Quantitative analysis of drug-receptor interactions: I. Determination of kinetic and equilibrium properties.
Quantitative analysis of drug-receptor interactions: I. Determination of kinetic and equilibrium properties.
复制标题
药物-受体相互作用的定量分析：I.动力学和平衡特性的测定。
DOI：
10.1016/0024-3205(81)90324-6
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发表时间：
1981
期刊：
影响因子：
6.1
通讯作者：
Molinoff,PB
中科院分区：
文献类型：
--
作者：
Weiland,GA;Molinoff,PB
最近，通过研究3 H或125 I标记的适当药物的结合，可以表征各种不同的受体。这篇综述的目的是描述基本的数学分析，应用于表征一个特定的受体与配体的相互作用。简单的双分子药物-受体相互作用的动力学和平衡常数的直接测定方法被描述为使用这些测量来验证一个简单的二级反应的存在。一些偏离二阶行为，这意味着更复杂的相互作用的原因也进行了讨论。放射性配体结合的体外研究提供了一种间接测定未标记药物的平衡解离常数的方法。这些测定的适当的方程，并确定这些计算所依据的假设。动力学和平衡常数的温度依赖性的分析允许确定的结合的能量和方法的吉布斯自由能，焓和熵的变化，与配体受体的结合计算。激动剂和拮抗剂与β-肾上腺素能受体的相互作用的研究作为各种类型的计算的例子。
It has recently become possible to characterize a variety of different receptors by studying the binding of appropriate drugs labelled with 3 H or 125 I. The goal of this review is to describe the basic mathematical analyses that should be used to characterize a particular receptor in terms of its interactions with ligands. Methods for direct determination of kinetic and equilibrium constants of simple bimolecular drug-receptor interactions are described as is the use of these measurements to verify the existence of a simple second order reaction. Some of the causes of deviations from second order behavior which imply more complex interactions are also discussed. In vitro studies of radioligand binding provide a means of indirectly determining equilibrium dissociation constants of unlabelled drugs. The appropriate equations for these determinations are presented and the assumptions underlying these calculations are identified. Analysis of the temperature dependence of kinetic and equilibrium constants allows determination of the energetics of binding and methods are presented for calculation of the changes in Gibbs free energy, enthalpy and entropy that are associated with the binding of ligands to receptors. Studies of the interactions of agonists and antagonists with β-adrenergic receptors are presented as examples of the various types of calculations.