The newly synthetized alpha 1-adrenoceptor antagonist,
SM-2470 (4-amino-2-[4-(bicyclo(2,2,2)oct-2-ene-5-carbonyl)-1-piperazinyl]-6,7- dimethoxyquinazoline hydrochloride), is a
prazosin-like
quinazoline derivative. The present study was undertaken to elucidate the effect of
SM-2470 on sympathetic nerve activity and baroreceptor afferent nerve activity in anesthetized rats.
Intravenous administration of
SM-2470 (10, 30 and 100 micrograms/kg) produced a dose-dependent reduction of mean arterial pressure without any significant change in heart rate.
SM-2470 caused decreases in both renal and cardiac sympathetic nerve activity along with this
hypotension. Preganglionic adrenal nerve activity and aortic depressor nerve activity were also decreased by
SM-2470. When equi-hypotensive doses of
SM-2470 and
clonidine were compared, the sympathoinhibitory potency of
SM-2470 was less than that of the centrally acting
antihypertensive drug,
clonidine. Pretreatment with
SM-2470 (30 micrograms/kg, i.v.) shifted the
methoxamine-induced pressor response curve to the right. These findings suggest that
SM-2470 may possess a central sympathoinhibitory action. This central action may play a role in its anti-tachycardic effect and may be substantially responsible for the hypotensive action.