Central sympathoinhibitory action of a new type of alpha-1 adrenoceptor antagonist, YM-617, in rats.
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.
First Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
M
M
Yoshioka
H
H
Togashi
M
M
Abe
T
T
Ikeda
M
M
Matsumoto
H
H
Saito
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D004594:Electrophysiology; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D012313:RNA / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D000096926:Benzenesulfonamides
D000317:Adrenergic alpha-Antagonists; D003000:Clonidine; D012313:RNA; D013449:Sulfonamides; C044648:YM 12617; D000096926:Benzenesulfonamides