The inhibition of monoamine oxidase activity by various antidepressants: differences found in various mammalian species.
The effects of the antidepressant drugs zimeldine, imipramine, maprotiline or nomifensine on mitochondrial monoamine oxidase (MAO) activity in mouse, rat, dog and monkey brains were compared in vitro. Mouse, rat, dog and monkey brain MAO-B activities were inhibited by zimeldine more potently than MAO-A activity. Imipramine inhibited MAO-B more potently than MAO-A activity in mouse and rat brains. When dog and monkey brains were investigated, MAO-A activity was inhibited more potently than MAO-B activity at high concentrations of imipramine, while at low concentrations, MAO-B activity was more potently inhibited. Maprotiline and nomifensine inhibited mouse and rat brain MAO-B activity more potently than MAO-A activity, while the inverse was true for dog and monkey brains. All four drugs are competitive inhibitors of MAO-A, but noncompetitive inhibitors of MAO-B in all animal brains. The respective Ki values of these reagents for monkey brain MAO-A and MAO-B were low compared to those of mouse, rat and dog. These results indicate that monkey brain MAOs are more sensitive to antidepressant drugs than those in rodent brain.
Egashira
T
T
Department of Pharmacology, Oita Medical University, Japan.
Takayama
F
F
Yamanaka
Y
Y
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D004285:Dogs; D007099:Imipramine / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008251:Macaca; D008297:Male; D008376:Maprotiline / Q000494:pharmacology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009627:Nomifensine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D015031:Zimeldine / Q000494:pharmacology
D000928:Antidepressive Agents; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D009627:Nomifensine; D008376:Maprotiline; D015031:Zimeldine; D008995:Monoamine Oxidase; D007099:Imipramine