Advances Pertaining to the Pharmacology and Interactions of Irreversible Nonselective Monoamine Oxidase Inhibitors

Recent advances clarifying the pharmacology and interactions of irreversible nonselective monoamine oxidase inhibitors that have not been considered in depth lately are discussed. These new data elucidate aspects of enzyme inhibition and pharmacokinetic interactions involving amine oxidases, cytochrome P450 enzymes, aminotransferases (transaminases), and decarboxylases (carboxy-lyases) and the effects of tyramine. Phenelzine and tranylcypromine remain widely available, and many publications have data relevant to this review. Their effect on CYP 450 enzymes is less than many newer drugs. Tranylcypromine only inhibits CYP 450 2A6 (selectively and potently). Phenelzine has no reported interactions, but, like isoniazid, weakly and irreversibly inhibits CYP 450 2C19 and 3A4 in vitro. It might possibly be implicated in interactions (as isoniazid is). Phenelzine has some clinically relevant inhibitory effects on amine oxidases, aminotransferases, and decarboxylases, and it lowers pyridoxal phosphate levels. It commonly causes pyridoxal deficiency, weight gain, sedation, and sexual dysfunction, but only rarely causes hepatic damage and failure, or neurotoxicity. The adverse effects and difficulties with monoamine oxidase inhibitors are less than previously believed or estimated, including a lower risk of hypertension, because the tyramine content in foods is now lower. Potent norepinephrine reuptake inhibitors have a strong protective effect against tyramine-induced hypertension. The newly discovered trace amine-associated receptors probably mediate the pressor response. The therapeutic potential of tranylcypromine and L-dopa in depression and Parkinson disease is worthy of reassessment. Monoamine oxidase inhibitors are not used to an extent proportionate with their benefits; medical texts and doctors' knowledge require a major update to reflect the evidence of recent advances.