LK 204-545, a highly selective beta1-adrenoceptor antagonist at human beta-adrenoceptors

Eur J Pharmacol. 1999 Feb 19;367(2-3):431-5. doi: 10.1016/s0014-2999(99)00019-9.

Abstract

LK 204-545 ((+/-)-1-(2-(3-(2-cyano-4-(2-cyclopropyl-methoxy-ethoxy)phenoxy)-2-hydro xy-propyl-amino)-ethyl)-3-(4-hydrxy-phenyl) urea), an antagonist that possesses high beta1-/beta2-selectivity in the rat, and a range of cardio-selective and non-selective beta-adrenoceptor antagonists were examined to compare their radioligand binding affinities for human beta1-, beta2- and beta3-adrenoceptors transfected into CHO cells. LK 204-545 and CGP 20712A displayed the highest beta1-/beta2- (approximately 1800 and approximately 650, respectively) and beta1-/beta3-selectivity (approximately 17000 and approximately 2200, respectively) at human beta-adrenoceptors with LK 204-545 being approximately 2.75-fold more beta1-/beta2-selective and approximately 8-fold beta1-/beta3-selective than CGP 20712A. The high potency of LK 204-545 at transfected human beta1-adrenoceptors and in functional models of rat beta1-adrenoceptors together with its high selectivity, identify it as a useful ligand for studying beta1-adrenoceptors and suggest that it may be the preferred ligand for human beta-adrenoceptor studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / metabolism
  • Adrenergic beta-Antagonists / metabolism*
  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • CHO Cells
  • Cricetinae
  • Cyclopropanes / pharmacology*
  • Female
  • Humans
  • Imidazoles / metabolism*
  • In Vitro Techniques
  • Ligands
  • Phenoxypropanolamines
  • Protein Binding
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, beta / metabolism*
  • Receptors, Adrenergic, beta-1 / metabolism
  • Receptors, Adrenergic, beta-2 / metabolism
  • Trachea / physiology*
  • Urea / analogs & derivatives*
  • Urea / pharmacology

Substances

  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Cyclopropanes
  • Imidazoles
  • LK 204-545
  • Ligands
  • Phenoxypropanolamines
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta-2
  • Urea
  • CGP 20712A