The advent of a new generation of monoamine oxidase inhibitor antidepressants: pharmacologic studies with moclobemide and brofaromine.

Severe side effects such as hepatotoxicity and potentiation of the sympathomimetic action of tyramine ("the cheese effect") caused the withdrawal of nonselective irreversible monoamine oxidase (MAO) inhibitors from use in psychiatric therapy. The development of selective irreversible 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," selective reversible MAO-A inhibitor antidepressants such as moclobemide and brofaromine have been developed. Being reversibly bound to MAO, these drugs may be displaced from their binding site in the intestine by ingested, indirectly sympathomimetic amines such as tyramine, thus avoiding the initiation of the hypertensive crises. Using a rat renal nerve preparation, we have demonstrated that acute administration of either moclobemide or brofaromine (10 mg/kg) does not cause a decrease in 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.