Central sympathoinhibitory action of a new type of alpha-1 adrenoceptor antagonist, YM-617, in rats

M Yoshioka, H Togashi, M Abe, T Ikeda, M Matsumoto and H Saito

First Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.

The structurally new type of alpha-1 adrenoceptor antagonist, YM-617 [R- (-)-5-[2-[(2-(o-ethoxyphenoxy)ethyl]amino)propyl]-2- methoxybenzenesulfonamide hydrochloride], is a phenethylamine derivative which is similar structurally to the catecholamines. The present study was undertaken to elucidate the effect of YM-617 on sympathetic nerve activity and baroreceptor afferent nerve activity in anesthetized rats. Intravenous administration of YM-617 (2, 10 and 50 micrograms/kg) produced a dose-dependent reduction in mean arterial pressure accompanied with bradycardia. YM-617 caused dose-dependent decreases in renal sympathetic nerve activity along with this hypotension. Cardiac sympathetic nerve activity, preganglionic adrenal nerve activity as well as aortic depressor nerve activity was decreased by YM-617. When an equihypotensive dose of YM-617 and a centrally acting antihypertensive drug, clonidine, were compared, the sympathoinhibitory potency of YM-617 was less than that of clonidine. These findings suggest that YM-617 might possess a central sympathoinhibitory action which could play a role in its antitachycardic or bradycardic effect and could be partially responsible for its hypotensive action.

Volume 253, Issue 2, pp. 427-431, 05/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics