Stereoselectivity in beta-adrenomimetic and beta-adrenolytic actions of carteolol, a beta-adrenoceptor blocker with intrinsic sympathomimetic action in guinea-pig taenia caecum.
1. The beta-adrenomimetic and beta-adrenolytic activities of S(-) and R(+) isomers of carteolol, a beta-adrenergic partial agonist (a beta-adrenoceptor blocker with intrinsic sympathomimetic action) were tested in the guinea-pig taenia caecum. 2. The beta-adrenoceptor blocking activities (pA2 values) of S(-) and R(+) isomers of carteolol were significantly larger than the corresponding beta-adrenomimetic activities (pD2 values), supporting our views that beta-adrenoceptors contain two different binding sites; high and low affinity sites. 3. In beta-adrenoceptor blocking action S(-) carteolol was about 10 times as potent as R(+) carteolol while beta-adrenomimetic action of S(-) carteolol was about 2 times as potent as that of R(+) carteolol. Further, intrinsic activity for S(-) carteolol was slightly but significantly larger than that for R(+) carteolol. 4. These results suggest that the binding site for competitive antagonism between S(-) isoprenaline and S(-), R(+) and RS(+/-) carteolol is more stereoselective than the binding site to induce beta-adrenomimetic action.
Takayanagi
I
I
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Hagiwara
H
H
Koike
K
K
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000818:Animals; D002354:Carteolol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002432:Cecum / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology*; D013237:Stereoisomerism
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D002354:Carteolol; D007545:Isoproterenol