Effect of Imipramine, Amitriptyline and Their Monomethyl Derivatives on Reserpine Activity

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Abstract
Impramine, amitriptyline and their respective N-monomethyl derivatives (desmethylimipramine and desmethylamitriptyline) prevent reserpine activity to varying degrees. Desmethylimipramine and desmethylamitriptyline are more effective than are imipramine and amitriptyline in reducing the hypothermia induced by reserpine in rats. Imipramine and desmethylimipramine are more effective than are amitriptyline and desmethylamitriptyline in decreasing the severity of gastric ulcers induced by reserpine in restrained rats. Desmethylimipramine does not prevent the lowering of brain amines by reserpine. The antagonistic effect of imipramine toward leptazol convulsions in mice is not shared by desmethylimipramine. Imipramine and desmethylimpramine do not potentiate the central effects of 5-hydroxy- tryptophan and tryptamine and do not prevent the hypothermia induced by 5-hydroxytryptamine, α-methyl-dopa or chlorpromazine. The activity of desmethylimipramine may be differentiated therefore on a pharmacological basis from that of the monoamine oxidase inhibitors and amphetamine.