ml)-induced apoptosis; annexin-5 activity was measured using flow cytometry; caspase 8 and caspase 3 activities were detected by ELISA assay

Further Details (Pharmacological Data)

vehicle control

Results

title comp. significantly decreased apoptotic activities of annexin-5 and caspases 8 and 3 (figure)

apoptosis; inhibition of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat neural stem cells

Concentration (Pharmacological Data)

50 μmol/l

Kind of Dosing (Pharmacological Data)

vehicle: 0.1 percent DMSO

Method (Pharmacological Data)

cells were exposed to title comp. for 48 h; FasL (200 ng/ml)-induced apoptosis was determined; TUNEL assay

Further Details (Pharmacological Data)

vehicle control; TUNEL: terminal dUTP nick-end labeling

Results

title comp. prevented FasL-induced apoptosis (figure)

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cell differentiation; induction of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat neural stem cells

Concentration (Pharmacological Data)

50 μmol/l

Kind of Dosing (Pharmacological Data)

vehicle: 0.1 percent DMSO

Method (Pharmacological Data)

neuropheres-like cells were seeded on polyornithine-coating plates with 2 percent FBS; treatment with title comp. for 7 days; morphological development of neurons was observed

Further Details (Pharmacological Data)

vehicle control; further investigations using pan-caspase inhibitor (Z-VAD-FMK), selective inhibitor of caspase-3 (Z-DEVD-FMK), or MEK inhibitor (PD98059)

Results

title comp. increased number of neurite, neurite length and primary dendrities in 3 - 7 days; PD98059 inhibited effect of title comp.; Z-VAD-FMK and Z-DEVD-FMK had no effect (figure)

protein expression; induction of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat neural stem cells

Concentration (Pharmacological Data)

50 μmol/l

Kind of Dosing (Pharmacological Data)

vehicle: 0.1 percent DMSO

Method (Pharmacological Data)

neuropheres-like cells were seeded on polyornithine-coating plates with 2 percent FBS; treatment with title comp. for 1 - 5 days; protein expression of Bcl-2, phosphorylated ERK 1/2, total ERK 1/2 were determined in lysate; Western blotting

Further Details (Pharmacological Data)

vehicle control; ERK: extracellular-regulated kinase; further investigations using MEK inhibitor (PD98059)

Results

title comp. time-dependently elevated Bcl-2 protein expression and increased expression of phosphorylated ERK 1/2 after 3 - 5 days, but did not change total amount of ERK; PD98059 inhibited effect of title comp. (figure)

transmitter releasing

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat neural stem cells

Concentration (Pharmacological Data)

50 μmol/l

Kind of Dosing (Pharmacological Data)

vehicle: 0.1 percent DMSO

Method (Pharmacological Data)

cells treated with title comp. for 1 - 7 days; DMEM and F-12 nutrient (1/1); level of 5-HT in medium was measured; HPLC-ECD

Further Details (Pharmacological Data)

vehicle control; DMEM: Dulbecco's modified Eagle's medium; HPLC-ECD: high-performance liquid chromatography coupled to electrochemical detection; further investigations using MEK inhibitor (PD98059)

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Results

title comp. significantly increased 5-HT levels in 3 - 7 days; PD98059 inhibited effect of title comp. (figure)

cerebral oedema; effect on

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Method (Pharmacological Data)

EXAMPLE The inventors have demonstrated a protection of the moclobemide on cerebral oedema induced by triethyltin (TET) chloride. Moreover, the effect of moclobemide has also been studied on the disruptions induced by TET for the 3 following parameters: weight development, neurological index and ambulatory activity. 1. Material and Methods 1.1. Model Cerebral oedema induced triethyltin (TET) chloride in the rat is a physiopathological model for the study of substances recommended in the treatment of certain cerebrovascular ailments (Linee et al., 1984 Ann. Pharm. Fr. 42, 431-442). Intoxication with TET is also a useful toxicological tool for testing products which act at the cerebral level in the elderly person for testing new products in senescence (Bentue-Ferer et al., 1985 Exp. Aging Res. 11, 137-141) Cerebral oedema due to TET is a chronic oedema, appearing progressively and spontaneously reversible on condition that the intoxication is stopped. This oedema develops exclusively at the level of the brain and of the spinal cord. Cerebral oedema is characterised by an increase in the contents of water, sodium and chlorides without significant modification of the potassium content. The oedema is reflected in a specific attack on the white matter (Naruse et al., 1982 J. Neurosurg. 56, 747-752), with a widening of the intramyelinic spaces and attack on the myelin (Kirschner and Sapirstein, 1982 J. Neurocytol. 11, 559-569). The myelin of the central nervous system has the potential to recover its integrity after oedematous damage by the withdrawal of the accumulated fluid (Yanagisawa et al., 1990 Neurochem. Res. 15, 483-486). The scale of the oedema, which is accompanied by a weight loss and peripheral neurological disorders, is proportional to the dose of TET. It has been demonstrated in particular that: The administration of TET (bromide) at 1 mg/kg/day intraperitoneally for 7 days in the rat increases the percentage of water in the white matter (from 78 to 82percent), but not in the grey matter (Naruse et al., 1982 J. Neurosurg. 56, 747-752); The administration of TET (hydrochloride) in drinking water at 2-3percent, for 15 days in the rat, increases the percentage of water from 78.0 to 80.0percent (Borzeix and Cahn, 1984 Int. J. Clin. Pharmacol. Res. 4, 259-261); The administration of TET (chloride) at 2 mg/kg/day orally for 5 days in the rat increases the percentage of water from 76-77 to 79-80percent (Linee et al., 1984 Ann. Pharm. Fr. 42, 431-442) The administration of TET (chloride) at 0.002percent in drinking water for 14 days in the rat increases the percentage of water from 78.3 to 81.1percent (Otani et al., 1986 Acta Neuropathol. (Berl) 69, 54-65). According to a preventive protocol, the substances to be tested are administered during the intoxication with tin and their activities are measured after 5 days. Under these conditions, it has been shown that certain cerebrovascular medicaments are active, such as dihydroergotoxin, (-)eburnamonine and vincamine (Linee et al., 1984 Ann. Pharm. Fr. 42, 431-442).

Location

Page/Page column 3-5; sheet 1-2

Comment (Pharmacological Data)

No effect

Patent; Le Guern, Marie-Emmanuelle; Girard, Philippe; Gillardin, Jean-Marie; Berthon-Cedille, Laurence; Hublot, Bernard; US2006/276472; (2006); (A1) English, View in Reaxys 143 of 239 Effect (Pharmacological Data)

body weight; effect on

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Method (Pharmacological Data)

Body Weight At the level of the development of the body weight of the rats, TET leads to a significant drop in weight at day 4 (Table 2 and FIGS. 2A, 2B). Moclobemide administered alone disrupts the weight gain. At the 2 doses utilised, the body weight of the rats is significantly lower at day 4 relative to the control groups. However, in the presence of TET and of moclobemide at 2.x.50 mg/kg/day, it is noted that the body weight of the rats at day 4 has not decreased as much as that of the group receiving only TET. In this case, the moclobemide partially prevents the drop in weight induced by the TET. In the presence of

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TET and of moclobemide at 2.x.100 mg/kg/day, it may be noted that the drop in weight observed between day 3 and day 4 in the group receiving only TET is not produced. Therefore moclobemide prevents the drop in weight induced by the TET. Results

title compound administered alone disrupts weight gain; at 2 doses utilised, the body weight of the rats is significantly lower at day 4 relative to the control groups; figures given

Location

Page/Page column 3; 5; sheet 3-4

neurological index; effect on

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Method (Pharmacological Data)

Neurological Index The administration of moclobemide at 2.x.50 or 2.x.100 mg/kg/day for 5 days does not lead to any behavioural sign in the rat (Table 3 and FIG. 3A, 3B). TET at 3 mg/kg/day, for 5 days, leads to a significant increase in the neurological index from day 3, with a much stronger effect at day 4, indicating substantial neurological troubles. The concomitant administration of moclobemide at 2.x.50 mg/kg/day and of TET greatly reduces this neurological index at day 3, and reduces it by half at day 4. At the dose of 2.x. 100 mg/kg/day, moclobemide also inhibits the effect of TET.

Location

Page/Page column 3; 6; sheets 5-6

Comment (Pharmacological Data)

No effect

ambulatory activity; effect on

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Method (Pharmacological Data)

Ambulatory Activity The administration of moclobemide at 2.x.50 mg/kg/day for 5 days does not lead to any significant effect on the ambulatory activities in the rat (Table 4 and FIGS. 4A, 4B, 4C). On the other hand, at the dose of 2.x.100 mg/kg/day, the administration of moclobemide significantly decreases the ambulatory activities at day 4 (Table 5 and FIGS. 5A, 5B, 5C). TET at 3 mg/kg/day, for 5 days, leads to a great decrease in the ambulatory activities at day 4, with and almost total inhibition of the vertical ambulatory activity. The concomitant administration of moclobemide at 2.x.50 or 2.x.100 mg/kg/day and of TET does not suppress the effect of TET, but reduces it partially at the level of the vertical ambulatory activity.

Results

administration of title compound at 2*50 mg/kg/day for 5 days does not lead to any significant effect on the ambulatory activities in the rat; at the dose of 2*100 mg/kg/day, the administration of moclobemide significantly decreases the ambulatory activities at day 4; figures given

Location

Page/Page column 3; 6-7; sheets 7-12

apathy; treatment of

Species or Test-System (Pharmacological Data)

human

Sex

female

Route of Application

peroral

Method (Pharmacological Data)

A 44 year female Caucasian presented in referral for apathy. This individual gave 5 year history of behavioral change followed by occupational impairment, social withdrawal then frankly decreased complex attention. A diagnosis of frontotemporal dementia was made. A treatment plan for apathy was made whereby low dose moclobemide was titrated

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against low dose risperidone, commenced approximately 6 months following the initial diagnosis. Subsequently (approximately 2 months later), improvement was independently documented. A further independent evaluation was made approximately 1 year and 1 month after treatment began and improvement in her apathy was noted. Approximately 5 months later risperidone was discontinued for pharmacokinetic limitations and olanzapine commenced. With changes in the dose of olanzapine, the apathy was again effectively treated. The patient continued her work developing an advocacy network for persons with dementia and traveling internationally. This precipitated an independent medical evaluation by her disability insurer, which substantiated her diagnosis and the treatment effect. The combination therapy (moclobemide and risperidone or olanzapine) exhibited a clinical efficacy that appeared to be greater than the cumulative effect that would have been expected if the patient had been treated with an equivalent amount of moclobemide alone or with an equivalent amount of risperidone or olanzapine alone Results

combination therapy (title comp. and risperidone or olanzapine) exhibited a clinical efficacy that appeared to be greater than the cumulative effect that would have been expected if the patient had been treated with an equivalent amount of title comp. alone or with an equivalent amount of risperidone or olanzapine alone

Location

Page/Page column 30

Patent; SHELDON, Leslie James; WO2005/53703; (2005); (A1) English, View in Reaxys 147 of 239 Effect (Pharmacological Data)

Parkinson desease; treatment of

Species or Test-System (Pharmacological Data)

human

Sex

male

Route of Application

peroral

Method (Pharmacological Data)

A 79 year old retired sailor developed Parkinson's disease more than 5 years before admission to hospital. After the onset of Parkinson's disease he developed decreased motivation and decreased interest. The severity of the apathy progressed to a near total lack of initiative. A trial of methylphenidate for apathy was unsuccessful. He was admitted to hospital with anxiety, severe apathy and constipation. He was unable to function at home leading to caregiver burn out. Core symptoms of delirium were absent. A shuffling gait devoid of heel strike or toe push was observed. Arm swing was decreased. This gentleman described decreased motivation in face of clear enjoyment of family visits and the sunshine outside. His capacity for projective pleasure was preserved. He was satisfied with his accomplishments over his life. He felt his quality of life was reduced by his lack initiative. Objective mood and affect were flat. Thought form was marked by latency but progressed logically to a goal oriented conclusion. Thought content was free of delusions or hallucinations. Language was mildly impaired with paraphasic errors noted. Remote memories were difficult to recall and approximately correct. His sense of humor and capacity for abstraction were preserved. Wechsler Adult Intelligence Scale -Third Edition (WAIS III) testing revealed mild impairment of attention, praxis, reasoning, memory, response latency and difficulty in self correcting. This was judged consistent with Parkinson's disease by the registered psychologist. An occupational therapy assessment in hospital on day 2 revealed decreased grip strength compromising his ability to dress and decreased range of movement compromising bathing. He could walk four lengths of the hallway. Moclobemide was commenced day 4 at 75 mg. daily, increased to 150 mg. daily on day 8 and decreased to 75 mg daily on day 11. Olanzapine was commenced day 8 at 1.25 mg daily and continued at that dose. Day 8 to 11 demonstrated the absence of depression by every day life. He enjoyed watching the Superbowl. He came into a small financial windfall and developed several plans to spend the money. Increased energy and increased social interaction were observed. Increased spontaneous activity led to independence in Activities of Daily Living (ADL). His walking improved to 400 feet. Day 15 to 17 revealed increased mobile facial expression. He was able to learn, retain and employ movement strategies to eliminate postural hypotension. He was fully independent with his morning routine prior to discharge. He was discharged home independent in ADL.

