THE ADVENT OF A NEW-GENERATION OF MONOAMINE-OXIDASE INHIBITOR ANTIDEPRESSANTS - PHARMACOLOGICAL STUDIES WITH MOCLOBEMIDE AND BROFAROMINE

Severe side effects such as hepatotoxicity and potentiation of the sym pathomimetic action of tyramine (''the cheese effect'') caused the wit hdrawal of nonselective irreversible monoamine oxidase (MAO) inhibitor s from use in psychiatric therapy. The development of selective irreve rsible inhibitors for MAO type A did not eliminate cardiovascular side effects such as ''the cheese effect'' or, conversely, the hypotensive effect of these drugs. To overcome at least ''the cheese effect,'' se lective reversible MAO-A inhibitor antidepressants such as moclobemide and brofaromine have been developed. Being reversibly bound to MAO, t hese drugs may be displaced from their binding site in the intestine b y ingested, indirectly sympathomimetic amines such as tyramine, thus a voiding the initiation of the hypertensive crises. Using a rat renal n erve preparation, we have demonstrated that acute administration of ei ther moclobemide or brofaromine (10 mg/kg) does not cause a decrease i n blood pressure or a significant reduction in sympathetic renal nerve activity. These data contrast with those obtained with clorgyline or desipramine. The results indicate that moclobemide and brofaromine may be devoid of a hypotensive effect, including orthostatic hypotension.