Elsevier

Life Sciences

Volume 29, Issue 4, 27 July 1981, Pages 313-330
Life Sciences

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Quantitative analysis of drug-receptor interactions: I. Determination of kinetic and equilibrium properties

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Abstract

It has recently become possible to characterize a variety of different receptors by studying the binding of appropriate drugs labelled with 3H or 125I. 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.

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