Venter D P
Department of Pharmacology, Potchefstroom University for Christian Higher Education, South Africa.
Eur J Pharmacol. 1997 Feb 12;320(2-3):233-40. doi: 10.1016/s0014-2999(96)00900-4.
A new method for estimation of agonist-affinity (KA) and relative efficacy was introduced. This method afforded a procedure by which relative efficacy may be estimated while the actual KA values of agonist-receptor complexes are unknown. The relative efficacy may be estimated by employing a newly defined drug parameter, namely the eES value. The eES value is related to drug efficacy and is defined in such a manner that an isolated eES is a meaningful quantity which may indicate whether or not spare receptors are present in an agonist-effector system. The estimation of eES was based on the fact that fixed agonist-competitive antagonist combinations mimic partial agonists and mediate submaximal concentration-effect curves. However, for the practical estimation of eES one may employ data acquired from agonistic concentration-effect curves determined in the absence and presence of increasing concentrations of a competitive antagonist. This procedure was illustrated by utilizing theoretical concentration-effect curves and applied practically by estimating eES and KA values acquired from sets of carbachol and salbutamol curves. The sets of carbachol and salbutamol concentration-effect curves were determined in the absence and presence of their respective competitive antagonists, namely tripitramine and pindolol.
介绍了一种估计激动剂亲和力（KA）和相对效能的新方法。该方法提供了一种在激动剂 - 受体复合物的实际KA值未知时估计相对效能的程序。相对效能可以通过使用新定义的药物参数，即eES值来估计。eES值与药物效能相关，其定义方式使得孤立的eES是一个有意义的量，它可以表明激动剂 - 效应器系统中是否存在备用受体。eES的估计基于这样一个事实，即固定的激动剂 - 竞争性拮抗剂组合模拟部分激动剂并介导次最大浓度 - 效应曲线。然而，对于eES的实际估计，可以使用从在不存在和存在递增浓度的竞争性拮抗剂的情况下测定的激动剂浓度 - 效应曲线获得的数据。通过利用理论浓度 - 效应曲线说明了该程序，并通过估计从卡巴胆碱和沙丁胺醇曲线组获得的eES和KA值进行了实际应用。卡巴胆碱和沙丁胺醇浓度 - 效应曲线组是在不存在和存在它们各自的竞争性拮抗剂，即曲匹拉明和平吲哚洛尔的情况下测定的。
