Steric aspects of adrenergic drugs. II. Effects of DL isomers and desoxy derivatives on the reserpine-pretreated vas deferens.

Abstract

The Easson-Stedman hypothesis that dextro isomers of sympathomimetic amines have pharmacologic activities similar to their corresponding desoxy derivatives was tested in the catecholamine-depleted (reserpine, 5 mg/kg i.p., 16-24 hr previously) rat vas deferens. Cumulative dose-response curves were obtained, in vitro, for D and L isomers of norepinephrine, epinephrine, cobefrin, metaraminol, phenylephrine, synephrine, octopamine, norephedrine and ephedrine and their corresponding desoxy derivatives, dopamine, epinine, α-methyldopamine, α-methyl- m -tyramine, m -tyramine, N-methyltyramine, tyramine, (+)-amphetamine and (+)-methamphetamine, respectively. All D(-) isomers retained their ability to produce a contraction and were more active than their L(+) isomers or desoxy derivatives. L(+)-Norepinephrine and L(+)- epinephrine are essentially directly-acting and their effects were equal to those of dopamine and epinine, respectively. All other L(+) isomers possess a considerable indirect component, as do their desoxy derivatives, and both groups produced essentially similar effects. The results suggest that the Easson-Stedman hypothesis holds true over a wide range of substances in the catecholamine-depleted preparation but not in the untreated preparation where the dose-response curves of indirectly-acting desoxy derivatives and L(+) isomers appear to be related to their known affinity for catecholamine uptake sites. Further classification of sympathomimetic amines is carried out.