Interaction of psychotropic drugs with monoamine oxidase in rat brain.
Literature observations indicate that some psychotropic drugs may have inhibitory activity towards monoamine oxidase (MAO). This study was undertaken to assess the potency, isozyme selectivity and mechanism of inhibition of representative first- and second-generation antidepressant drugs towards rat brain MAO-A and MAO-B. Five tricyclic antidepressants (imipramine, trimipramine, clomipramine, amitriptyline and doxepine) and three selective serotonin reuptake inhibitors (fluoxetine, fluvoxamine and citalopram) were examined. They showed inhibitory activity towards MAO-A and MAO-B, with clear selectivity for MAO-B (Ki in the micromolar range). Their mechanism of inhibition was competitive towards MAO-B and of a mixed competitive type towards MAO-A. The results suggest that some of the drugs examined might also contribute an MAO inhibitory effect in chronically treated patients.
Gnerre
C
C
Institut de Chimie Thérapeutique, Ecole de Pharmacie, Université de Lausanne, Lausanne-Dorigny, Switzerland.
Kosel
M
M
Baumann
P
P
Carrupt
P A
PA
Testa
B
B
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D004347:Drug Interactions; D007527:Isoenzymes / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D011619:Psychotropic Drugs / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D007527:Isoenzymes; D008995:Monoamine Oxidase; D008996:Monoamine Oxidase Inhibitors; D011619:Psychotropic Drugs; D017367:Selective Serotonin Reuptake Inhibitors