(Extra)thermodynamics of the drug-receptor interaction.
A core concept in pharmacology is drug-receptor affinity, i.e., the tendency of a drug molecule to bind to one or more receptors due to the collective influence of multiple molecular forces. The estimation of affinity as a dissociation constant (reciprocal of the equilibrium constant) is extraordinarily valuable. However, elucidation of the nature of the underlying concept--i.e., what accounts for affinity--is not achievable using such a static measure. Observing how the system responds to a perturbation (e.g., to a change in temperature) reveals more fundamental information. The present review summarizes the general concepts of thermodynamic analysis applied to drug-receptor interactions and discusses 'extrathermodynamic' phenomena, such as enthalpy-entropy 'compensation'. Together, these concepts may provide insight into the nature of drug-receptor interactions, begin to elucidate the forces that underlie such interactions--and begin to define and refine more nebulous terms such as affinity.
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Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, Philadelphia, PA 19140, USA.
D000818:Animals; D004734:Energy Metabolism; D019277:Entropy; D051379:Mice; D011955:Receptors, Drug / Q000737:chemistry*; D013816:Thermodynamics
D011955:Receptors, Drug