Functional characterisation of the pharmacological profile of the putative alpha1B-adrenoceptor antagonist, (+)-cyclazosin

Eur J Pharmacol. 1998 Nov 13;361(1):79-83. doi: 10.1016/s0014-2999(98)00735-3.

Abstract

We studied the functional pharmacological profile of (+)-cyclazosin, which has been characterised as a selective, high-affinity (pKi = 9.68) alpha1B-adrenoceptor ligand in binding experiments with rat liver membranes. The pKa/pA2 values for antagonism of contractions mediated via alpha1A/L-adrenoceptors of rat small mesenteric artery, alpha1B-adrenoceptors of rat aorta and alpha1B-adrenoceptors of rat spleen were 7.78 +/- 0.04, 6.86 +/- 0.07 and 7.96 +/- 0.08, respectively. Furthermore, in mouse spleen, which is also regarded as an alpha1B-adrenoceptor preparation, (+)-cyclazosin displayed low potency and did not act as a competitive antagonist. Thus, in contrast with results obtained in radioligand binding experiments, (+)-cyclazosin does not behave as a selective alpha1B-adrenoceptor antagonist in functional tissues. Whether this discrepancy has consequences for the classification of alpha1-adrenoceptors requires further investigation.

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology*
  • Animals
  • Aorta / drug effects
  • Aorta / physiology
  • Dose-Response Relationship, Drug
  • In Vitro Techniques
  • Isometric Contraction / drug effects
  • Male
  • Mesenteric Arteries / drug effects
  • Mesenteric Arteries / physiology
  • Mice
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology
  • Norepinephrine / pharmacology
  • Phenylephrine / pharmacology
  • Quinazolines / pharmacology*
  • Quinoxalines / pharmacology*
  • Rats
  • Rats, Wistar
  • Spleen / drug effects
  • Spleen / physiology
  • Vasoconstrictor Agents / pharmacology

Substances

  • Adrenergic alpha-Antagonists
  • Quinazolines
  • Quinoxalines
  • Vasoconstrictor Agents
  • cyclazosin
  • Phenylephrine
  • Norepinephrine