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

Naunyn Schmiedebergs Arch Pharmacol. 1988 Sep;338(3):234-8. doi: 10.1007/BF00173393.

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)

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology*
  • Animals
  • Blood Pressure / drug effects*
  • Brimonidine Tartrate
  • Dogs
  • Dose-Response Relationship, Drug
  • Female
  • Imidazoles / pharmacology
  • Male
  • Phenoxybenzamine / pharmacology*
  • Phenylephrine / metabolism
  • Phenylephrine / pharmacology
  • Prazosin / pharmacology
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic, alpha / metabolism*
  • Yohimbine / pharmacology

Substances

  • Adrenergic alpha-Agonists
  • Imidazoles
  • Quinoxalines
  • Receptors, Adrenergic, alpha
  • Phenoxybenzamine
  • Phenylephrine
  • Yohimbine
  • Brimonidine Tartrate
  • cirazoline
  • Prazosin