LK 204-545, a highly selective β1-adrenoceptor antagonist at human β-adrenoceptors

Abstract

LK 204-545 ((±)-1-(2-(3-(2-cyano-4-(2-cyclopropyl-methoxy-ethoxy)phenoxy)-2-hydroxy-propyl-amino)-ethyl)-3-(4-hydroxyphenyl) urea), an antagonist that possesses high β1-/β2-selectivity in the rat, and a range of cardio-selective and non-selective β-adrenoceptor antagonists were examined to compare their radioligand binding affinities for human β1-, β2- and β3-adrenoceptors transfected into CHO cells. LK 204-545 and CGP 20712A displayed the highest β1-/β2- (~1800 and ~650, respectively) and β1-/β3-selectivity (~17 000 and ~2200, respectively) at human β-adrenoceptors with LK 204-545 being ~2.75-fold more β1-/β2-selective and ~8-fold β1-/β3-selective than CGP 20712A. The high potency of LK 204..