The monoamine oxidase inhibitors used in the management of depressive disorders consist of a group of older drugs, which tend to be non-selective and irreversible inhibitors of both monoamine oxidase (MAO) A and B, and a second group of compounds that reversibly inhibit only MAO A (RIMAs). There are also MAO inhibitors that are both selective and irreversible (e.g. clorgyline [MAO A], rasagiline [MAO B]) that will not be discussed here as they are now used only experimentally (clorgyline (1)) or as an anti-Parkinson drug (rasagiline (2)).
The older, non-selective, irreversible drugs have very severe and prolonged toxicity in overdose and potentially life-threatening interactions with tyramine in food and many drugs. The newer, selective, reversible drugs have a much more benign profile in overdose, are safe with food, but may still have life-threatening toxicity when combined with serotonergic drugs and deaths have also been recorded. The fatal toxicity index (FTI) of the monoamine oxidase inhibitors as a group (27.03 deaths per million prescriptions) in England, Scotland and Wales between 1985 and 1989 was significantly lower than the mean of all drugs (35.6) although that of tranylcypromine was higher (3).
Some aspects of the chemistry of these drugs are shown in Table 1 and structural diagrams are found here.
Table 1. Chemistry of monoamine oxidase inhibitors
| Compound | MW | SI Conversion | Therapeutic, toxic concentrations* | United States Pharmacopoeia Dictionary of Drug Names |
| Iproniazid | 179.2 | mg/L x 5.58 = micromol/L | 5 mg/L, N/A | 2-(1-methylethyl)hydrazide-4-pyridinecarboxylic acid |
| Isocarboxazid | 231.3 | mg/L x 4.32 = micromol/L | N/A, N/A | 5-methyl-3-isoxazolecarboxylic acid 2-benzylhydrazide |
| Phenelzine | 136.2 | mg/L x 7.34 = micromol/L | 0.02 mg/L, 0.5 mg/L | (2-phenylethyl)-hydrazine |
| Tranylcypromine | 133.2 | mg/L x 7.51 = micromol/L | 0.1 mg/L, 0.3 mg/L | 2-phenyl-, trans-(+-)-cyclopropanamine |
| Befloxatone | 349.3 | mg/L x 2.86 = micromol/L | N/A, N/A |
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IMW 1/2/04 This article has been used (with permission of MediTox Pty Ltd) as the basis of a chapter on monoamine oxidase inhibitor toxicity in the third edition of Medical Toxicology published by Lippincott Williams Wilkins, 2004.