Interactions between relatively selective monoamine oxidase inhibitors and an inhibitor of 5-hydroxytryptamine re-uptake, clomipramine.

Features of interactions with combined antidepressants in man were evoked by clomipramine in rats pretreated with both the relatively selective monoamine oxidase (MAO) inhibitors clorgyline and deprenyl, but not when clomipramine was given to rats pretreated with deprenyl or clorgyline alone, i.e. inhibition of both MAO A and B was a likely prerequisite for clomipramine to elicit the syndrome (with the larger dose of clorgyline and deprenyl, MAO A and B inhibition exceeded 95%). The features evoked were myoclonic--forelimb flexor-extensor movements, wet dog shakes and head and body twitches; hyperthermia and ECG anomalies also developed, and locomotor activity was augmented. Myoclonic phenomena were prevented when the above pretreatment also included p-chlorophenyl-alanine, but were unaffected or even intensified when pretreatment instead included alpha-methyl-p-tyrosine; these phenomena were attenuated or abolished by pirenperone, a 5HT2 antagonist. Relevance of these findings to safer combinations of antidepressants is discussed.