Christopoulos A, Mitchelson F
Department of Pharmaceutical Biology and Pharmacology, Victorian College of Pharmacy (Monash University), Parkville, Australia.
Eur J Pharmacol. 1997 Nov 27;339(2-3):153-6. doi: 10.1016/s0014-2999(97)01379-4.
The mode of interaction of the muscarinic M2 receptor partial agonist, McN-A-343 (4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium), was investigated in the electrically-driven guinea-pig left atrium. Comparison of the negative inotropic responses to this agent with those of the full agonist, carbachol, followed by operational model-fitting, yielded estimates of the dissociation constant (KA) and efficacy (tau) of McN-A-343. Following partial receptor inactivation with propylbenzylcholine mustard, the properties of McN-A-343 as an inhibitor of the carbachol-mediated responses were assessed. Analysis of the data, according to both competitive and allosteric models of interaction, favored the former model. The log KB of McN-A-343 as an antagonist was - 4.65+/-0.06, and was not significantly different from the log KA of this agent as an agonist.
在电驱动的豚鼠左心房中研究了毒蕈碱M2受体部分激动剂McN-A-343（4-（间氯苯基氨甲酰氧基）-2-丁炔基三甲基铵）的相互作用模式。将该药物的负性肌力反应与完全激动剂卡巴胆碱的反应进行比较，然后进行操作模型拟合，得出了McN-A-343的解离常数（KA）和效能（tau）的估计值。在用丙基苄基胆碱芥子气使部分受体失活后，评估了McN-A-343作为卡巴胆碱介导反应抑制剂的特性。根据竞争性和变构相互作用模型对数据进行分析，结果支持前一种模型。McN-A-343作为拮抗剂的log KB为-4.65±0.06，与该药物作为激动剂的log KA无显著差异。
