β-肾上腺素能部分激动剂贝凡洛尔和卡替洛尔的R(+)-和S(-)-异构体与豚鼠睫状体、右心房和气管微粒体部分β-肾上腺素能受体高亲和力位点相互作用的比较。

Comparison of interactions of R(+)- and S(-)-isomers of beta-adrenergic partial agonists, befunolol and carteolol, with high affinity site of beta-adrenoceptors in the microsomal fractions from guinea-pig ciliary body, right atria and trachea.

Koike K, Horinouchi T, Takayanagi I

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

Gen Pharmacol. 1994 Nov;25(7):1477-81. doi: 10.1016/0306-3623(94)90177-5.

Abstract

The stereoselectivities of beta-adrenergic partial agonists for the high affinity binding site of beta-adrenoceptors in the guinea-pig ciliary body, right atria and trachea were studied. 2. The inhibition curves by the S(-)-isomers of befunolol and carteolol were not significantly different from that by the R(+)-isomers in the guinea-pig ciliary body. 3. The inhibition curves by the S(-)-isomers of befunolol and carteolol were about 10 times as potent as the R(+)-isomers in the guinea-pig atria and trachea. 4. The pKi values of the S(-)-isomers of befunolol and carteolol were significantly larger than those of R(+)-isomers in the guinea-pig atria and trachea but not larger than those of the R(+)-isomers in the guinea-pig ciliary body. 5. These results suggest that the high affinity binding site of beta-adrenoceptors in ciliary body cannot discriminate stereoselectively between the R(+)- and S(-)-isomers, while in other tissues there is stereoselectivity between the two enantiomers.

摘要

研究了β-肾上腺素能部分激动剂对豚鼠睫状体、右心房和气管中β-肾上腺素能受体高亲和力结合位点的立体选择性。2. 在豚鼠睫状体中，贝凡洛尔和卡替洛尔的S(-)-异构体的抑制曲线与R(+)-异构体的抑制曲线无显著差异。3. 在豚鼠心房和气管中，贝凡洛尔和卡替洛尔的S(-)-异构体的抑制曲线效力约为R(+)-异构体的10倍。4. 在豚鼠心房和气管中，贝凡洛尔和卡替洛尔的S(-)-异构体的pKi值显著大于R(+)-异构体的pKi值，但在豚鼠睫状体中不大于R(+)-异构体的pKi值。5. 这些结果表明，睫状体中β-肾上腺素能受体的高亲和力结合位点不能对R(+)-和S(-)-异构体进行立体选择性区分，而在其他组织中，这两种对映体之间存在立体选择性。