Thermodynamic analysis of the drug-receptor interaction

Thermodynamic analysis of pharmacologic data potentially offers an insight into the molecular events underlying drug-receptor interactions not obtainable by other techniques. Embodied in thermodynamics are the laws governing the interconvertibility of heat and work and, hence, it is a particularly apt framework for the analysis of the transduction of information from ligand to biological tissue during the initiation of a drug effect. Implicit in thermodynamic analysis of pharmacologic data is quantitative measurement of the driving forces involved in the drug-receptor interaction (in place of less precise terms such as "affinity"). In addition, the cautious interpretation of thermodynamic analysis can give clues to the underlying mechanisms of the drug-receptor interaction that is beyond the resolving power of other parameters, such as the dissociation constant. The present review is an attempt to identify repsresentative reports that have overtly analyzed pharmacologic data with thermodynamic analysis, to summarize the findings within and across studies (particularly regarding enthapy - versus entropy-driven binding of agonists and antagonists), to point out and address some apparent inconsistencies that can arise, and to consider the application of thermodynamic analysis to data obtained using isolated tissue preparations.