卡替洛尔（一种在豚鼠盲肠带具有内在拟交感神经活性的β-肾上腺素受体阻滞剂）的β-肾上腺素能拟似作用和β-肾上腺素能阻断作用中的立体选择性。

Stereoselectivity in beta-adrenomimetic and beta-adrenolytic actions of carteolol, a beta-adrenoceptor blocker with intrinsic sympathomimetic action in guinea-pig taenia caecum.

Takayanagi I, Hagiwara H, Koike K

Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.

Gen Pharmacol. 1990;21(3):309-12. doi: 10.1016/0306-3623(90)90828-a.

Abstract

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.

摘要

在豚鼠盲肠带中测试了β-肾上腺素能部分激动剂（具有内在拟交感神经活性的β-肾上腺素受体阻滞剂）卡替洛尔的S(-)和R(+)异构体的β-肾上腺素能激动和β-肾上腺素能拮抗活性。2. 卡替洛尔的S(-)和R(+)异构体的β-肾上腺素受体阻断活性（pA2值）显著大于相应的β-肾上腺素能激动活性（pD2值），这支持了我们的观点，即β-肾上腺素受体包含两个不同的结合位点：高亲和力位点和低亲和力位点。3. 在β-肾上腺素受体阻断作用中，S(-)卡替洛尔的效力约为R(+)卡替洛尔的10倍，而S(-)卡替洛尔的β-肾上腺素能激动作用约为R(+)卡替洛尔的2倍。此外，S(-)卡替洛尔的内在活性略高于但显著高于R(+)卡替洛尔。4. 这些结果表明，S(-)异丙肾上腺素与S(-)、R(+)和RS(+/-)卡替洛尔之间竞争性拮抗的结合位点比诱导β-肾上腺素能激动作用的结合位点更具立体选择性。