(+)-Cyclazosin, a selective alpha1B-adrenoceptor antagonist: functional evaluation in rat and rabbit tissues

Eur J Pharmacol. 2005 Oct 17;522(1-3):100-7. doi: 10.1016/j.ejphar.2005.08.044. Epub 2005 Oct 6.

Abstract

To shed light on the discrepancy between reported binding and functional affinity and selectivity at alpha(1b/B)-adrenoceptors, the antagonist (+)-cyclazosin was reinvestigated in rat and rabbit tissues. It displayed a competitive antagonism at alpha(1A) and alpha(1D)-adrenoceptors of rat prostatic vas deferens and aorta with pA(2) values 7.75 and 7.27, respectively. In rabbit thoracic aorta (+)-cyclazosin competitively antagonized noradrenaline-induced contractions at alpha(1B)-adrenoceptors with a pA(2) value of 8.85, whereas its affinity at alpha(1L)-adrenoceptors was markedly lower (pA(2) = 6.75-7.09). In conclusion, these data confirmed that (+)-cyclazosin is a selective alpha(1B)-adrenoceptor antagonist also in functional assays, showing 13- and 38-fold selectivity for the alpha(1B)-adrenoceptor over alpha(1A)- and alpha(1D)-subtypes, respectively. Furthermore, (+)-cyclazosin displayed a significant selectivity for alpha(1B)-adrenoceptors relative to the alpha(1L)-subtype.

Publication types

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

MeSH terms

  • Adrenergic alpha-1 Receptor Agonists
  • Adrenergic alpha-1 Receptor Antagonists*
  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic alpha-Antagonists / pharmacology*
  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / physiology
  • Binding, Competitive
  • Clonidine / analogs & derivatives
  • Clonidine / pharmacology
  • Dose-Response Relationship, Drug
  • In Vitro Techniques
  • Male
  • Methoxamine / pharmacology
  • Molecular Structure
  • Muscle Contraction / drug effects
  • Norepinephrine / pharmacology
  • Quinazolines / chemistry
  • Quinazolines / pharmacology*
  • Quinoxalines / chemistry
  • Quinoxalines / pharmacology*
  • Rabbits
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, alpha-1 / physiology
  • Vas Deferens / drug effects
  • Vas Deferens / physiology
  • Vasoconstriction / drug effects

Substances

  • Adra1a protein, rat
  • Adra1b protein, rat
  • Adra1d protein, rat
  • Adrenergic alpha-1 Receptor Agonists
  • Adrenergic alpha-1 Receptor Antagonists
  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Quinazolines
  • Quinoxalines
  • Receptors, Adrenergic, alpha-1
  • cyclazosin
  • chlorethylclonidine
  • Methoxamine
  • Clonidine
  • Norepinephrine