Results

title comp. was commenced day 4 at 75 mg daily, increased to 150 mg daily on day 8 and decreased to 75 mg daily on day 11; olanzapine was commenced day 8 at 1.25 mg daily and continued at that dose; day 8 to 11 demonstrated the absence of depression by every day life, increased energy and increased social interaction were observed, increased spontaneous activity led to independence in Activities of Daily Living; day 15 to 17 revealed increased mobile facial expression

Location

Page/Page column 31-32

Patent; SHELDON, Leslie James; WO2005/53703; (2005); (A1) English, View in Reaxys

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148 of 239 Effect (Pharmacological Data)

mental status; improvement of

Species or Test-System (Pharmacological Data)

human

Sex

female

Route of Application

peroral

Method (Pharmacological Data)

A 75 year retired nurse lived independently in the community until 2 months prior to admission. A progressive and gradual reduction in social patterns was reported over the preceding two years. However, she traveled internationally during that time. Over the two months prior to admission she became more forgetful, refused support services, further withdrew from the community and described herself as"depressed". She acquired a thrush infection, became dehydrated and lost a great deal of weight. Family and personal psychiatric history was negative. Salient medical history included a remote mastectomy for breast cancer, three vessel coronary bypass, acid peptic disease and hypertension. Admitting mental status examination revealed a cachexic female suffering anxiety and lacking pleasure in previously pleasurable activities. Initiative was absent. Objective mood was dysphoric and affect restricted. Decreased concentration was apparent. The MMSE was 28/28 in nonstandard administration. She was completely dependent for activities of daily living (ADL). Moclobemide was commenced at 200 mg. daily on day 4, increased to 300 mg. daily and day 6 and continued at 300 mg. daily. Risperidone was commenced at 0.5 mg daily on day 7, discontinued on day 14 then restarted at 0.5 mg daily alternating with 0.25 mg. daily and continued as such. The first three days of the admission showed prominent depressed mood in the morning with very limited improvement in the late afternoon. The late afternoon quality of mood and mobility of affect improved by Day 6. By Day 13 pleasure was experienced and her affect mobilized. She described herself as unable to cook, clean for care for herself prior to admission. With step by step instructions she could progress through her Activities of Daily Living (ADL). Shortly after, mild extrapyramidal symptoms emerged. Therefore, risperidone was decreased. Self-toileting emerged on Day 16. By Day 20 she reported an euthymic mood and denied treatment emergent side effects. Examination showed some mobility of affect and normal muscle tone. However, she remained without initiative to commence and complete almost all ADL. By Day 24 self initiation of ADL was consistently observed. From Day 28 forward both self initiation and self supervision of ADL to completion was consistently observed. She resumed her usual hobby of reading on Day 45. Her 3MS score on Day 45 was 80/100. She was discharged to an intermediate care facility where she continued regular activity. Eventually she took up square dancing and returned to international travel.

Results

title comp. was commenced at 200 mg daily on day 4, increased to 300 mg daily and day 6 and continued at 300 mg daily; risperidone was commenced at 0.5 mg daily on day 7, discontinued on day 14 then restarted at 0.5 mg daily alternating with 0.25 mg daily and continued as such; from day 28 forward both self initiation and self supervision of Activities of Daily Living to completion was consistently observed

Location

Page/Page column 31-32

Patent; SHELDON, Leslie James; WO2005/53703; (2005); (A1) English, View in Reaxys 149 of 239 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

20 - 30 mg/kg

Kind of Dosing (Pharmacological Data)

suspended in 1 percent aqueous solution of Tween 80 immediately before administration in a volume of 2 ml/kg

Method (Pharmacological Data)

rats treated with title comp. 1 h before test; allowed to explore open illuminated arena (50 cm from the floor) freely for 3 min; walking time, ambulation (crossing of sector lines), rearing and peeping episodes recorded

Further Details (Pharmacological Data)

further invest. with co-administration (75 min before test) of GR 127935 (10 or 20 mg/kg i.p.), SB 216641 (2 mg/kg i.p.): 5-HT1B/1D, 5-HT1B receptor antagonist, resp.; peeping: looking under arena edge

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Comment (Pharmacological Data)

No effect

Tatarczynska, Ewa; Klodzinska, Aleksandra; Stachowicz, Katarzyna; Chojnacka-Wojcik, Ewa; European Journal of Pharmacology; vol. 487; nb. 1-3; (2004); p. 133 - 142, View in Reaxys 150 of 239 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

20 - 30 mg/kg

Kind of Dosing (Pharmacological Data)

suspended in 1 percent aqueous solution of Tween 80 immediately before administration; used in a volume of 2 ml/kg

Method (Pharmacological Data)

rats allowed 15 min habituation to forced swimming test procedure in water-filled cylinder; treatment with title comp. 1 h before test; forced swimming test performed; duration of immobility measured for 5 min

Further Details (Pharmacological Data)

further invest. with co-administration (75 min. before test) of GR 127935 (10 or 20 mg/kg i.p.), SB 216641 (2 mg/kg i.p.), WAY 100635 (0.1 or 1 mg/kg s.c.): 5-HT1B/1D, 5-HT1B, 5HT1A receptor antagonists, resp.

Results

20 mg/kg title comp. alone or with WAY 100635 did not produce any significant effect on immobility time; 20 mg/kg title comp. in combination with GR 127935 or SB 216641, as well as 30 mg/kg title comp. (alone), had significant anti-immobility effect

enzyme; induction 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 increased by 17 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 152 of 239 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

2.5 - 10 mg/kg

Kind of Dosing (Pharmacological Data)

used as HCl salt; dissolved in deionised water

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Method (Pharmacological Data)

rats were injected with 12.5 μg 6-OHDA into right median forebrain bundle to induce unilateral lesion of nigrostriatal tract; 6 wk later title comp. was administered; circling behaviour was monitored for 60 min as anti-Parkinsonian index

Further Details (Pharmacological Data)

vehicle control; automated rotometers; 6-OHDA: 6-hydroxydopamine; further studies using L-3,4-dihydroxyphenylamine (L-DOPA)

Results

title comp. was ineffective, but significantly potentiated L-DOPA-increased duration of rotational behaviour (figure)

MacInnes, Nicholas; Duty, Susan; British Journal of Pharmacology; vol. 143; nb. 8; (2004); p. 952 - 959, View in Reaxys 153 of 239 Effect (Pharmacological Data)

antioxidant

Species or Test-System (Pharmacological Data)

Wistar rat cortical cells

Concentration (Pharmacological Data)

50 μmol/l

Method (Pharmacological Data)

cells exposed to title comp. for 3 h in Locke's solution, then sodium nitroprusside added and incubation prolonged for 16 h, thereafter lipid peroxidation measured by fluorescence of thiobarbituric acid reactive substances

Comment (Pharmacological Data)

No effect

Boland, Andre; Gerardy, Jean; Mossay, Danielle; Seutin, Vincent; European Journal of Pharmacology; vol. 466; nb. 1-2; (2003); p. 21 - 30, View in Reaxys 154 of 239 Effect (Pharmacological Data)

antioxidant

Species or Test-System (Pharmacological Data)

Wistar rat hippocampal cells

Concentration (Pharmacological Data)

50 μmol/l

Method (Pharmacological Data)

cells exposed to title comp. for 3 h in Locke's solution, then sodium nitroprusside added and incubation prolonged for 8 h, thereafter intracellular peroxides measured by fluorescence with 2,7-dichloro-fluorescein diacetate

Comment (Pharmacological Data)

No effect

Boland, Andre; Gerardy, Jean; Mossay, Danielle; Seutin, Vincent; European Journal of Pharmacology; vol. 466; nb. 1-2; (2003); p. 21 - 30, View in Reaxys 155 of 239 Effect (Pharmacological Data)

neuroprotective

Species or Test-System (Pharmacological Data)

Wistar rat hippocampal cells

Concentration (Pharmacological Data)

1 - 100 μmol/l

Method (Pharmacological Data)

cells exposed to title comp. for 3 h in Locke's solution, then sodium nitroprusside added and incubation prolonged for 16 h; cell death assessed by usual lactate dehydrogenase (LDH) activity assay that measures quantity of LDH released by dying cells

Comment (Pharmacological Data)

No effect

Boland, Andre; Gerardy, Jean; Mossay, Danielle; Seutin, Vincent; European Journal of Pharmacology; vol. 466; nb. 1-2; (2003); p. 21 - 30, View in Reaxys 156 of 239 Effect (Pharmacological Data)

enzyme; inhib. of

Species or Test-System (Pharmacological Data)

adult Wistar rat synaptosomes

Sex

male and female

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Concentration (Pharmacological Data)

50 - 10000 μmol/l

Exposure Period (Pharmacological Data)

50 min

Method (Pharmacological Data)

rats decapitated; brain removed; homogenate prepared, centrifuged; supernatant further centrifuged; pellets resuspended in sucrose sol. and homogenized by polytron; synaptosomes used for monoamino oxidase assay (MAO)

Further Details (Pharmacological Data)

synaptosomes preincubated with title compd. at 37 deg C 30 min before addition of 5-hydroxytryptamine substrate; MAO-A activity detd. by fluorometric method; H2O2 as standard; protein conc. detd. with bovine serum albumine standard

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

275 μmol/l

Results

title compd. inhibited MAO-A activity

receptor; binding activity

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)

dissolved in distilled water; injected once daily for 4 days

Method (Pharmacological Data)

rats killed 24 h after last title comp. injection; brain sections prepared; pretreated with GTP in Tris-HCl; incubated with 4.7 nmol/l <3H>DPDPE for 90 min; <3H>DPDPE autoradiographic binding to δ-opioid receptors in different brain regions determined

Further Details (Pharmacological Data)

<3H>DPDPE: <3H><D-Pen2,D-Pen5>enkephalin; nonspecific binding determined in presence of 4.7 μmol/l unlabeled DPDPE; binding site density (BSD) determined in cortex, amygdala, basal ganglia and miscellaneous

Results

treatment with title comp. induced increase in <3H>DPDPE BSD in layer VIa of frontal cortex (+15 percent), medial posterodorsal amygdaloid nucleus (+8 percent) and cortical posterodorsal amygdaloid nucleus (+27 percent); did not change BSD in other brain regions (table)

Vilpoux, Catherine; Carpentier, Celine; Leroux-Nicollet, Isabelle; Naudon, Laurent; Costentin, Jean; European Journal of Pharmacology; vol. 443; nb. 1-3; (2002); p. 85 - 93, View in Reaxys 158 of 239 Effect (Pharmacological Data)

receptor; binding activity

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)

dissolved in distilled water; injected once daily for 21 days

Method (Pharmacological Data)

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Further Details (Pharmacological Data)

Results

treatment with title comp. induced decrease in <3H>DPDPE BSD in medial posteroventral amygdaloid nucleus (-26 percent) and in external cortex of inferior colliculi (-24 percent); title comp. did not change BSD in other brain regions (table)

receptor; binding activity

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)

dissolved in distilled water; injected once daily for 4 days

Method (Pharmacological Data)

rats killed 24 h after last title comp. injection; brain sections prepared; incubated with 2.5 nmol/l <3H>naloxone for 1 h in Tris buffer; DAMGO-sensitive <3H>naloxone autoradiographic binding to μ-opioid receptors in different brain regions determined

Further Details (Pharmacological Data)

DAMGO: <D-Ala2,MePhe4, Gly-ol5>enkephalin; nonspecific binding determined in presence of 1 μmol/l unlabeled DAMGO; binding site density (BSD) determined in cortex, amygdala, thalamus and miscellaneous

Results

treatment with title comp. induced increase in μ-opioid receptor BSD in frontal cortex (+35 percent) and did not change BSD in other brain regions (table)

receptor; binding activity

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)

dissolved in distilled water; injected once daily for 21 days

Method (Pharmacological Data)

Further Details (Pharmacological Data)

Results

treatment with title comp. induced decrease in μ-opioid receptor BSD in frontal cortex (-23 percent), anterior olfactory nucleus (-37 percent), medial postventral amygdaloid nucleus (-19 percent), ventromedial hypothalamus (-31 percent); had no effect on other regions (table)

biotransformation human liver microsomes

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Concentration (Pharmacological Data)

1.3 mmol/l

Kind of Dosing (Pharmacological Data)

the title comp. was dissolved in methanol

Method (Pharmacological Data)

0.1 mg/ml microsomal protein; 0.1 M phosphate buffer; pH 7.4; with and without NADPHgenerating system: 10 mM glucose 6-phosphate, 10 mM MgCl2, 1 mM NADP+, 0.4 U glucose 6-phosphate dehydrogenase; incubation for 60 min; RP-HPLC; UV-VIS (240 nm)

Further Details (Pharmacological Data)

preincubated before addition of microsomal protein for 5 min at 37 deg C in constant-temperature SW-20 deg C agitate water bath; with and without heating (50 deg C for 1 min) in presence and absence of NADPH-regenerating system; performed in duplicate

Results

< 10 percent of the title comp. was metabolized; velocity of the reaction without heating and with NADPH/without heating and NADPH/with heating and without NADPH/with heating and with NADPH (nmol/mg/min): 1.26/0.00/0.03/1.12

Metabolite XRN (Pharmacological Data)

8920249

Metabolite (Pharmacological Data)

Ro 12-5637

Hoskins; Shenfield; Murray; Gross; Xenobiotica; vol. 31; nb. 7; (2001); p. 387 - 397, View in Reaxys 162 of 239 Effect (Pharmacological Data)

agonist

Species or Test-System (Pharmacological Data)

Sprague-Dawley rats

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

5 - 50 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. admin. dissolved in 20 percent dimethylacetamide/2.5 percent d-glucose and given as 5 mg/ml solution in volume 1 and 3 ml/kg

Method (Pharmacological Data)

in vivo; rats (230-350 g) anesthetized with a combination of α-chloralose, urethane and pentobarbital; 5-8 rats were treated with 5, 15 or 50 mg/kg title comp. or vehicle 122; 10, 30 and 60 min after treatment rats received tyramine (16 μg, i.v.)

