海巴辛的变构结合特征：与其他心脏选择性毒蕈碱拮抗剂的比较。

The allosteric binding profile of himbacine: a comparison with other cardioselective muscarinic antagonists.

作者信息

Lee N H, el-Fakahany E E

机构信息

Department of Pharmacology and Toxicology, University of Maryland School of Pharmacy, Baltimore 21201.

出版信息

Eur J Pharmacol. 1990 Apr 10;179(1-2):225-9. doi: 10.1016/0014-2999(90)90424-5.

DOI:10.1016/0014-2999(90)90424-5

PMID:2364985

Abstract

The possibility of an allosteric interaction by himbacine, a cardioselective antagonist, with rat cardiac muscarinic receptors was studied. Himbacine allosterically decelerated the dissociation of bound [3H]N-methylscopolamine [( 3H]NMS) in a concentration-dependent manner with an IC50 value of 103.7 microM. When compared to the IC50 values of other cardioselective antagonists, the rank order of potencies was: methoctramine greater than gallamine greater than himbacine greater than AF-DX 116. In contrast, the potencies of these compounds to displace [3H]NMS binding were: himbacine greater than methoctramine greater than AF-DX 116 greater than gallamine. The allosteric potencies were found not to be correlated with binding potencies (correlation coefficient = -0.15). A striking common feature of the cardioselective antagonists is their ability to bind to an allosteric site on cardiac muscarinic receptors.

摘要

研究了心脏选择性拮抗剂辛巴生（himbacine）与大鼠心脏毒蕈碱受体发生变构相互作用的可能性。辛巴生以浓度依赖性方式变构减缓结合的[³H]N-甲基东莨菪碱（[³H]NMS）的解离，IC50值为103.7微摩尔。与其他心脏选择性拮抗剂的IC50值相比，效价顺序为：甲奥克生（methoctramine）＞加拉明（gallamine）＞辛巴生＞AF-DX 116。相反，这些化合物取代[³H]NMS结合的效价为：辛巴生＞甲奥克生＞AF-DX 116＞加拉明。发现变构效价与结合效价不相关（相关系数 = -0.15）。心脏选择性拮抗剂的一个显著共同特征是它们能够结合到心脏毒蕈碱受体上的变构位点。