MONOAMINE OXIDASE INHIBITORS. ADVERSE REACTIONS AND POSSIBLE MECHANISMS.

CLINICAL USE of monoamine oxidase (MAO) inhibitors has been characterized by recurrent cycles of enthusiastic reports of therapeutic successes, the occurrence of serious adverse reactions and consequent withdrawal of the original inhibitor, and the synthesis of new compounds. The first cycle began in 1957 when iproniazid (Marsilid), introduced initially for the treatment of tuberculosis, was found to have pronounced euphoric effects that led to its use in the treatment of psychological depression. Since Zeller et al1had already reported that iproniazid was a potent MAO inhibitor, considerable efforts were directed toward relating the beneficial effects of iproniazid to the inhibition of MAO, and many new uses of the compound were suggested. The first cycle was completed in 1960 when iproniazid was removed from the market because of instances of severe and frequently fatal hepatitis. Meanwhile, several new MAO inhibitors had been introduced; some of these were specifically synthesized in