Further Details (Pharmacological Data)

interaction of acute title comp. with tyramine; control: effects of tyramine alone tested before testing of title comp.; mean arterial pressure (MAP), heart rate measured before and within 30 s after tyramine injections

Results

dose-dependent potentiation of tyramine pressor response was seen after all doses of title comp., characterized by 92-183 percent peka MAP changes, 6-13-fold increase in MAP AUC and 56-82 percent increases in heart rate (diagrams)

Humphrey, Stephen J.; Curry, James T.; Turman, Chauncey N.; Stryd, Ronald P.; Journal of Cardiovascular Pharmacology; vol. 37; nb. 5; (2001); p. 548 - 563, View in Reaxys 163 of 239 Effect (Pharmacological Data)

agonist

Species or Test-System (Pharmacological Data)

Sprague-Dawley rats

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

0.5 - 5 mg/kg

Method (Pharmacological Data)

in vivo; rats (230-350 g) anesthetized with a combination of α-chloralose, urethane and pentobarbital; 5-8 rats were treated b.i.d. with 0.5 or 5 mg/kg/dose title comp. for 3.5 days; rats received tyramine (Ty) (16 μg, i.v.) four times

Further Details (Pharmacological Data)

interaction of chronic title comp. with Ty; Ty inject. 1.5, 2, 2.5 and 3 h after last oral dose of title comp.; some rats tracheal intubated 2 h after treatment; mean arterial pressure (MAP), heart rate measured before and within 3O s after Ty admin.

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Results

under intact conditions, title comp. at 0.5 mg/kg 2 h after treatment markedly potentiated Ty peak MAP change and MAP AUC increase (diagrams); in tracheal intubated rats, effect of title comp. was lower (diagrams)

Humphrey, Stephen J.; Curry, James T.; Turman, Chauncey N.; Stryd, Ronald P.; Journal of Cardiovascular Pharmacology; vol. 37; nb. 5; (2001); p. 548 - 563, View in Reaxys 164 of 239 Effect (Pharmacological Data)

agonist

Species or Test-System (Pharmacological Data)

Sprague-Dawley rats

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

0.5 - 5 mg/kg

Method (Pharmacological Data)

in vivo; rats (230-350 g) anesthetized with a combination of α-chloralose, urethane and pentobarbital; 5-8 rats were treated b.i.d. with 0.5 or 5 mg/kg/dose title comp. or vehicle for 3.5 days; rats received metaraminol (MA) (2 μg, i.v.) four times

Further Details (Pharmacological Data)

interaction of chronic title comp. with MA; MA inject. 1.5, 2, 2.5 and 3 h after last oral dose of title comp.; some rats tracheal intubated 2 h after treatment; mean arterial pressure (MAP), heart rate measured before and within 3O s after Ty admin.

Comment (Pharmacological Data)

No effect

Humphrey, Stephen J.; Curry, James T.; Turman, Chauncey N.; Stryd, Ronald P.; Journal of Cardiovascular Pharmacology; vol. 37; nb. 5; (2001); p. 548 - 563, View in Reaxys 165 of 239 Effect (Pharmacological Data)

agonist

Species or Test-System (Pharmacological Data)

Sprague-Dawley rats

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

1.5 - 5 mg/kg

Method (Pharmacological Data)

in vivo; 5-8 rats (230-350 g) rats were treated acute (5 mg/kg) or chronic b.i.d. with 1.5 or 5.0 mg/kg/dose title comp. for 2.5 days; carotid artery cannulated under anesth.; rats received oral Ty (5 and 15 mg/kg) 1.5 or 2.0 h after treatment, resp.

Further Details (Pharmacological Data)

interaction of chronic title comp. with oral tyramine (Ty) in conscious rats; mean arterial pressure (MAP), heart rate measured before and within 3O s after Ty admin.

Results

title comp. given as single dose markedly potentiated oral Ty pressure response; chronic treatment resulted in Ty potentiation, at lower dose (1.5 mg/kg) was potentiating factor 2.8, at higher dose (5 mg/kg) factor was 1.8 (table)

Humphrey, Stephen J.; Curry, James T.; Turman, Chauncey N.; Stryd, Ronald P.; Journal of Cardiovascular Pharmacology; vol. 37; nb. 5; (2001); p. 548 - 563, View in Reaxys 166 of 239 Effect (Pharmacological Data)

agonist

Species or Test-System (Pharmacological Data)

Sprague-Dawley rats

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

1.5 mg/kg

Method (Pharmacological Data)

in vivo; 5-8 rats (230-350 g) rats were treated b.i.d. with 1.5 mg/kg/dose title comp. (1, 3 or 5 doses and 18-h of recovery); carotid artery cannulat. under anesth.; rats received oral tyramine (Ty) (5 and 15 mg/kg) 1.5 or 2.0 h after treatment, resp.

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Further Details (Pharmacological Data)

effect of treatment duration on title comp. potentiation of Ty; mean arterial pressure (MAP), heart rate measured before and within 3O s after Ty admin.

Results

title comp. maximally potentiated tyramine's pressor response after its first dose, remained stable through dose 5 adn returned to subcontrol at recovery (table)

Humphrey, Stephen J.; Curry, James T.; Turman, Chauncey N.; Stryd, Ronald P.; Journal of Cardiovascular Pharmacology; vol. 37; nb. 5; (2001); p. 548 - 563, View in Reaxys 167 of 239 Effect (Pharmacological Data)

agonist

Species or Test-System (Pharmacological Data)

Sprague-Dawley rats

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

5 mg/kg

Method (Pharmacological Data)

in vivo; 5-8 rats (230-350 g) rats were treated acute or chronic b.i.d. with 5 mg/kg/dose title comp. (1.5 or 2.5 days); carotid artery cannulat. under anesth.; rats p.o. received sympathomimetic amines 1.5 and 2.0 h after treatment

Further Details (Pharmacological Data)

effect of title comp. on sympathomimetic agents (SA); mean arterial pressure (MAP), heart rate measured before and within 3O s after SA admin.; sympathomimetic agents: pseudoephedrine, phenylpropanolamine, dextromethorphane or their combinations

Comment (Pharmacological Data)

No effect

Humphrey, Stephen J.; Curry, James T.; Turman, Chauncey N.; Stryd, Ronald P.; Journal of Cardiovascular Pharmacology; vol. 37; nb. 5; (2001); p. 548 - 563, View in Reaxys 168 of 239 Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

homo sapiens

Route of Application

peroral

Concentration (Pharmacological Data)

300 mg

Method (Pharmacological Data)

16 persons (20 - 36 years old), genotyped for CYP2C19 (extensive and poor metabolizers); single dose of omeprazole (40 mg) admin. for 8 days; on days 1 and 8 title comp. coadmin., then venous blood (O - 24 h) and urine (0 - 32 h) samples coll.; HPLC/UV

Further Details (Pharmacological Data)

placebo control (placebo for 8 days, on day 8 title comp. coadministered); effect of omeprazole on the pharmacokinetics of the title comp. according to the genetic polymorphism of CYP2C19 investigated; HPLC determ. of the title comp. conc.

Half-life Time (Pharmacological Data)

3.39 - 7.98 h

Results

pharmacokinetic param. of title comp. during treatment with omeprazole at extensive or poor CYP2C19 metabolizers (tmax, Cmax, AUC24, AUCinfinite, Vz/F, CL/F, CLR, MRT, fract. excreted unchanged) (table), mean plasma conc. (0 - 25 h) (diagram)

Yu, Kyung-Sang; Yim, Dong-Seok; Cho, Joo-Youn; Park, Soon Seong; Park, Ji Young; Lee, Kyung-Hoon; Jang, In-Jin; Yi, So-Young; Bae, Kyun-Seop; Shin, Sang-Goo; Clinical Pharmacology and Therapeutics; vol. 69; nb. 4; (2001); p. 266 - 273, View in Reaxys 169 of 239 Effect (Pharmacological Data)

receptor; binding activity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat striatal membranes

Sex

male

Concentration (Pharmacological Data)

1E-10 - 0.0001 mol/l

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Method (Pharmacological Data)

membranes were incubated with 6 nmol/l <3H>Ro 41-1049 and title comp. in Tris-buffer (pH 7.4) at 23 deg C for 4 h; BCA method

Further Details (Pharmacological Data)

Ki: binding affinity

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

33900 nmol/l

Levant, Beth; Morgan, Kimberly A.; Ahlgren-Beckendorf, Joy A.; Grandy, David K.; Chen, Kevin; Shih, Jean C.; Seif, Isabelle; Life Sciences; vol. 70; nb. 2; (2001); p. 229 - 241, View in Reaxys 170 of 239 Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

human

Sex

male and female

Route of Application

peroral

Concentration (Pharmacological Data)

150 mg

Kind of Dosing (Pharmacological Data)

with 150 ml water

Method (Pharmacological Data)

9 healthy volunteers were treated with title comp.; gastric decontamination performed 30 min later; blood venous samples collected before and 0.5-24 h after title comp. administration; plasma conc. of title comp. measured by HPLC

Further Details (Pharmacological Data)

gastric decontamination: 25 g activated charcoal in 200 ml water or gastric lavage; control: 200 ml water instead of decontamination; Cmax: peak plasma conc.; tmax: time to Cmax; AUC: the area under plasma concentration-time curve

Results

title comp. AUC0-24h was reduced to 44.7 percent of control by activated charcoal and to 56.5 percent of control by gastric lavage; Cmax was reduced to 60.2 percent and 64 percent (unsignificant) of control, resp.; tmax was not changed

Lapatto-Reiniluoto; Kivistoe; Neuvonen; European Journal of Clinical Pharmacology; vol. 56; nb. 4; (2000); p. 285 - 288, View in Reaxys 171 of 239 Effect (Pharmacological Data)

enzyme; inhib. of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat lung homogenate

Sex

male

Concentration (Pharmacological Data)

1E-06 - 0.001 mol/l

Method (Pharmacological Data)

homogenates preincubated with title comp. (20 min, 37 deg C); reaction started by <14C>serotonin; incubated (5 or 10 min); reaction stopped by 3 N HCl; serotonin deaminated metabolites extracted; radioactivity measured with LSS; MAO-A activity detd.

Further Details (Pharmacological Data)

LSS: liquid scintillation spectrometry; MAO-A: monoamine oxidase-A

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

11 μmol/l

Results

title comp. inhibited the ability of MAO-A to deaminate serotonin and the inhibition was concentration-dependent; table, figure

Ulus, Ismail H.; Maher, Timothy J.; Wurtman, Richard J.; Biochemical Pharmacology; vol. 59; nb. 12; (2000); p. 1611 - 1621, View in Reaxys 172 of 239 Effect (Pharmacological Data)

enzyme; inhib. of

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Species or Test-System (Pharmacological Data)

Sprague-Dawley rat liver homogenate

Sex

male

Concentration (Pharmacological Data)

1E-06 - 0.001 mol/l

Method (Pharmacological Data)

Further Details (Pharmacological Data)

LSS: liquid scintillation spectrometry; MAO-A: monoamine oxidase-A

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

10 μmol/l

Results

title comp. inhibited the ability of MAO-A to deaminate serotonin and the inhibition was concentration-dependent; table, figure

Ulus, Ismail H.; Maher, Timothy J.; Wurtman, Richard J.; Biochemical Pharmacology; vol. 59; nb. 12; (2000); p. 1611 - 1621, View in Reaxys 173 of 239 Effect (Pharmacological Data)

enzyme; inhib. of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat brain homogenate

Sex

male

Concentration (Pharmacological Data)

1E-06 - 0.001 mol/l

Method (Pharmacological Data)

Further Details (Pharmacological Data)

LSS: liquid scintillation spectrometry; MAO-A: monoamine oxidase-A

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

14 μmol/l

Results

title comp. inhibited the ability of MAO-A to deaminate serotonin and the inhibition was concentration-dependent; table, figure

Ulus, Ismail H.; Maher, Timothy J.; Wurtman, Richard J.; Biochemical Pharmacology; vol. 59; nb. 12; (2000); p. 1611 - 1621, View in Reaxys 174 of 239 Effect (Pharmacological Data)

enzyme; inhib. of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat lung homogenate

Sex

male

Concentration (Pharmacological Data)

Ca. 10 - 5000 μmol/l

Method (Pharmacological Data)

homogenates preincubated with title comp. (20 min, 37 deg C); reaction started by <14C>β-phenylethylamine; incubated (2 min); reaction stopped by 3 N HCl; deaminated metabolites extracted; radioactivity measured with LSS; MAO-B activity detd.

