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Enthalpy‐entropy relationship in drug‐cholinoceptor interaction: a new approach
Author(s) -
Cohen Sasson,
Haberman Frank
Publication year - 1985
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1985.tb11088.x
Subject(s) - enthalpy , thermodynamics , chemistry , molecule , entropy (arrow of time) , stereochemistry , organic chemistry , physics
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 ( P 1 ∼ 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 K x = P i , where K x is the affinity constant of drug molecule X to the common cholinoceptor, obtained independently. 4 Linear regression of P 1 ⋍ ΔH from the data in acetonitrile over ΔS gave a satisfactory isoequilibrium plot, r 2 = 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).