Iproniazid (Marsilid, Rivivol, Euphozid, Iprazid, Ipronid, Ipronin) is a non-selective, irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class.

[1] It was withdrawn in most of the world a few years later in 1961 due to a high incidence of hepatitis, and was replaced by less hepatotoxic drugs such as phenelzine and isocarboxazid.

[1] Canada surprisingly withdrew iproniazid in July 1964 due to interactions with food products containing tyramine.

[6][7] Nevertheless, iproniazid has historic value as it helped establish the relationship between psychiatric disorders and the metabolism of neurotransmitters.

Subsequently, the C=N linkage is selectively hydrogenated in the presence of a platinum catalyst and with water, alcohol or acetic acid as solvent.

In the presence of oxygen it is an irreversible reaction, as dehydrogenation of iproniazid at the active site of the enzyme takes place.

[18] Inhibition of MAOs by iproniazid is competitive and sensitive to changes in pH and temperature, similar to oxidation of the monoamine substrate.

[19] The presence of the isopropyl radical was indicated by another observed product of the metabolism of iproniazid: the gas propane.

[3] The isopropyl radical formed as a result of the metabolism of iproniazid, is able to covalently bind to proteins and other macromolecules in the liver.

Covalent binding results in liver necrosis by presumably changing protein function leading to organelle stress and acute toxicity.

An inducer of a class of hepatic microsomal cytochrome P450 enzymes, phenobarbital, highly increased the chance of necrosis.

In contrast, the compounds cobalt chloride, piperonyl butoxide and alpha-naphthylisothiocyanate inhibit microsomal enzymes which resulted in a decreased chance of necrosis due to isopropyl hydrazine.

[3] Isonicotinic acid, formed during the hydrolysis of iproniazid, is described as a moderately toxic compound and allergen with cumulative effects.

[6][7] Excretion can occur via different routes: via the lungs, the urine, bile and sometimes via the skin or breast milk.

Moreover, usage of iproniazid results in several adverse effects such as dizziness (when lying down), drowsiness, headaches, ataxia, numbness of the feet and hands, and muscular twitching.

[26][27] Rat animal models have been used to investigate the hepatotoxic (bio)chemical mechanism of iproniazid.