抗组胺H1拮抗剂特非那定及一些相关化合物的钙拮抗作用与结构-亲和力关系

Calcium antagonism and structure-affinity relationships of terfenadine, a histamine H1 antagonist, and some related compounds.

作者信息

Zhang M Q, Caldirola P, Timmerman H

机构信息

Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, Amsterdam, The Netherlands.

出版信息

J Pharm Pharmacol. 1993 Jan;45(1):63-6. doi: 10.1111/j.2042-7158.1993.tb03681.x.

DOI:10.1111/j.2042-7158.1993.tb03681.x

PMID:8094450

Abstract

Calcium channel affinity of terfenadine and its optical isomers was determined by the displacement of [3H]nitrendipine on rat cerebral cortex membranes. Terfenadine showed a pKd of 6.36 +/- 0.03 whereas its R(+)-isomer (VUF4567) had a pKd value of 6.39 +/- 0.03 and the S(-)-isomer (VUF4568) had a pKd of 6.40 +/- 0.04. The same affinity between the enantiomers suggests that the binding domain on the membrane is not sterically restricted towards the part of the molecule in which the chiral centre is present. The characteristics of terfenadine in regulating [3H]nitrendipine binding were similar to those of some other diphenyl-alkylamine type calcium antagonists. It allosterically altered the binding affinity for nitrendipine and acted at the same site linked to the calcium channel as gallopamil. A structure-affinity relationship among a group of terfenadine analogues is discussed.

摘要

通过[3H]尼群地平在大鼠大脑皮层膜上的置换作用，测定了特非那定及其光学异构体对钙通道的亲和力。特非那定的解离常数（pKd）为6.36±0.03，而其R(+)-异构体（VUF4567）的pKd值为6.39±0.03，S(-)-异构体（VUF4568）的pKd为6.40±0.04。对映体之间相同的亲和力表明，膜上的结合结构域对手性中心所在分子部分的空间位阻不受限。特非那定调节[3H]尼群地平结合的特性与其他一些二苯基烷基胺类钙拮抗剂相似。它变构改变了对尼群地平的结合亲和力，并且与加洛帕米作用于与钙通道相连的同一部位。文中讨论了一组特非那定类似物的构效关系。