Further Details (Pharmacological Data)

LSS: liquid scintillation spectrometry; MAO-B: monoamine oxidase-B

Type (Pharmacological Data)

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Value of Type (Pharmacological Data)

1250 μmol/l

Results

title comp. inhibited ability of MAO-B to deaminate β-phenylethylamine and the inhibition was concentration-dependent; table, figure

Ulus, Ismail H.; Maher, Timothy J.; Wurtman, Richard J.; Biochemical Pharmacology; vol. 59; nb. 12; (2000); p. 1611 - 1621, View in Reaxys 175 of 239 Effect (Pharmacological Data)

enzyme; inhib. of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat liver homogenate

Sex

male

Concentration (Pharmacological Data)

Ca. 10 - 5000 μmol/l

Method (Pharmacological Data)

Further Details (Pharmacological Data)

LSS: liquid scintillation spectrometry; MAO-B: monoamine oxidase-B

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

1600 μmol/l

Results

title comp. inhibited ability of MAO-B to deaminate β-phenylethylamine and the inhibition was concentration-dependent; table, figure

Ulus, Ismail H.; Maher, Timothy J.; Wurtman, Richard J.; Biochemical Pharmacology; vol. 59; nb. 12; (2000); p. 1611 - 1621, View in Reaxys 176 of 239 Effect (Pharmacological Data)

enzyme; inhib. of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat brain homogenate

Sex

male

Concentration (Pharmacological Data)

Ca. 10 - 5000 μmol/l

Method (Pharmacological Data)

Further Details (Pharmacological Data)

LSS: liquid scintillation spectrometry; MAO-B: monoamine oxidase-B

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

1650 μmol/l

Results

title comp. inhibited ability of MAO-B to deaminate β-phenylethylamine and the inhibition was concentration-dependent; table, figure

Ulus, Ismail H.; Maher, Timothy J.; Wurtman, Richard J.; Biochemical Pharmacology; vol. 59; nb. 12; (2000); p. 1611 - 1621, View in Reaxys 177 of 239 Effect (Pharmacological Data)

toxicity, acute

Species or Test-System (Pharmacological Data)

ddY mice

Route of Application

peroral

Concentration (Pharmacological Data)

500 - 1000 mg/kg

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Kind of Dosing (Pharmacological Data)

title comp. suspended in 0.5 percent carboxymethylcellulose Na

Method (Pharmacological Data)

title comp. added, mortality and global behavior observed at 10, 30, 60, 120, 180 and 300 min after title comp. admin. and once daily for following 14 d

Results

title comp. at 500 mg/kg caused ataxia at 1 and hypomotility in 3 mice; at 1000 mg/kg dose produced convulsion in 1 mouse and hypomotility in the others but did not cause death

Kato, Masaya; Katayama, Taiichi; Iwata, Hiroshi; Yamamura, Michio; Matsuoka, Yuzo; Narita, Hiroshi; Journal of Pharmacology and Experimental Therapeutics; vol. 284; nb. 3; (1998); p. 983 - 990, View in Reaxys 178 of 239 Effect (Pharmacological Data)

antidepressant

Species or Test-System (Pharmacological Data)

CD-1 mice

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

100 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. suspended in 0.5 percent carboxymethylcellulose Na

Method (Pharmacological Data)

title comp. added 1 h before s.c. injection of oxotremorine (0.3 mg/kg), the effect of title comp. on the oxotremorine-induced tremor expressed as ED50, defined as the dose that antagonized tremor in 50 percent of the animals

Results

title comp. had no effect on oxotremorine-induced tremor even at 100 mg/kg

antidepressant

Species or Test-System (Pharmacological Data)

Wistar rats

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

30 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. suspended in 0.5 percent carboxymethylcellulose Na

Method (Pharmacological Data)

rats implanted with catether in common carothid artery, title comp. added, 5 mg/kg tyramine administered p.o. 1 h later, arterial blood pressure measured

Results

pretreatment with title comp. signif. and markedly potentiated the pressor response to tyramine (24.2 +/- 5.4 percent increase)

antidepressant

Species or Test-System (Pharmacological Data)

CD rat

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

<= 50 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. suspended in 0.5 percent carboxymethylcellulose Na

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Method (Pharmacological Data)

animals were stressed by electric shocks, trained to escape response, title comp. added six times in 4 d, escape failures measured compared with a control group

Results

stressed rats, those pretreated with inescapable shocks, exhibited significantly more escape failures than nonstressed control; title comp. showed the tendency to reverse the deficit, although the effect was not signif. up to 50 mg/kg

behavioural symptoms

Species or Test-System (Pharmacological Data)

ddY mice

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

30 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. suspended in 0.5 percent carboxymethylcellulose Na

Method (Pharmacological Data)

animals placed individually into a cylinder containing water, left there for 15 min, 18 h later test repeated, 1 h before the test title comp. added, total duration of immobility measured

Results

title comp. was inactive in this testat 30 mg/kg dose; minimal effective dose >30 mg/kg

antidepressant

Species or Test-System (Pharmacological Data)

CD-1 mice

Sex

male

Route of Application

peroral

Kind of Dosing (Pharmacological Data)

title comp. suspended in 0.5 percent carboxymethylcellulose Na

Method (Pharmacological Data)

title comp. added immediately after 5 mg/kg i.p. reserpine injection, hypothermia estimated by measuring the rectal temperature before and 4 h after reserpine treatment

Results

oral admin. of title comp. prevented reserpine-induced hypothermia; minimal effective dose 1 mg/kg

antidepressant

Species or Test-System (Pharmacological Data)

CD rat

Sex

male

Route of Application

peroral

Kind of Dosing (Pharmacological Data)

title comp. suspended in 0.5 percent carboxymethylcellulose Na

Method (Pharmacological Data)

title comp. added 1 h after 6 mg/kg i.p. reserpine injection, akinesia evaluated 2 h after reserpine treatment

Type (Pharmacological Data)

ED50

Value of Type (Pharmacological Data)

2.41 mg/kg

Results

oral admin. of title comp. prevented reserpine-induced akinesia

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antidepressant

Species or Test-System (Pharmacological Data)

CD-1 mice

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

1.49 - 3.87 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. suspended in 0.5 percent carboxymethylcellulose Na

Method (Pharmacological Data)

title comp. added immediately after 5 mg/kg i.p. reserpine injection, akinesia evaluated 2 h after reserpine treatment

Type (Pharmacological Data)

ED50

Value of Type (Pharmacological Data)

2.40 mg/kg

Results

oral admin. of title comp. potently prevented reserpine-induced akinesia

antidepressant

Species or Test-System (Pharmacological Data)

CD rat

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

2.52 - 5.3 mg/g

Kind of Dosing (Pharmacological Data)

title comp. suspended in 0.5 percent carboxymethylcellulose Na

Method (Pharmacological Data)

title comp. added 1 h after 6 mg/kg i.p. reserpine injection, ptosis evaluated 2 h after reserpine treatment

Type (Pharmacological Data)

ED50

Value of Type (Pharmacological Data)

3.54 mg/kg

Results

oral admin. of title comp. prevented reserpine-induced ptosis

antidepressant

Species or Test-System (Pharmacological Data)

CD-1 mice

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

2.82 - 6.93 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. suspended in 0.5 percent carboxymethylcellulose Na

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Method (Pharmacological Data)

title comp. added immediately after 5 mg/kg i.p. reserpine injection, ptosis evaluated 2 h after reserpine treatment

Type (Pharmacological Data)

ED50

Value of Type (Pharmacological Data)

4.23 mg/kg

Results

oral admin. of title comp. prevented reserpine-induced ptosis

antidepressant

Species or Test-System (Pharmacological Data)

CD-1 mice

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

11.1 - 27.2 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. suspended in 0.5 percent carboxymethylcellulose Na

Method (Pharmacological Data)

title comp. added 1 h before 150 mg/kg i.p. L-dopa injection, animals observed for the presence of behavioral excitation from 30 to 50 min after L-dopa treatment

Type (Pharmacological Data)

ED50

Value of Type (Pharmacological Data)

17.2 mg/kg

Results

oral admin. of title comp. potentiated the L-dopa-induced behavioral excitation

antidepressant

Species or Test-System (Pharmacological Data)

CD-1 mice

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

16.4 - 68.3 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. suspended in 0.5 percent carboxymethylcellulose Na

Method (Pharmacological Data)

title comp. added 70 min before 25 mg/kg i.p. β-phenylethylamine (PEA) injection, behavioral symptoms detected 20 to 30 min after the injection

Type (Pharmacological Data)

ED50

Value of Type (Pharmacological Data)

25.8 mg/kg

Results

p.o. admin. of title comp. potentiated the effect of PEA

antidepressant CD rat

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Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

1.27 - 2.64 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. suspended in 0.5 percent carboxymethylcellulose Na

Method (Pharmacological Data)

title comp. added 60 min before 100 mg/kg i.p. L-5-HTP injection, behavioral symptoms detected 30 to 40 min after the injection

Type (Pharmacological Data)

ED50

Value of Type (Pharmacological Data)

1.79 mg/kg

Results

oral admin. of title comp. potentiated the effect of L-5-HTP, the effect was less than those of T-794

antidepressant

Species or Test-System (Pharmacological Data)

CD-1 mice

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

1.69 - 2.88 mg/kg

Kind of Dosing (Pharmacological Data)

title comp. suspended in 0.5 percent carboxymethylcellulose Na

Method (Pharmacological Data)

title comp. added 60 min before 100 mg/kg i.p. L-5-HTP injection, behavioral symptoms detected 30 to 40 min after the injection

Type (Pharmacological Data)

ED50

Value of Type (Pharmacological Data)

2.17 mg/kg

Results

oral admin. of title comp. potentiated the effect of L-5-HTP,the effect was less than those of T-794

drug interaction

Species or Test-System (Pharmacological Data)

human

Sex

male and female

Route of Application

peroral

Concentration (Pharmacological Data)

300 - 600 mg

Kind of Dosing (Pharmacological Data)

300 mg title comp. on d 1 and 24

Exposure Period (Pharmacological Data)

24 d

Method (Pharmacological Data)

open, partly double-blind, randomized, placebo-controlled parallel study; fluoxetine administered on d 2-8 (40mg), on d 9-24 (20 mg); blood samples collected; adverse events recorded

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Results

number, intensity, type of adverse events did not change when moclobemide was added; no clinically relevant changes in safety parameters; multiple dosing of title comp, did not lead to excessive accumulation

in vivo (mice) antidepressant activity (Porsolt forced swimming test)

Ghanbarpour, Alireza; Hadizadeh, Farzin; Piri, Faride; Rashidi-Ranjbar, Parviz; Pharmaceutica Acta Helvetiae; vol. 72; nb. 2; (1997); p. 119 - 122, View in Reaxys 193 of 239 Effect (Pharmacological Data)

analgesic, other

Species or Test-System (Pharmacological Data)

white mice

Sex

male and female

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 mg/kg

Kind of Dosing (Pharmacological Data)

test comp. admin. via gastric tube 30 min before s.c. inject. of clonidine sol.; pain factor applied 30 min after clonidine inject.

Exposure Period (Pharmacological Data)

60 min

Method (Pharmacological Data)

mice weigh. 20-22 g; pain react.induc. by 1) i.p. inject. of 0.6 percent acetic acid sol. ("vinegar spasm"); 2) "hot plate" method; 3) "tail jerking" method (tail expos. for 20 sec to focus. light beam); in the pres. of clonidine (0.2 mg/kg)

Further Details (Pharmacological Data)

1) effect assess. by decrease in average number of spasms during 5 min after inject.; 2) effect assess. by the time mice quetly stayed on hot plate before licking hind paws or jump out; 3) increase in latent period of tail jerking reaction

Results

enhanced analgesic effect of clonidine in "vinegar spasm" and "hot plate" tests; no effect on clonidine activ. in "tail jerking" test

Andreeva; Golovina; Syubaev; Mashkovskii; Pharmaceutical Chemistry Journal; vol. 31; nb. 4; (1997); p. 166 167, View in Reaxys 194 of 239 Effect (Pharmacological Data)

enzyme; inhib. of

Species or Test-System (Pharmacological Data)

human brain

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

300 mg

Kind of Dosing (Pharmacological Data)

twice daily

Method (Pharmacological Data)

in vivo; binding of <11C>harmine to MAO-A detd. by PET in brain of 16 healthy volunteers (20-40 y) at spec. intervals before and after a 7-day treatment with title comp. or esuprone (800 mg once daily) or placebo; plasma levels detd.

Further Details (Pharmacological Data)

MAO-A: monoamine oxidase A; PET: positron emission tomography; randomized doubleblind placebo-controlled study; inhibition of <11C>harmine binding to brain MAO-A by title comp. studied

Results

PET showed high degree of binding of <11C>harmine to MAO-A before treatment, and marked and similar reduction of binding after treatment with title comp. or esuprone, but no change in placebo group, diagrams

Bergstroem; Westerberg; Nemeth; Traut; Gross; Greger; Mueller-Peltzer; Safer; Eckernaes; Grahner; Langstroem; European Journal of Clinical Pharmacology; vol. 52; nb. 2; (1997); p. 121 - 128, View in Reaxys

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195 of 239 Comment (Pharmacological Data)

antidepressant activity: 329.5 sec of immobility in the Porsolt forced swimming test (control 614.8); anxiolytic activity: 1.22 entries to the open arm (control 2.0), 29.22percent time spent in the open arm (control 48.50) (albino rats, i.p., 5 mg/kg)

Yesilada; Gokhan; Ozer; Vural; Erol; Farmaco; vol. 51; nb. 12; (1996); p. 775 - 780, View in Reaxys 196 of 239 Comment (Pharmacological Data)

acute toxicity (mice), LD50=503.7-671.6 mg/kg ip

Avramova, P. D.; Danchev, N. D.; Buyukliev, R. T.; European Journal of Medicinal Chemistry; vol. 31; nb. 11; (1996); p. 909 - 914, View in Reaxys 197 of 239 Comment (Pharmacological Data)

increasing effect on hexobarbital sleeping time (mice, in vivo, ip); not significant decreasing of locomotor activity (mice, in vivo); antidepressive activity (mice, in vivo)

Avramova, P. D.; Danchev, N. D.; Buyukliev, R. T.; European Journal of Medicinal Chemistry; vol. 31; nb. 11; (1996); p. 909 - 914, View in Reaxys 198 of 239 Effect (Pharmacological Data)

antidepressant

Endpoint of Effect (Pharmacological Data)

head shaking

Species or Test-System (Pharmacological Data)

white mongrel mice

Route of Application

peroral

Concentration (Pharmacological Data)

2.5 - 10 mg/kg

Method (Pharmacological Data)

animals injected with 5-oxytryptophane (5-OTP) at a dose of 50 mg/kg (i.p.); assessment of ability of test comp. to potentiate action of 5-OTP

Further Details (Pharmacological Data)

ED50 was determined as effective dose leading to enhanced head shaking in 50 percent of test animals

Type (Pharmacological Data)

ED50

Value of Type (Pharmacological Data)

2.2 - 2.8 mg/kg

Andreeva; Pharmaceutical Chemistry Journal; vol. 30; nb. 6; (1996); p. 359 - 360, View in Reaxys 199 of 239 Effect (Pharmacological Data)

antidepressant

Species or Test-System (Pharmacological Data)

white mongrel mice

Route of Application

peroral

Concentration (Pharmacological Data)

2.5 - 10 mg/kg

Method (Pharmacological Data)

main antidepressant tests: despare test, antireserpine effect (2.5 g reserpine/kg, i.p.), increase of hypothermia induced by L-DOPA (200 mg/kg, i.p.), decrease of hypothermia induced by tremorin (20 mg/kg, s.c.)

