beta-Adrenoceptor blocking activities of nipradilol and its optical isomers in pig coronary artery.
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.
Department of Pharmacology, School of Medicine, University of the Ryukyus, Okinawa, Japan. itomine-ryk@umin.ac.jp
T
T
Itomine
T
T
Matsuzaki
M
M
Sakanashi
N
N
Hobara
M
M
Sakanashi
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007536:Isomerism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011412:Propanolamines / Q000737:chemistry / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D013329:Structure-Activity Relationship; D013552:Swine; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C036089:nipradilol; D007545:Isoproterenol