Iproniazid Sympathomimetics

The first generation of antidepressants, MAO (monoamine oxidase) inhibitors, inhibited neurotransmitter degradation by inhibiting monoamine deoxidase, a flavin containing enzyme, found in the mitochondria of neurons and other cell types, that oxidatively deaminates naturally occurring sympathomimetic monoamines, such as norepinephrine, dopamine, and serotonin within the presynapse. In 1952, isoniazid and its isopropyl derivative, iproniazid (1), were developed for the treatment of tuberculosis, where it was subsequently found that these agents had a mood enhancing effect on... 

Some drugs are competitive inhibitors of nonmicrosomal metabolic pathways. Serious reactions have been reported in patients treated with an MAO inhibitor, such as trancypromine or iproniazid, because they usually are sensitive to a subsequent dose of a sympathomimetic amine (e.g., amphetamine) or a tricyclic antidepressant (e.g., amitriptyline), which is metabolized by MAO. 

Switching from iproniazid to tranylcypromine/triftuoperazine may have been the cause of a fatal reaction (fever, shivering, sweating, cyanosis) in a patient also given ephedrine (see also MAOIs or RIMAs -i-Sympathomimetics Indirectly-acting , p. 1147). 

Potentiating effect of iproniazid on the pharmacological action of sympathomimetic amines, Proc. Soc, Exp. Biol. Med. 84, 699 (1953). 

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