Loss of selectivity of so-called selective alpha 1-adrenoceptor agonists after phenoxybenzamine

Abstract

This study examined the nature of alpha-adrenoceptor subtype involved in pressor responses to so-called selective alpha 1-adrenoceptor agonists after treatment with phenoxybenzamine in vivo. The influence of prazosin (0.1 mg/kg) and of yohimbine (1 mg/kg) on the dose-response curves for cirazoline in the pithed rat, and for phenylephrine in the anaesthetized dog were compared, after various doses of phenoxybenzamine. In the pithed rat, after 0.05 mg/kg phenoxybenzamine, prazosin caused a displacement of the dose-response curve of cirazoline to the right which was much larger than that caused by yohimbine; after 0.3 mg/kg phenoxybenzamine, prazosin and yohimbine caused about equal displacements; after 1 mg/kg phenoxybenzamine, yohimbine caused a marked displacement, while prazosin was without effect. In the anaesthetized dog, after 1 mg/kg phenoxybenzamine, prazosin and yohimbine produced about equal rightward shifts of the dose-response curve for phenylephrine. However, after 3 mg/kg phenoxybenzamine the rightward shift of the dose-response curve for phenylephrine was much larger after yohimbine than after prazosin. In the anaesthetized dog, verapamil (1 mg/kg) caused a small and parallel rightward shift of the dose-response curve for phenylephrine before phenoxybenzmine and a large and nonparallel one after phenoxybenzamine (3 mg/kg); the effect of verapamil on responses to the selective alpha 2-adrenoceptor agonist UK-14,304 (before and after phenoxybenzamine) were similar to those on responses to phenylephrine after phenoxybenzamine.(ABSTRACT TRUNCATED AT 250 WORDS)