Further Details (Pharmacological Data)

enhanced effect of 5-OTP; absence of anticholinergic properties in tremorin hypothermia test

Andreeva; Pharmaceutical Chemistry Journal; vol. 30; nb. 6; (1996); p. 359 - 360, View in Reaxys 200 of 239 Effect (Pharmacological Data)

drug interaction

Species or Test-System (Pharmacological Data)

human

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

150 mg

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Method (Pharmacological Data)

randomized, single-dose, double-blind crossover study on 12 healthy subjects; study consisted of 4 days; between 2 study days washout period of at least 72 hours; at 45 min, 2 hours and 5 hours after drug intake performed exercise on bicycle ergometer

Further Details (Pharmacological Data)

title compound (TICO) coadministered with 200 mg entacapone; hemodynamics (heart rate, blood pressure, impedance cardiography) and plasma concentrations of catecholamines and their metabolites measured both at rest and during bicycle excercise

Results

coadministration not changed hemodynamic parameters and norepinephrine and epinephrine concentrations in plasma at rest or during exercise; decrease in plasma 3-methoxy-4-hydroxyphenylglycol content induced by TICO not potentiated by entacapone

Illi; Sundberg; Ojala-Karlsson; Scheinin; Gordin; Clinical Pharmacology and Therapeutics; vol. 59; nb. 4; (1996); p. 450 - 457, View in Reaxys 201 of 239 Effect (Pharmacological Data)

antagonist

Species or Test-System (Pharmacological Data)

human liver microsomes (HLM)

Concentration (Pharmacological Data)

0.1 - 100 μmol/l

Method (Pharmacological Data)

livers from kidney donors homogenized; HLM incub. in Na-phosphate buffer+NADPPHgenerating system with title comp.+10 μM clomipramine (CIP) (37 deg C; pH 7.4; 20 min)

Further Details (Pharmacological Data)

metabolites of CIP extracted, measured by HPLC; inhibition of metabolism of CIP (to 8hydroxylated CIP <8-OH-CIP>, N-desmethyl-CIP <DCIP>) studied; Ki (inhibitor constant) determined

Results

Ki, μM: 210 <DCIP>; amount of 8-OH-CIP unaffected

hypertensive

Species or Test-System (Pharmacological Data)

human

Sex

male and female

Concentration (Pharmacological Data)

200 mg

Kind of Dosing (Pharmacological Data)

twice daily for 14 days; on day 7 selegiline (5 mg, twice daily) added

Method (Pharmacological Data)

healthy subjects were treated with title comp.; tyramine (1 - 8 mg, i.v.) injected on days -1, 6 and 14; systolic blood pressure and diastoic blood pressure measured and heart rate determined

Further Details (Pharmacological Data)

title comp. as monoamine oxidase inhibitor

Results

title comp. enhanced tyramine pressor sensitivity 2.4- alone or 8.4-times in combination with selegiline (diagram)

Korn; Wagner; Moritz; Dingemanse; European Journal of Clinical Pharmacology; vol. 49; nb. 4; (1996); p. 273 278, View in Reaxys 203 of 239 Effect (Pharmacological Data)

behavioural symptoms

Species or Test-System (Pharmacological Data)

Charles River CD1 mouse

Sex

female

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

1 - 10 mg/kg

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Method (Pharmacological Data)

mice 60 d old, weighing 22-24 g; free access to food, tap water; temp. 21 deg C; relative humidity 50-60 percent; effect on anxiety, exploratory, locomotor activities; light-dark aversion test; open-field test; mice were administered 30 min before testing

Further Details (Pharmacological Data)

time in lit area, transitions, ambulation, rearing determination; one-way ANOVA; NewmanKeuls test

Results

results on diagram; at dose 1, 5 and 10 mg/kg significantly reduced aversive behavior for lit area; no increase in locomotor activity

De Angelis, Luisa; Naunyn-Schmiedeberg's Archives of Pharmacology; vol. 354; nb. 3; (1996); p. 379 - 383, View in Reaxys 204 of 239 Effect (Pharmacological Data)

enzyme; inhib. of

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat brain

Sex

male

Method (Pharmacological Data)

tissue homogenates were preincubated with TICO (2,5 and 10 nM for MAO-A and 200,600 and 1400 nM for MAO-B) at 37 deg C; then specific substrates (<14C>-5-HT for MAO-A and <14C>PEA for MAO-B) were added and incubated additionally

Further Details (Pharmacological Data)

radioactivity was measured by scintillation spectrometry; Ki values were determinated from Cheng Prusoff equation; MAO: monoamine oxidase; TICO:title compound; 5-HT: 5hydroxytryptamine; PEA: phenylethylamine

Results

Ki values were 11500 nm for MAO-A and >100000 nM for MAO-B inhibition

Curet, Olivier; Damoiseau, Gabrielle; Aubin, Nadine; Sontag, Nicole; Rovei, Vincenzo; Jarreau, Francois-Xavier; Journal of Pharmacology and Experimental Therapeutics; vol. 277; nb. 1; (1996); p. 253 - 264, View in Reaxys 205 of 239 Effect (Pharmacological Data)

hemodynamic

Species or Test-System (Pharmacological Data)

Sprague-Dawley rats

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

5 mg/kg

Kind of Dosing (Pharmacological Data)

30 min before tyramine

Method (Pharmacological Data)

arterial pressure was directly measured in conscious freely moving rats via cannulas implanted in carotid artery; tyramine hydrochloride (12 mg/kg p.o.) was administered in food preparation

Results

title compound did not affect increase in systolic blood pressure after tyramine

Caille, Dominique; Bergis, Olivier-Emmanuel; Fankhauser, Christine; Gardes, Arlette; Adam, Roselyne; Charieras, Thierry; Grosset, Alain; Rovei, Vincenzo; Jarreau, Francois-Xavier; Journal of Pharmacology and Experimental Therapeutics; vol. 277; nb. 1; (1996); p. 265 - 277, View in Reaxys 206 of 239 Effect (Pharmacological Data)

neuropharmacological

Species or Test-System (Pharmacological Data)

OF1 mice

Sex

male

Route of Application

peroral

Method (Pharmacological Data)

spontaneous motor activity, sedative or stimulant activity and anticholinergic activity were measured

Further Details (Pharmacological Data)

TICO: title compound

Results

TICO (3-100 mg/kg) induced dose-dependent hypomotility; did not induce lethality up to 400 mg/kg; had no noticeable effect on sleeping time induced by barbital; did not antagonize oxotremorin-induced hypothermia up to 100 mg/kg

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neuropharmacological

Species or Test-System (Pharmacological Data)

Sprague-Dawley rats

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

200 mg/kg

Method (Pharmacological Data)

behavioral and neurological changes were observed during 2 hr after title compund treatment; information on central and peripheral autonomic effects were noted as present or absent

Results

title compound induced mild central nervous system depression (i.e., passivity when handling and hypomotility)

neuropharmacological

Species or Test-System (Pharmacological Data)

Sprague-Dawley rats

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

2.5 - 10 mg/kg

Method (Pharmacological Data)

anxiolytic activity was assessed in elevated-plus maze test

Results

title compound at 10 mg/kg produced increase in percentage of open arm entries (from 19.3 percent control value to 30.0 percent); decreased total number of entries (from 11.8 to 8.8)

neuropharmacological

Species or Test-System (Pharmacological Data)

Sprague-Dawley rats

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

25 mg/kg

Method (Pharmacological Data)

rats were implanted with electrodes for ECoG and electromyogram recordings; sleep stages were recorded in periods of 10-sec duration and three main stages were analysed: wakefulness, REMS and NREMS

Further Details (Pharmacological Data)

REMS: rapid eye movement sleep; NREMS: nonrapid eye movement sleep; TICO: title compound

Results

TICO increased REMS latency from 100 min (predrug control) up to 306.8 min; REMS did not change significantly

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210 of 239 Effect (Pharmacological Data)

neuropharmacological

Species or Test-System (Pharmacological Data)

Sprague-dawley rats

Sex

male

Route of Application

peroral

Kind of Dosing (Pharmacological Data)

at 28, 5 and 1 hr before trial

Method (Pharmacological Data)

forced swimming test was performed; duration of immobility was measured during 5 min; activity of title compound was expressed as lowest dose (MED) producing significant decrease in duration of immobility

Results

MED = 7.5 mg/kg, effect at MED = -27 percent; maximum effect = -54 percent at 30 mg/kg

Effect (Pharmacological Data)

neuropharmacological

Species or Test-System (Pharmacological Data)

OF1 mice

Sex

male

Route of Application

peroral

Kind of Dosing (Pharmacological Data)

60 min before reserpine

Method (Pharmacological Data)

mice were treated with reserpine (2 mg/kg i.v.); palpebral ptosis and akinesia were quantified 60 min after, rectal temperature was measured 120 min after reserpine

Results

title compound prevented reserpine-induced hypothermia with ED50=1.4 mg/kg, ptosis with 1.4 mg/kg and akinesia with 0.79 mg/kg

neuropharmacological

Species or Test-System (Pharmacological Data)

OF1 mice

Sex

male

Route of Application

peroral

Kind of Dosing (Pharmacological Data)

60 min before PEA

Method (Pharmacological Data)

mice were treated with PEA (25 mg/kg i.p.); animals were scored for presence of stereotyped behavior (mouth movements and licking), 15 min after PEA injection

Further Details (Pharmacological Data)

PEA: phenylethylamine

Results

title compound potentiated PEA-induced stereotypies with ED50 = 1.8 mg/kg

neuropharmacological

Species or Test-System (Pharmacological Data)

OF1 mice

Sex

male

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Route of Application

peroral

Kind of Dosing (Pharmacological Data)

60 min before L-dopa

Method (Pharmacological Data)

mice were treated with L-dopa (150 mg/kg i.p.); 30 min later animals were scored for presence of rapid running, jumping movements, stereotypies or tremor

Results

title compound potentiated L-dopa-induced behavior with ED50 =0.71 mg/kg

neuropharmacological

Species or Test-System (Pharmacological Data)

OF1 mice

Sex

male

Route of Application

peroral

Kind of Dosing (Pharmacological Data)

60 min before L-5-HTP

Method (Pharmacological Data)

mice were treated with L-5-HTP (100 mg/kg i.p.); 30 min later generalized tremor was assessing using an all-or-none method

Further Details (Pharmacological Data)

L-5-HTP: L-5-hydroxytryptophane

Results

title compound potentiated L-5-HTP-induced tremor with ED50 =0.73 mg/kg

neuropharmacological

Species or Test-System (Pharmacological Data)

Sprague-Dawley rats

Sex

male

Kind of Dosing (Pharmacological Data)

p.o. and i.v. respectively, 60 min before L-5-HTP

Method (Pharmacological Data)

rats were tretaed with L-5-HTP (100 mg/kg i.p.); 30 min later generalized tremor was assessing using an all-or-none method

Further Details (Pharmacological Data)

L-5-HTP: L-5-hydroxytryptophane

Results

title compound potentiated L-5-HTP-induced tremor with ED50 =1.2 and 1.6 mg/kg at i.v. and p.o. treatment

enzyme; inhib. of

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

3 - 10 mg/kg

Method (Pharmacological Data)

ex vivo; title compound was adm. through a stomach tube to rats (8-9 weeks old); at 2 h after administration, rats were decapitated, brain was removed, homogenized, monoamine oxidase B (MAO-B) activity determined as the deamination rates of the enzyme

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Further Details (Pharmacological Data)

MAO-B activity was determined after single (1 day) and repeated (7 days) administration of title compound, using <14C>β-PEA hydrochloride, with a liquid scintillation counter

Results

title compound showed slight but significant inhibition of MAO-B (table given)

enzyme; inhib. of

Species or Test-System (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

3 - 10 mg/kg

Method (Pharmacological Data)

ex vivo; title compound was adm. through a stomach tube to rats (8-9 weeks old); at 2 h after administration, rats were decapitated, brain was removed, homogenized, monoamine oxidase A (MAO-A) activity determined as the deamination rates of the enzyme

Further Details (Pharmacological Data)

MAO-A activity was determined after single (1 day) and repeated (7 days) administration of title compound, using <14C>5-HT binoxalate after 10 min incubation, with a liquid scintillation counter

Results

title compound inhibited MAO-A in a dose-dependent manner (table given)

enzyme; inhib. of

Species or Test-System (Pharmacological Data)

ddy mice

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

3 - 100 mg/kg

Method (Pharmacological Data)

the in vivo monoamine oxidase B (MAO-B) inhibitory activity was measured; 30 mg/kg βPEA was administered s.c. 1 h after title compound administration, then spontaneous activity was measured for 30 min from 10 min after β-PEA inj.

Further Details (Pharmacological Data)

the motor activities of vehicle-treated animals were 738 (counts/30 min); diagram given

Results

title compound exhibited MAO-B inhibitory activity

enzyme; inhib. of

Species or Test-System (Pharmacological Data)

ddy mice

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

0.3 - 300 mg/kg

Method (Pharmacological Data)

the in vivo monoamine oxidase A (MAO-A) inhibitory activity was measured; 0.1 ml/10 g b. wt. 5-HTP (100 mg/kg) administered i.p. in distilled water 1 or 24 h after the administration of title compound

Further Details (Pharmacological Data)

at 0.3-1.0 mg/kg conc. time course was determined; the in vivo MAO-A inhibitory was evaluated by abduction of hindlimbs and tremors after 30 min or 24 h after 5-HTP adm.

