Effect of SM-2470, a newly synthetized alpha 1-adrenoceptor antagonist, on sympathetic nerve activity in anesthetized...

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.