Toru Egashira, Fusako Takayama and Yasumitsu Yamanaka
Department of Pharmacology, Oita Medical University, 1 - 1, Idaigaoka,
Hasama-machi, Oita 879 - 5593, Japan
Abstract: 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.
Keywords: Antidepressant, Animal species, Monoamine oxidase A, Monoamine
oxidase B, Brain