binding of iproniazid derivatives to liver proteins would induce liver necrosis remains unclear. Cytochrome P450 enzymes are present at the highest concentrations in the liver, causing most alkylating agents to be produced in the liver. This explains why the liver is mostly damaged by covalent binding of alkylating agents such as the isopropyl radical. Rat models and other animal models have shown that cytochrome P450 enzymes convert isopropyl hydrazine to alkylating compounds that induce liver necrosis. 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. Metabolism to other forms Iproniazid can also be metabolised by O-dealkylation from iproniazid to acetone and isoniazid. Isoniazid can undergo further metabolism via multiple metabolic pathways, of which one eventually results in alkylating agents as well. This toxifying metabolic pathway includes N-acetylation. Reactions involving acetylation are influenced by genetic variance: the acetylator phenotype. The toxicological response to isoniazid (and thus iproniazid) can therefore be subjected to interindividual differences. Acetone can also be produced in alternative pathway as a metabolite of isopropyl hydrazine. It is eventually converted to CO2 and exhaled. Isonicotinic acid Isonicotinic acid, formed during the hydrolysis of iproniazid, is described as a moderately toxic compound and allergen with cumulative effects. Isonicotinic acid is further metabolized by glycine-conjugation or glucuronic acid-conjugation. Other toxic effects Iproniazid can also interact with tyrosine-containing food products which may have toxic effects. Excretion Excretion can occur via different routes: via the lungs, the urine, bile and sometimes via the skin or breast milk. Iproniazid has a molecular weight of 179.219 g/mol, which is far below 500 g/mol, and it is hydrophilic (because of e.g. the N-H groups in the molecule). These two properties together indicate that iproniazid is likely to be excreted in the urine via the kidneys. Iproniazid can also be metabolized and excreted afterwards in the form of one of its metabolites which can be found in the figure above. Isoniazid is hydrophilic and has a molecular weight of 137.139 g/mol. Isoniazid is therefore expected to be excreted via the urine, if it is not further metabolized in the body. The same holds for isonicotinic acid and isonicotinoyl glycine. Carbon dioxide and propane are gaseous which are presumably transported out of the body