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Results

title compound inhibited MAO-A activity after 1 h adm. at 0.3-10 mg/kg conc.; but after 24 h for this action required 300 mg/kg of title compound

enzyme; inhib. of

Species or Test-System (Pharmacological Data)

Wistar rat brain

Sex

male

Kind of Dosing (Pharmacological Data)

dissolved in 0.5 percent MC solution

Method (Pharmacological Data)

8-9 weeks old animals were decapitated, forebrains were homogenized in phosphate buffer (ph 7.4); preincubated for 10 min at 37 deg C with title compound, monoamine oxidase B (MAO-B) activity was determined using <14C>β-PEA hydrochloride

Further Details (Pharmacological Data)

deaminated metabolites were extracted (with n-heptane), radioactivity was counted with a liquid scintillation counter

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

650 μmol/l

enzyme; inhib. of

Species or Test-System (Pharmacological Data)

Wistar rat brain

Sex

male

Kind of Dosing (Pharmacological Data)

dissolved in 0.5 percent MC solution

Method (Pharmacological Data)

8-9 weeks old animals; were decapitated, forebrains were homogenized in phosphate buffer (ph 7.4); preincubated for 10 min at 37 deg C with title compound, monoamine oxidase A (MAO-A) activity was determined using <14C>5-HT binoxalate

Further Details (Pharmacological Data)

deaminated metabolites were extracted (with Et2O), radioactivity was counted with a liquid scintillation counter

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

430 μmol/l

toxicity

Species or Test-System (Pharmacological Data)

human

Sex

male and female

Route of Application

peroral

Concentration (Pharmacological Data)

300 mg

Kind of Dosing (Pharmacological Data)

300 mg b.i.d. (tablets of 150 mg) after breakfast or dinner

Method (Pharmacological Data)

day 1 - subjects received ephedrine HCl or placebo; day 2 - opposite assignment; days 3-9 - only title comp. given; day 10-11 - assignments of 1-2 days repeated plus title comp. ; AE were studied using observations, questioning and laboratory parameters

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Further Details (Pharmacological Data)

13 healthy white volunteers (19-36 years); AE: adverse events; ephedrine: two doses of 50 mg with a 4-h interval

Results

during title comp. alone treatment, insomnia and impaired concentration were commonest AE; in combination with ephedrine amount of AE increased (palpitations, headache and lightheadedness) (table); no significant changes in laboratory parameters

Dingemanse, Jasper; Guentert, Theodor; Gieschke, Ronald; Stabl, Max; Journal of Cardiovascular Pharmacology; vol. 28; nb. 6; (1996); p. 856 - 861, View in Reaxys 223 of 239 Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

human

Sex

male and female

Route of Application

peroral

Concentration (Pharmacological Data)

300 mg

Kind of Dosing (Pharmacological Data)

300 mg b.i.d. (tablets of 150 mg) after breakfast or dinner

Method (Pharmacological Data)

subjects received title comp. on days 1-8, on day 8 subjects received 50 mg ephedrine HCl or placebo; blood samples collected before and 2 h after drug intake on 10 d; plasma conc. of title comp. and metabolites (Ro 12-5637, Ro 12-8095) determined

Further Details (Pharmacological Data)

13 healthy white volunteers (19-36 years); ephedrine: two doses of 50 mg with a 4-h interval

Results

plasma conc. of title comp. 2 h after dose was 2877 μg/l, Ro 12-5637 236 μg/l, Ro 12-8095 905 μg/l; ephedrine had no significant influence on plasma conc. of title comp. and its metabolites (table)

Metabolite XRN (Pharmacological Data)

8920249; 8990040

Metabolite (Pharmacological Data)

Ro 12-5637; Ro 12-8095

Dingemanse, Jasper; Guentert, Theodor; Gieschke, Ronald; Stabl, Max; Journal of Cardiovascular Pharmacology; vol. 28; nb. 6; (1996); p. 856 - 861, View in Reaxys 224 of 239 Effect (Pharmacological Data)

drug interaction

Species or Test-System (Pharmacological Data)

human

Sex

male and female

Route of Application

peroral

Concentration (Pharmacological Data)

300 mg

Kind of Dosing (Pharmacological Data)

300 mg b.i.d. (tablets of 150 mg) after breakfast or dinner

Method (Pharmacological Data)

1 d - subjects received ephedrine (50 mg with 4-h interval) or placebo; 2 d - opposite assignment; 3-9 d - only title comp. given; 10-11 d - assignments of 1-2 d repeated plus title comp.; title comp. and ephedrine pharmacodynamic interaction determined

Further Details (Pharmacological Data)

pharmacodynamic interaction between title comp. and ephedrine quantified by calculation of area under effect-time curve (AUE) for systolic (SBP) and diastolic (DBP) blood pressure and heart rate (HR); 13 healthy white volunteers (19-36 years)

Results

title comp. potentiated effect of ephedrine by median factor of 3.2 for SBP, 3.8 for DBP, and 0.6 for HR (table)

Dingemanse, Jasper; Guentert, Theodor; Gieschke, Ronald; Stabl, Max; Journal of Cardiovascular Pharmacology; vol. 28; nb. 6; (1996); p. 856 - 861, View in Reaxys 225 of 239 Effect (Pharmacological Data)

cardiotoxic

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Species or Test-System (Pharmacological Data)

human

Sex

male and female

Route of Application

peroral

Concentration (Pharmacological Data)

300 mg

Kind of Dosing (Pharmacological Data)

300 mg b.i.d. (tablets of 150 mg) after breakfast or dinner

Method (Pharmacological Data)

day 1 - subjects received ephedrine HCl (two doses of 50 mg with 4-h interval) or placebo; day 2 - opposite assignment; day 3-9 - only title comp. given; day 10-11 - assignments of 1-2 days repeated plus title comp. ; ECG on 1, 2, 10 and 11 days studied

Further Details (Pharmacological Data)

13 healthy white volunteers (19-36 years)

Results

in combination ephedrine plus title comp., ECG of 1 patient showed inversion T waves on ECG but repeated ECG 4h later was normal; another patient on 11 day showed junctional rhythm and retrograde inverted P waves with normalization by following day

Dingemanse, Jasper; Guentert, Theodor; Gieschke, Ronald; Stabl, Max; Journal of Cardiovascular Pharmacology; vol. 28; nb. 6; (1996); p. 856 - 861, View in Reaxys 226 of 239 Effect (Pharmacological Data)

hypertensive

Species or Test-System (Pharmacological Data)

human

Sex

male and female

Route of Application

peroral

Concentration (Pharmacological Data)

300 mg

Kind of Dosing (Pharmacological Data)

300 mg b.i.d. (tablets of 150 mg) after breakfast or dinner

Method (Pharmacological Data)

day 1 - subjects received ephedrine HCl or placebo; day 2 - opposite assignment; day 3-9 - only title comp. given; day 10-11 - assignments of 1-2 days repeated plus title comp.; sitting SBP and DBP were recorded by automated device on 1, 2, 10, 11 days

Further Details (Pharmacological Data)

13 healthy white volunteers (19-36 years); SBP: systolic blood pressure; DBP: diastolic blood pressure; ephedrine: two doses of 50 mg with a 4-h interval

Results

title comp. did not influenced on SBP and DBP but in combination with ephedrine, title comp. potentiated effects of ephedrine on SBP and DBP (increasing) (figure)

Dingemanse, Jasper; Guentert, Theodor; Gieschke, Ronald; Stabl, Max; Journal of Cardiovascular Pharmacology; vol. 28; nb. 6; (1996); p. 856 - 861, View in Reaxys 227 of 239 Effect (Pharmacological Data)

chronotropic pos.

Species or Test-System (Pharmacological Data)

human

Sex

male and female

Route of Application

peroral

Concentration (Pharmacological Data)

300 mg

Kind of Dosing (Pharmacological Data)

300 mg b.i.d. (tablets of 150 mg) after breakfast or dinner

Method (Pharmacological Data)

day 1 - subjects received ephedrine HCl or placebo; day 2 - opposite assignment; day 3-9 - only title comp. given; day 10-11 - assignments of 1-2 days repeated plus title comp.; heart rate was measured on 1, 2, 10 and 11 days

Further Details (Pharmacological Data)

13 healthy white volunteers (19-36 years); ephedrine: two doses of 50 mg with 4-h interval

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Comment (Pharmacological Data)

No effect

Dingemanse, Jasper; Guentert, Theodor; Gieschke, Ronald; Stabl, Max; Journal of Cardiovascular Pharmacology; vol. 28; nb. 6; (1996); p. 856 - 861, View in Reaxys 228 of 239 Effect (Pharmacological Data)

receptor; binding activity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat striatal membranes

Sex

male

Concentration (Pharmacological Data)

1E-09 - 0.0001 mol/l

Method (Pharmacological Data)

rat striatal membranes were incubated with ca. 100 pmol/l <3H>spiperone and up to 11 concentrations of title compound at 23 deg C for 2 h

Further Details (Pharmacological Data)

nonspecific binding was determined in the presence of 1 μmol/l (+)-butaclamol; free and bound radioligand was separated by filtration, counted in a liquid scintillation counter

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

> 100000 nmol/l

Levant; Moehlenkamp; Morgan; Leonard; Cheng; The Journal of pharmacology and experimental therapeutics; vol. 278; nb. 1; (1996); p. 145 - 153, View in Reaxys 229 of 239 Effect (Pharmacological Data)

receptor; binding activity

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat striatal membranes

Sex

male

Concentration (Pharmacological Data)

1E-09 - 0.0001 mol/l

Method (Pharmacological Data)

rat striatal membranes were incubated with 2 nmol/l <3H>quinpirole (D2 dopamine receptor agonist) and various concentrations of title compound at 23 deg C for 4 h

Further Details (Pharmacological Data)

nonspecific binding was determined in the presence of 1 μmol/l spiperone; free and bound radioligand was separated by filtration, counted in a liquid scintillation counter

Type (Pharmacological Data)

Value of Type (Pharmacological Data)

18700 nmol/l

Levant; Moehlenkamp; Morgan; Leonard; Cheng; The Journal of pharmacology and experimental therapeutics; vol. 278; nb. 1; (1996); p. 145 - 153, View in Reaxys 230 of 239 Comment (Pharmacological Data)

in vitro monoamine oxidase-A (IC50: 3 μM) inhibition

Branca, Quirico; Jakob-Roetne, Roland; Kettler, Rolf; Roever, Stephan; Scalone, Michelangelo; Chimia; vol. 49; nb. 10; (1995); p. 381 - 385, View in Reaxys 231 of 239 Comment (Pharmacological Data)

ex vivo monoamine oxidase-A inhibition ED50(brain): 8.2 μmol/kg (rats, p.o.)

Branca, Quirico; Jakob-Roetne, Roland; Kettler, Rolf; Roever, Stephan; Scalone, Michelangelo; Chimia; vol. 49; nb. 10; (1995); p. 381 - 385, View in Reaxys 232 of 239 Effect (Pharmacological Data)

smoking cessation

Species or Test-System (Pharmacological Data)

human

Sex

male and female

Route of Application

peroral

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Concentration (Pharmacological Data)

200 - 400 mg/d

Kind of Dosing (Pharmacological Data)

400 mg/day title comp. for 2 months and 200 mg/day during the third month

Exposure Period (Pharmacological Data)

Method (Pharmacological Data)

88 highly dependent smokers; 21-65 y; 38-118 kg; 150-192 cm; randomized, double-blind, placebo-controlled, parallel-group study

Further Details (Pharmacological Data)

self-reported and biochemically verified (plasmacotinine levels, <20ng/ml) abstinence rate; platelet monoamine oxidase B activity; plasma 3,4-dihydroxyphenylglycol concentration

Results

higher abstinence rate; adverse effect: insomnia

Berlin, Ivan; Said, Sophie; Spreux-Varoquaux, Odile; Launay, Jean-Marie; Olivares, Robert; Millet, Veronique; Lecrubier, Yves; Puech, Alain J.; Clinical Pharmacology and Therapeutics; vol. 58; nb. 4; (1995); p. 444 - 452, View in Reaxys 233 of 239 Effect (Pharmacological Data)

calcium metabolism regulator

Species or Test-System (Pharmacological Data)

HIT-T15 cells from hamster insulinoma

Concentration (Pharmacological Data)

<= 100 μM

Method (Pharmacological Data)

transient transfection assay; HIT cells transfected with DNA construct containing four copies of rat somatostatine gene cAMP response element (CRE); for single cell measurement of Ca2+ HIT cells loaded with fura-2; membrane depolarization by 45 mM KCl

Comment (Pharmacological Data)

No effect

Schwaninger; Schoefl; Blume; Roessig; Knepel; Molecular Pharmacology; vol. 47; nb. 6; (1995); p. 1112 - 1118, View in Reaxys 234 of 239 Effect (Pharmacological Data)

gene transcription

Species or Test-System (Pharmacological Data)

HIT-T15 cells from hamster insulinoma

Concentration (Pharmacological Data)

<= 30 μM

Method (Pharmacological Data)

transient tranfection assay; HIT cells transfected with DNA construct containing four copies of rat somatostatin gene cAMP response element (CRE) and indicator (LUC); membrane depolarization stimulated by 45 mM KCl

