Bupropion hydrochloride ((±) α‐t‐butylamino‐3‐chloropropiophenone HCl): a novel antidepressant agent

Tricyclic compounds such as amitriptyline and related substances are considered to be clinically effective antidepressant agents (Kuhn, 1958; Hollister, 1972) with a mode of action dependent on the inhibition of the neuronal reuptake of one or more biogenic amine transmitters in the central nervous system (Glowinski & Axelrod, 1964). The tricyclics have not proved to be ideal agents in treating depression due to their slow OllSet of action, cholinolytic side effects, interactions with pressor amines and monoamine oxidase inhibitors and also due to a tendency to elicit cardiac arrhythmias Or standstill (Jefferson, 1975). Monoamine oxidase inhibitors are likewise considered to be effective antidepressant agents (American Psychiatric Association, 1974) which act by inhibiting intraneuronal monoamine Omdase in the central nervous system (cns). However, the currently available inhibitors also inhibit monow e oxidase in the liver and the ingestion of phenethylamine-type pressor substances in the diet, ‘WY an event made innocuous with the effective of the amines by liver monoamine oxidase, Correspondence. may lead to hypertensive crisis (Marley & Blackwell, 1970). We therefore sought an agent that would be active in antidepressant screening models, but differ chemically and pharmacologically from the tricyclics, and not be sympathomimetic, cholinolytic nor an inhibitor of monoamine oxidase. Bupropion (Wellbatrin) which was synthesized by one of the authors (N.B.M.) (Baltzly & Mehta, 1968; Mehta, 1974, 1975) meets these criteria and has the following structure: