The Evolution of Drug-Receptor Models: The Cubic Ternary Complex Model for G Protein-Coupled Receptors

One of the earliest explicit mathematical representations of drug-receptor kinetics was given by Clark 1933, Clark 1937. It was known as occupancy theory, a name that suggested that occupation of a receptor by a drug could evoke a response. To differentiate drugs that simply occupied the receptor from those that occupied and presumably changed the receptor (to produce a physiological response), a proportionality factor (intrinsic activity) was added to receptor occupancy for these latter drugs (Ariens 1954). These ideas were later extended and made more applicable to experimental pharmacology by Stephenson (1956) with the introduction of “efficacy”.