The stereospecificity of LY253352 for α1‐adrenoceptor binding sites in the brain and prostate

Abstract

1 The stereospecificity of the enantiomers of LY253352, a potent and selective α₁-adrenoceptor antagonist, were studied in the human prostate and canine brain using radioligand receptor binding methods. 2 The mean equilibrium dissociation constant (K_D) in the canine brain and human prostatic adenoma was 84.4 pM and 65.4 pM, respectively. 3 The α₁-adrenoceptor density in the canine brain was approximately eight fold greater than in the human prostatic adenoma. 4 The mean K_i values of (−)-LY253352 and (+)-LY253352 in the prostate were 0.19 nM and 5.79 nM, respectively. 5 The mean K_i values of (−)-LY253352 and (+)-LY253352 in the brain were 0.29 nM and 34.7 nM, respectively. 6 This study indicates that the stereochemical specificity of the optical isomers of LY253352 is a manifestation of differential affinities of the enantiomers for α₁-adrenoceptor binding sites. 7 The differential affinities of (+)-LY253352 in the brain and prostate are suggestive of subtle unique properties of adrenoceptor binding sites in these tissues.