beta-Adrenoceptor blocking activities of nipradilol and its optical isomers in pig coronary artery.

摘要

1. beta-Adrenoceptor blocking activities of nipradilol, its four optical isomers (RR, RS, SR, SS) and denitro nipradilol were evaluated using pig isolated coronary arteries. 2. (-)-Isoprenaline produced concentration-dependent relaxations of the arteries, which were antagonized by nipradilol, its four optical isomers or denitro nipradilol under KCl-induced contracture. 3. The order of pA2 values for beta-adrenoceptor blocking activities was SR > nipradilol > SS > or = denitro nipradilol > RR > RS. 4. The nitroxy group in nipradilol appears to enhance its beta-adrenoceptor blocking activity, because the beta-adrenoceptor blocking activity of nipradilol was more potent than that of denitro nipradilol. 5. Isomers that have the S configuration (SR, SS) at the 2' position (having a hydroxyl group) in the aryloxypropanolamine showed more potent beta-adrenoceptor blocking activity than isomers that have the R configuration (RR, RS). 6. Isomers that have the R configuration (SR, RR) at the 3 position (having a nitroxy group) in the benzopyran ring showed more potent beta-adrenoceptor blocking activity than those with the S configuration (SS, RS). 7. It is suggested that the difference in configuration of the chemical structure of nipradilol may result in variations of binding affinity for the beta-adrenoceptor.