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

> 30000 nM

Results

no effect on depolarization induced CRE-directed gene transcription

Schwaninger; Schoefl; Blume; Roessig; Knepel; Molecular Pharmacology; vol. 47; nb. 6; (1995); p. 1112 - 1118, View in Reaxys 235 of 239 Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

human

Sex

male and female

Route of Application

peroral

Concentration (Pharmacological Data)

300 mg

Kind of Dosing (Pharmacological Data)

single

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Method (Pharmacological Data)

15 healthy subjects (23-27 years), <8 extensive and 7 poor metabolizers of S-mephenytoin> all 15 extensive metabolizers of sparteine; moclobemide and metabolites in blood and urine by HPLC; median values

Half-life Time (Pharmacological Data)

1.8 - 4 h

Results

compared with extensive metabolizers of S-mephenytoin, poor metabolizers of S-mephenytoin had lower clearance (16.1 vs 43.2 l/h) and higher half-lives

Gram, Lars F.; Guentert, Theodor W.; Grange, Susan; Vistisen, Kirsten; Broesen, Kim; Clinical Pharmacology & Therapeutics (New York, NY, United States); vol. 57; nb. 6; (1995); p. 670 - 677, View in Reaxys 236 of 239 Effect (Pharmacological Data)

pharmacokinetics

Species or Test-System (Pharmacological Data)

human

Sex

male and female

Route of Application

peroral

Concentration (Pharmacological Data)

600 mg/day

Kind of Dosing (Pharmacological Data)

300 mg on day 1; 300 mg every 12 h from day 3 to day 10; on day 10 one 300 mg dose

Exposure Period (Pharmacological Data)

10 d

Method (Pharmacological Data)

15 healthy subjects (23-27 years), ,<8 extensive and 7 poor metabolizers of S-mephenytoin> all 15 extensive metabolizers of sparteine; moclobemide and metabolites in blood and urine by HPLC; median values

Half-life Time (Pharmacological Data)

2.7 - 5.1 h

Results

compared with extensive metabolizers of S-mephenytoin, poor metabolizers of S-mephenytoin had lower clearance (13.4 vs 22.1 l/h) and higher half-lives

releasing hormones

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat hippocampus

Sex

male

Route of Application

subcutaneous

Concentration (Pharmacological Data)

10 mg/kg/d

Exposure Period (Pharmacological Data)

21 d

Method (Pharmacological Data)

350-375 g rats; 1μM of nisoxetine present

Results

significant increase of the electrically evoked release of 3H-noradrenaline; 2-methyl-5-hydroxytryptamine concentration dependently enhances the evoked release of 3H-noradrenaline

Mongeau, Raymond; Montigny, Claude De; Blier, Pierre; European Journal of Pharmacology; vol. 271; (1994); p. 121 - 130, View in Reaxys 238 of 239 Comment (Pharmacological Data)

reversible MAO-A inhibitor without mortality and hepatotoxic effects after phenobarbitalpretreatment without loss of body weight and normal transaminase-, cholesterol- and APvalues; male SPF-bred Wistar albino rats

Schlappi; Arzneimittel-Forschung/Drug Research; vol. 35; nb. 5; (1985); p. 800 - 803, View in Reaxys 239 of 239 Comment (Pharmacological Data)

single-dose pharmacokinetics in 6 healthy male volunteers 34-50 years old at 50 mg p.o. or i.v.; elimination half-life t1/2β 1.06 h

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Raaflaub; Haefelfinger; Trautmann; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 1; (1984); p. 80 - 82, View in Reaxys Use (171) Use Pattern

Location

References

in combination with droxidopa for the treatment of orthostatic hypotension

Patent; CHELSEA THERAPEUTICS, INC.; WO2008/3028; (2008); (A2) English, View in Reaxys

reversible monoamineoxidase inhibitor

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

schizophrenia

Patent; CNS Response; US2005/96311; (2005); (A1) English, View in Reaxys; Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys; Patent; BIRDS PHARMA GMBH BEROLINA INNOVATIVE RESEARCH and DEVELOPMENT SERVICES; WO2007/93450; (2007); (A2) English, View in Reaxys; Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

schizoaffective disorders

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

mania

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

manic disorder

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

bipolar I disorder

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

bipolar II disorder

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

depression associated with bipolar disorders

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

unipolar depression

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

agitation

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

insomnia in Alzheimer's patients

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

psychosis in dementia

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

Parkinsonism

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

alcoholism

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

sleep disorders associated with alcohol abstention in alcoholics

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

substance-related disorders

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

generalized agitation

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

generalized anxiety

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

anxiety disorders

Patent; CNS Response; US2005/96311; (2005); (A1) English, View in Reaxys; Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

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anxiety neuroses

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

major depression

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

major depressive disorder

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

borderline personality disorder

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys; Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

post-traumatic stress disorder

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

primary insomnia

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

dementia

Patent; SHELDON, Leslie James; WO2005/53703; (2005); (A1) English, View in Reaxys; Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys; Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

anorexia nervosa

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

social phobia

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

manic-depressive psychoses

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

mood disorders

Patent; CNS Response; US2005/96311; (2005); (A1) English, View in Reaxys; Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

psychotic disorders

Patent; CNS Response; US2005/96311; (2005); (A1) English, View in Reaxys; Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

psychosis

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

obsessive-compulsive disorder

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys; Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

Diseases beneficially treated by antagonists of seratogenic 5HT1A receptors

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

Diseases beneficially treated by antagonists of seratogenic 5HT2 receptors

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

Diseases beneficially treated by dopaminergic D1 receptor

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

Diseases beneficially treated by dopaminergic D2 receptor

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

Diseases beneficially treated by histaminergic H1 receptors

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

Diseases beneficially treated by

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

84/94

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andrenergic α1 receptors Diseases beneficially treated by andrenergic α2 receptors

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

Antipsychotic agent

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

Neuroleptic agent

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

Diseases responsive to atypical antipsychotic agents

Patent; CONCERT PHARMACEUTICALS INC.; WO2008/66620; (2008); (A2) English, View in Reaxys

monoamine oxidase inhibitor (MAOI)

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys; Patent; Universitaetsklinikum Freiburg; EP1693062; (2006); (A2) English, View in Reaxys; Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys; Patent; THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK; WO2008/100727; (2008); (A2) English, View in Reaxys

in combination with glycine or its derivatives for treatment of obsessive-compulsive disorder

Patent; THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK; WO2008/100727; (2008); (A2) English, View in Reaxys

obsessive-compulsive spectrum disorder

Patent; THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK; WO2008/100727; (2008); (A2) English, View in Reaxys

mono-amine oxidase inhibitor

Patent; HAAS, Magali; US2008/103127; (2008); (A1) English, View in Reaxys

additional psychoactive medication in combination with 2-phenyl-1,2ethanediol monocarbomates and dicarbamates useful for treatment of disruptive behavior disorders (DBDs)

Patent; HAAS, Magali; US2008/103127; (2008); (A1) English, View in Reaxys

monoamine oxidase (MAO) inhibitor

Patent; CHELSEA THERAPEUTICS, INC.; WO2008/3028; (2008); (A2) English, View in Reaxys; Patent; Chelsea Therapeutics, Inc.; US2008/227830; (2008); (A1) English, View in Reaxys

neurally mediated hypotension (NMH) in combination with droxidopa

Patent; Chelsea Therapeutics, Inc.; US2008/227830; (2008); (A1) English, View in Reaxys

depression

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys; Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

Migraines

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

migraine with aura

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

migraine without aura

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

85/94

2016-07-25 15:01:51

basilar artery migraine

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

carotidynia

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

headache-free migraine

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

ophthalmoplegic migraine

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

retinal migraine

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

familial hemiplegic migraine

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

abdominal migraine

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

acephalgic migraine

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

status migraine

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

nausea

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

photophobia

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

lightheadedness

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

scalp tenderness

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

vomiting

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

photopsia

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

fortification spectra

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

paresthesias

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

vertigo

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

syncope

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

seizure

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

confusion of mind state

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

diarrhea

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

cluster headaches

Patent; OXFORD PHARMACEUTICAL SERVICES INC.; WO2007/38675; (2007); (A2) English, View in Reaxys

reversible inhibitor of monoamine oxidase (RIMA)

Patent; Bristol-Myers Squibb Company; US2007/93508; (2007); (A1) English, View in Reaxys

Addiction behavior

Patent; Rabinoff, Michael D; US2007/134169; (2007); (A1) English, View in Reaxys

Addiction to tobacco products

Patent; Rabinoff, Michael D; US2007/134169; (2007); (A1) English, View in Reaxys

86/94

2016-07-25 15:01:51

Addiction to alcohol

Patent; Rabinoff, Michael D; US2007/134169; (2007); (A1) English, View in Reaxys

dopamine deficiency diseases

Patent; BIRDS PHARMA GMBH BEROLINA INNOVATIVE RESEARCH and DEVELOPMENT SERVICES; WO2007/93450; (2007); (A2) English, View in Reaxys

diseases which are based on disrupted tyrosine transport or disrupted tyrosine decarboxylase

Patent; BIRDS PHARMA GMBH BEROLINA INNOVATIVE RESEARCH and DEVELOPMENT SERVICES; WO2007/93450; (2007); (A2) English, View in Reaxys

psychoses

Patent; BIRDS PHARMA GMBH BEROLINA INNOVATIVE RESEARCH and DEVELOPMENT SERVICES; WO2007/93450; (2007); (A2) English, View in Reaxys

Parkinson's disease

Patent; BIRDS PHARMA GMBH BEROLINA INNOVATIVE RESEARCH and DEVELOPMENT SERVICES; WO2007/93450; (2007); (A2) English, View in Reaxys

restless leg syndrome

Patent; BIRDS PHARMA GMBH BEROLINA INNOVATIVE RESEARCH and DEVELOPMENT SERVICES; WO2007/93450; (2007); (A2) English, View in Reaxys

dystonia

Patent; BIRDS PHARMA GMBH BEROLINA INNOVATIVE RESEARCH and DEVELOPMENT SERVICES; WO2007/93450; (2007); (A2) English, View in Reaxys

inhibition of prolactin secretion

Patent; BIRDS PHARMA GMBH BEROLINA INNOVATIVE RESEARCH and DEVELOPMENT SERVICES; WO2007/93450; (2007); (A2) English, View in Reaxys

stimulation of the release of growth hormone

Patent; BIRDS PHARMA GMBH BEROLINA INNOVATIVE RESEARCH and DEVELOPMENT SERVICES; WO2007/93450; (2007); (A2) English, View in Reaxys

neurological symptoms of chronic manganese intoxications

Patent; BIRDS PHARMA GMBH BEROLINA INNOVATIVE RESEARCH and DEVELOPMENT SERVICES; WO2007/93450; (2007); (A2) English, View in Reaxys

amyotrophic lateral sclerosis

Patent; BIRDS PHARMA GMBH BEROLINA INNOVATIVE RESEARCH and DEVELOPMENT SERVICES; WO2007/93450; (2007); (A2) English, View in Reaxys

multiple system atrophy

Patent; BIRDS PHARMA GMBH BEROLINA INNOVATIVE RESEARCH and DEVELOPMENT SERVICES; WO2007/93450; (2007); (A2) English, View in Reaxys

acute psychoses with negative symptomatology

Patent; BIRDS PHARMA GMBH BEROLINA INNOVATIVE RESEARCH and DEVELOPMENT SERVICES; WO2007/93450; (2007); (A2) English, View in Reaxys

acute psychoses

Patent; BIRDS PHARMA GMBH BEROLINA INNOVATIVE RESEARCH and DEVELOPMENT SERVICES; WO2007/93450; (2007); (A2) English, View in Reaxys

monoamine oxidase inhibitor

Patent; CNS Response; US2005/96311; (2005); (A1) English, View in Reaxys; Patent; KYOWA HAKKO KOGYO CO., LTD.; EP1655029; (2006); (A1) English, View in Reaxys; Patent; BIRDS PHARMA GMBH BEROLINA INNOVATIVE RESEARCH and DEVELOPMENT SERVICES; WO2007/93450; (2007); (A2) English, View in Reaxys; Patent; SEED, John, C.; WO2005/51297; (2005); (A2) English, View in Reaxys

mono-amine oxidase inhibitor

Page/Page column 3-4; 28

Patent; Smith-Swintosky, Virginia L.; Reitz, Allen B.; US2007/155827; (2007); (A1) English, View in Reaxys

depression

Page/Page column 3-4; 28

Patent; Smith-Swintosky, Virginia L.; Reitz, Allen B.; US2007/155827; (2007); (A1) English, View in Reaxys

dysthymia

Patent; SHELDON, Leslie James; WO2005/53703; (2005); (A1) English, View in Reaxys; Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

bipolar disorder

Patent; SHELDON, Leslie James; WO2005/53703; (2005); (A1) English, View in Reaxys; Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

A composition for treating or reducing a cognitive and/or psychological disorders

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

87/94

2016-07-25 15:01:51

a cognitive disorder

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

an affective disorder

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

a neurobiological disorder

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

a substance abuse disorder

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

age-related memory loss

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

mild cognitive impairment

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

dementia is caused by or associated with Alzheimer Disease

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

dementia is caused by or associated with Parkinson's Disease

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

dementia is caused by or associated with Creutzfeldt-Jakob Disease

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

dementia is caused by or associated with Huntington's Disease

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

dementia is caused by or associated with Pick's Disease

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

dementia is caused by or associated with human immunodeficiency virus (HIV) infection

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

dementia is caused by or associated with autoimmune deficiency syndrome (AIDS)

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

dementia is caused by or associated with head trauma

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

cyclothymia

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

schizoaffective disorder

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

panic disorder

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

a social phobia

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

88/94

2016-07-25 15:01:51

bulimia

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

narcolepsy

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

treatment-related depression

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

attention deficit disorder

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

substance abuse disorder is characterized by an abuse of or dependence on a substance selected from a depressant, an anxiolytic, a stimulant, a hallucinogen, and a solvent

