Further validation of in vivo and in vitro pharmacological procedures for assessing the alpha 2/alpha 1-selectivity of test compounds: (1). Alpha-adrenoceptor antagonists

Eur J Pharmacol. 1986 Sep 23;129(1-2):49-55. doi: 10.1016/0014-2999(86)90335-3.


Twenty one chemically dissimilar alpha-adrenoceptor antagonists were assessed in 7 different tests. The potencies of the compounds to protect rats from norepinephrine lethality were closely correlated with their potencies for inhibition of [3H]WB4101, but not of [3H]clonidine, [3H]idazoxan, [3H]rauwolscine or [3H]yohimbine binding to rat brain homogenates. The reverse was found for the potencies of the compounds to prevent the antidiarrheal effect of clonidine. The in vivo anti-norepinephrine/anti-clonidine potency ratios were highly correlated with the ratios between the in vitro potency to inhibit [3H]WB4101 binding on one hand and [3H]clonidine, [3H]idazoxan, [3H]rauwolscine or [3H]yohimbine binding on the other. The reliability of the above models for measuring alpha 1- and alpha 2-adrenoceptor antagonistic activity and selectivity is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Antagonists / metabolism
  • Adrenergic alpha-Antagonists / pharmacology*
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Clonidine / antagonists & inhibitors
  • Female
  • In Vitro Techniques
  • Male
  • Norepinephrine / antagonists & inhibitors
  • Radioligand Assay
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic, alpha / classification
  • Receptors, Adrenergic, alpha / drug effects*
  • Receptors, Adrenergic, alpha / metabolism


  • Adrenergic alpha-Antagonists
  • Receptors, Adrenergic, alpha
  • Clonidine
  • Norepinephrine