The inhibition of monoamine oxidase by tricyclic antidepressants: the influence of the nature of the substrate and the source of the enzyme.

Five tricyclic antidepressants, amitriptyline, clomipramine, desipramine, imipramine and iprindole, have comparable potencies as inhibitors of monoamine oxidase in rodent brain and liver. With rodent brain, potency was always greater with phenethylamine as substrate than with benzylamine, and was generally least with 5-HT. With mouse liver, in which monoamine oxidase is mainly B type, potency with tyramine and dopamine as substrates was close to that found with phenethylamine. The kinetics of inhibition varied with both the substrate and the tissue, and were inconsistent with a simple ping-pong model for substrate oxidation. The relevance of these observations to clinical effectiveness is discussed.