Loss of selectivity of so-called selective alpha 1-adrenoceptor agonists after phenoxybenzamine.
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)
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D000068438:Brimonidine Tartrate; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D010643:Phenoxybenzamine / Q000494:pharmacology*; D010656:Phenylephrine / Q000378:metabolism / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D010656:Phenylephrine; D015016:Yohimbine; D000068438:Brimonidine Tartrate; C014282:cirazoline; D011224:Prazosin