Enthalpy‐entropy relationship in drug‐cholinoceptor interaction: a new approach

Open Access
Publisher Website
Google Scholar
Abstract
1 The partial molal volume at infinite dilution, , was determined in toluene, benzene and acetonitrile for fifteen different drug molecules comprising muscarinic agonists, partial agonists and antagonists. 2 The difference in between a given drug, X, and hyoscine, expressed as was then multiplied by the internal pressure of the holding phase (P1 ∼ cohesive energy density) in order to obtain an estimate of the excess enthalpy (ΔH) over hyoscine in the interaction of drug molecule X with a common cholinoceptor. As a working hypothesis, ΔH for hyoscine is taken as zero, hyoscine having the lowest /affinity ratio of any drug in the series investigated. 3 The corresponding change in entropy (ΔS) was then calculated from the relationship: RT ln Kx= Pi, where Kx is the affinity constant of drug molecule X to the common cholinoceptor, obtained independently. 4 Linear regression of P1 ⋍ ΔH from the data in acetonitrile over ΔS gave a satisfactory isoequilibrium plot, r2 = 0.954, slope (β) = 231°K. 5 The present approach offers a new course for the study of the enthalpy-entropy relationship in the interaction of drug molecules in a given series with a common receptor. It could provide an alternative to the Van't Hoff procedure for the estimation of relative ΔH, and is independent of the free energy of binding (ΔG).