Non-linear coupling between receptor occupancy and biologic effect as a requirement for a higher drug efficacy

Abstract

Pharmacological drugs activate cellular functions by binding to specific receptors. Experimental observations have shown that, in many systems, the drug effect is half-maximally elicited at drug concentrations far lower than those required for saturating half the receptors. In the case of the beta-adrenergic system, such a discrepancy can be correlated with the efficacy of agonists in activating the adenylate cyclase. It is shown in this paper that, within the framework of discrepancy between binding and activation is a direct consequence of the structure of the system and is, in fact, an index of the drug efficacy.