Pharmacological Receptor Theory

Abstract

This article describes the historical development of the mathematical models used to describe the interaction of drugs with receptors. It also highlights recent advances in this area over the past 20years that have moved the field forward, largely because of the technological advances that enable the observation of drug effect at a subcellular level. These models involve the description of agonism (Black/Leff operational model), antagonism (both orthosteric and allosteric) and modulation whereby drugs bind to separate sites on the protein receptor target to modify endogenous physiological response. The utilization of models rooted in drug receptor theory allows characterization of drugs through universal indices that are not affected by the sensitivity of organs in the body; this is important as data from test systems ususally is linked to the sensitivity of the test system and thus are of limited value in predicitng drug activity therapeutically. Indices derived from analyses with these pharmacodynamic models describe drug activity in terms that allow prediction of drug effect in all systems, including the therapeutic one(s).