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys

reversible inhibitor of monoamine oxidase

Patent; Ewing, William R.; Zhu, Yeheng; Ellsworth, Bruce A.; US2006/287323; (2006); (A1) English, View in Reaxys

Anti-depressant

Patent; Ewing, William R.; Zhu, Yeheng; Ellsworth, Bruce A.; US2006/287323; (2006); (A1) English, View in Reaxys

Antidepressant

Patent; Renshaw, Perry F.; Cohen, Bruce M.; US2006/39890; (2006); (A1) English, View in Reaxys; Patent; SEED, John, C.; WO2005/51297; (2005); (A2) English, View in Reaxys

monoamine oxidase inhibitor

Page/Page column 4; 104

Patent; Maddaford, Shawn; Ramnauth, Jailall; Rakhit, Suman; Patman, Joanne; Renton, Paul; Annedi, Subhash C.; US2006/258721; (2006); (A1) English, View in Reaxys

antidepressant

Page/Page column 4; 104

Patent; Maddaford, Shawn; Ramnauth, Jailall; Rakhit, Suman; Patman, Joanne; Renton, Paul; Annedi, Subhash C.; US2006/258721; (2006); (A1) English, View in Reaxys

in combination with compounds having NOS inhibitory activity

Page/Page column 4; 104

Patent; Maddaford, Shawn; Ramnauth, Jailall; Rakhit, Suman; Patman, Joanne; Renton, Paul; Annedi, Subhash C.; US2006/258721; (2006); (A1) English, View in Reaxys

anti-depressant agent

Patent; Pendri, Annapurna; Gerritz, Samuel; Dodd, Dharmpal S.; Sun, Chongqing; US2005/80087; (2005); (A1) English, View in Reaxys

Additive component (third drug) of pharmaceutical formulations of methods of treatment of nervous system disorders

Patent; CNS Response; US2005/96311; (2005); (A1) English, View in Reaxys

childhood disorders

Patent; CNS Response; US2005/96311; (2005); (A1) English, View in Reaxys

cognitive disorders

Patent; CNS Response; US2005/96311; (2005); (A1) English, View in Reaxys

substance disorders

Patent; CNS Response; US2005/96311; (2005); (A1) English, View in Reaxys

somatoform disorders

Patent; CNS Response; US2005/96311; (2005); (A1) English, View in Reaxys

factitious disorders

Patent; CNS Response; US2005/96311; (2005); (A1) English, View in Reaxys

89/94

2016-07-25 15:01:51

dissociative disorders

Patent; CNS Response; US2005/96311; (2005); (A1) English, View in Reaxys

sexual disorders

Patent; CNS Response; US2005/96311; (2005); (A1) English, View in Reaxys

gender identity disorders

Patent; CNS Response; US2005/96311; (2005); (A1) English, View in Reaxys

eating disorders

Patent; CNS Response; US2005/96311; (2005); (A1) English, View in Reaxys

sleep disorders

Patent; CNS Response; US2005/96311; (2005); (A1) English, View in Reaxys

impulse-control disorders

Patent; CNS Response; US2005/96311; (2005); (A1) English, View in Reaxys

adjustment disorders

Patent; CNS Response; US2005/96311; (2005); (A1) English, View in Reaxys

personality disorders

Patent; CNS Response; US2005/96311; (2005); (A1) English, View in Reaxys

selective MAO A inhibitor; inhibit isoenzyme A of monoamine oxidase

Patent; SHELDON, Leslie James; WO2005/53703; (2005); (A1) English, View in Reaxys

psychiatric disorders

Patent; SHELDON, Leslie James; WO2005/53703; (2005); (A1) English, View in Reaxys

neurodegenerative disorder

Patent; SHELDON, Leslie James; WO2005/53703; (2005); (A1) English, View in Reaxys

cortical dementia

Patent; SHELDON, Leslie James; WO2005/53703; (2005); (A1) English, View in Reaxys

fronto-temporal dementia

Patent; SHELDON, Leslie James; WO2005/53703; (2005); (A1) English, View in Reaxys

Alzheimer's dementia

Patent; SHELDON, Leslie James; WO2005/53703; (2005); (A1) English, View in Reaxys

lewy body dementia

Patent; SHELDON, Leslie James; WO2005/53703; (2005); (A1) English, View in Reaxys

progressive dementia

Patent; SHELDON, Leslie James; WO2005/53703; (2005); (A1) English, View in Reaxys

vascular dementia

Patent; SHELDON, Leslie James; WO2005/53703; (2005); (A1) English, View in Reaxys

multi-infarct dementia

Patent; SHELDON, Leslie James; WO2005/53703; (2005); (A1) English, View in Reaxys

drug-or alcoholrelated dementia

Patent; SHELDON, Leslie James; WO2005/53703; (2005); (A1) English, View in Reaxys

Parkinson's-related dementia

Patent; SHELDON, Leslie James; WO2005/53703; (2005); (A1) English, View in Reaxys

depressive disorders

Patent; SHELDON, Leslie James; WO2005/53703; (2005); (A1) English, View in Reaxys

unipolar or major depression

Patent; SHELDON, Leslie James; WO2005/53703; (2005); (A1) English, View in Reaxys

behavioral disorder

Patent; SHELDON, Leslie James; WO2005/53703; (2005); (A1) English, View in Reaxys

apathy

Patent; SHELDON, Leslie James; WO2005/53703; (2005); (A1) English, View in Reaxys

Obesity

Patent; SEED, John, C.; WO2005/51297; (2005); (A2) English, View in Reaxys

Achieving desirable weight loss

Patent; SEED, John, C.; WO2005/51297; (2005); (A2) English, View in Reaxys

Overweight

Patent; SEED, John, C.; WO2005/51297; (2005); (A2) English, View in Reaxys

90/94

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Preventing undesirable weight gain

Patent; SEED, John, C.; WO2005/51297; (2005); (A2) English, View in Reaxys

Reducing body weight

Patent; SEED, John, C.; WO2005/51297; (2005); (A2) English, View in Reaxys

Maintaining stable weight

Patent; SEED, John, C.; WO2005/51297; (2005); (A2) English, View in Reaxys

Depression

Patent; SEED, John, C.; WO2005/51297; (2005); (A2) English, View in Reaxys

Alzheimer's disease

Patent; SEED, John, C.; WO2005/51297; (2005); (A2) English, View in Reaxys

Monoamine oxidase inhibitor

Patent; Palatin Technologies, Inc.; US2004/224957; (2004); (A1) English, View in Reaxys

antidepressant

Andreeva; Pharmaceutical Chemistry Journal; vol. 30; nb. 6; (1996); p. 359 - 360, View in Reaxys

Reaxys ID 26931104 View in Reaxys

3/6

O 13C

CAS Registry Number: 1622398-86-0 Chemical Name: [13C]-moclobemide; [13C]-4-chloro-N-(2-morpholinoethyl)benzamide Linear Structure Formula: C12 (13)CH17ClN2O2 Molecular Formula: C13H17ClN2O2 Molecular Weight: 269.732 InChI Key: YHXISWVBGDMDLQ-KCKQSJSWSA-N Note:

O N H

Substance Label (1) Label References 4b

Crystal Property Description (1) Colour & Other Location Properties colourless

supporting information

References Lescot, Camille; Nielsen, Dennis U.; Makarov, Ilya S.; Lindhardt, Anders T.; Daasbjerg, Kim; Skrydstrup, Troels; Journal of the American Chemical Society; vol. 136; nb. 16; (2014); p. 6142 - 6147, View in Reaxys

NMR Spectroscopy (2) 1 of 2

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

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

400

Location

supporting information

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

13C

Solvents (NMR Spectro- chloroform-d1 scopy)

91/94

2016-07-25 15:01:51

Frequency (NMR Spectroscopy) [MHz]

100

Location

supporting information

References

high resolution supporting informass spectrome- mation try (HRMS); spectrum

Reaxys ID 8151826 View in Reaxys

4/6 Chemical Name: <(14)C>moclobemide Linear Structure Formula: C12 (14)CH17ClN2O2 Molecular Formula: C13H17ClN2O2 Molecular Weight: 270.732 Type of Substance: heterocyclic InChI Key: YHXISWVBGDMDLQ-ALWQSETLSA-N Note:

Cl O

14C

N O

Pharmacological Data (3) 1 of 3

Comment (Pharmacological Data)

Bioactivities present

De Sousa; Florence; Valles; Coassolo; Rahmani; Cell Biology and Toxicology; vol. 11; nb. 3-4; (1995); p. 147 153, View in Reaxys 2 of 3

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

human hepatocytes

Concentration (Pharmacological Data)

100 μmol/l

Exposure Period (Pharmacological Data)

24 h

Method (Pharmacological Data)

in vitro incubation of hepatocytes in primary culture with the (14)C-labelled drug; washing hepatocyte monolayer; scrapping off; radioactivity counting in extra- and intracellular fluids by β liquid scintillation; radio-HPLC analysis

Further Details (Pharmacological Data)

cells from liver biopsies resected from secondary tumors; Ham F12 medium suppl. with 10 percent DMSO and 20 percent FCS; in collagen I-coated Petri dishes; 37 deg C; humidified 5 percent CO2

Results

metabolizing 25 nmol from initial 100 nmol of the drug within 24 h; formation of metabolites: ClC6H4CONHCH2CH2NH2 (trace amounts) and ClC6H4CONHCH2CH2NHCH2CH2OH (ca. 1.5 nmol)

De Sousa; Florence; Valles; Coassolo; Rahmani; Cell Biology and Toxicology; vol. 11; nb. 3-4; (1995); p. 147 153, View in Reaxys 3 of 3

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat hepatocytes

Concentration (Pharmacological Data)

100 μmol/l

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Exposure Period (Pharmacological Data)

24 h

Method (Pharmacological Data)

Further Details (Pharmacological Data)

William's E medium + 50 U/ml penicillin, 50 μg/ml streptomycin, 50 μg/ml netilmycin, 0.1U/ml insulin and hydrocortisone hemisuccinate; in collagen I-coated Petri dishes; 37 deg C; humidified 5 percent CO2 atmosphere

Results

metabolizing 78 nmol from initial 100 nmol of the drug within 24 h; formation of metabolites: ClC6H4CONHCH2CH2NH2 (1.6 nmol) and ClC6H4CONHCH2CH2NHCH2CH2OH (ca. 12.5 nmol)

De Sousa; Florence; Valles; Coassolo; Rahmani; Cell Biology and Toxicology; vol. 11; nb. 3-4; (1995); p. 147 153, View in Reaxys

Reaxys ID 4086195 View in Reaxys

5/6 Chemical Name: p-chloro-N-(2-morpholinoethyl)-benzamide hydrochloride; p-Chlor-N-(2-morpholinoethyl)benzamid,Hydrochlorid Linear Structure Formula: C13H17ClN2O2*ClH Molecular Formula: C13H17ClN2O2*ClH Molecular Weight: 305.204 Type of Substance: heterocyclic InChI Key: KWZZINAWJBIANG-UHFFFAOYSA-N Note:

Cl O NH

N Cl

Substance Label (1) Label References 1-15

Patent; Hoffmann-LaRoche; DE2706179; (1977); Chem.Abstr.; vol. 88; nb. 121196, View in Reaxys

Melting Point (1) 1 of 1

Melting Point [°C]

207 - 208

Patent; Hoffmann-LaRoche; DE2706179; (1977); Chem.Abstr.; vol. 88; nb. 121196, View in Reaxys

Reaxys ID 5687987 View in Reaxys Cl

6/6 CAS Registry Number: 108375-13-9 Chemical Name: p-chloro-N-(2-ethylmorpholinium)-benzamide chloride monohydrate Linear Structure Formula: C13H17ClN2O2*ClH*H2O Molecular Formula: C13H17ClN2O2*ClH*H2O Molecular Weight: 323.219 Type of Substance: heterocyclic InChI Key: YQOSVBGQFVVYOO-UHFFFAOYSA-N Note:

H Cl

O NH

N H

Density (1) 1 of 1

Density [g·cm-3]

1.37

Type (Density)

crystallographic

Durant; Van der Brempt; Bufkens; Evrard; Bulletin des Societes Chimiques Belges; vol. 95; nb. 2; (1986); p. 103 104, View in Reaxys Crystal Phase (2) Description (Crys- Comment (Crystal References tal Phase) Phase) Crystal structure determination

β=95.8 grad, a=13.5 Angstroem, b=15.81

Durant; Van der Brempt; Bufkens; Evrard; Bulletin des Societes Chimiques Belges; vol. 95; nb. 2; (1986); p. 103 - 104, View in Reaxys

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Angstroem, c=7.37 Angstroem, n=4.; Temperature: 293 K. Method of determination: X-ray Diffraction Interplanar spacing

Durant; Van der Brempt; Bufkens; Evrard; Bulletin des Societes Chimiques Belges; vol. 95; nb. 2; (1986); p. 103 - 104, View in Reaxys

Crystal System (1) Crystal System References monoclinic

Durant; Van der Brempt; Bufkens; Evrard; Bulletin des Societes Chimiques Belges; vol. 95; nb. 2; (1986); p. 103 - 104, View in Reaxys

Interatomic Distances and Angles (1) Description References Interatomic distances and angles Space Group (1) Space Group 14

Durant; Van der Brempt; Bufkens; Evrard; Bulletin des Societes Chimiques Belges; vol. 95; nb. 2; (1986); p. 103 - 104, View in Reaxys

References Durant; Van der Brempt; Bufkens; Evrard; Bulletin des Societes Chimiques Belges; vol. 95; nb. 2; (1986); p. 103 - 104, View in Reaxys

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