Nipradilol Displays a Unique Pharmacological Profile of Affinities for the Different α1-Adrenoceptor Subtypes

[摘要] References(31)Cited-By(1)The selectivity of antagonistic effects of nipradilol, its four isomers and denitronipradilol, a major metabolite of nipradilol, on α1-adrenoceptor subtypes in rat heart, brain and spleen were examined by radioligand binding assay with [3H]-prazosin. Pharmacological characteristics of these compounds were determined in isolated aortae from rats and guinea pigs. The order of the pKi values for α1High-affinity sites in the heart, spleen and brain was SR 〉> nipradilol ≥ RR ≥ SS ≈ RS » denitronipradilol, but the order of the pKi values for the α1LOW -affinity sites was different in the heart and brain. There were good correlations between the pKi values of these compounds for the α1High -affinity sites and the pA2 values for the contractile inhibition of the phenylephrine-induced response in rat aorta. There was no correlation between the pKi values of these compounds for the α1LOW -affinity sites and the pA2 values. These results indicate that: 1) α1High -Affinity sites are related to vasoconstriction mediated by α1- adrenoceptors; 2)Nipradilol and its isomers possess low affinity to α1 -adrenoceptors; and 3)The nitroxy group in nipradilol is important for its α1-blocking activity.

[学科分类] 药理学

[关键词] [3H]-Prazosin;Nipradilol;α1-Adrenoceptor subtype;α1- and β- Blocking activity;Optical isomer