Nariman Bomanshaw Mehta

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:

Pharmacological Properties of 403U76, a New Chemical Class of 5-Hydroxytryptamine- and Noradrenaline-reuptake Inhibitor

403U76 (5‐chloro‐[[2‐[(dimethylamino)methyl]phenyl]thio]benzene‐methanol hydrochloride) is a potent, competitive, inhibitor of 5‐hydroxytryptamine (5‐HT) and noradenaline reuptake into rat brain synaptosomes. Inhibition of 5‐HT uptake in‐vivo by 403U76 was demonstrated by potentiation of the behavioural effects of 5‐hydroxytryptophan in rats and mice and blockade of p‐induced depletion of 5‐HT in rats.

Synthesis and evaluation of the anticonvulsant activity of a series of 2-amino-1-phenyl-1-propanols derived from the metabolites of the antidepressant bupropion

Abstract A series of 2-amino-1-phenyl-1-propanols that are structurally related to known metabolites of bupropion,1 (Wellbutrin®) were synthesized and evaluated as potential anticonvulsants. The ( R ∗ ,R ∗ )-2-tert- butylamino -1-(3- trifluoromethylphenyl ) propanol 20 had an ED50 of 16.5 ± 2.8 mg/kg ip in mice in the maximal electroshock screen and was chosen for further evaluation.

Synthesis and anticonvulsant activity of a series of benzamides

Summary A series of benzamides containing N,N,2-trimethyl-1,2-propane diamine as the amide moiety was synthesized. The compounds were evaluated in the maximal electroshock (MES) and pentylenetetrazol (metrazole, MET) screens for anticonvulsant activity. The 3,5-trifluoromethyl, 3,5-dichloro, and 3-bromo analogues proved to be either equipotent with or more potent than phenytoin.

Separations of Threo-Erythro Aminoalcohols by Preparative HPLC

Abstract A liquid chromatographic method which enables the separation of the threo/erythro diastereoisomers obtained from the reduction of WellbutrinTM brand bupropion using a ternary eluent system is described. This has been achieved on a preparative scale.