Binding theory receptor occupancy

Pharmacodynamics describes the time course and the magnitude of pharmacological response of drugs. Based on the classic receptor-occupancy theory, after drug molecules reach the target biophase, it binds to the receptors to form the drug-receptor complex to exert pharmacological response (Fig. 2). 

The classical occupation theory of Clark rests on the assumption that drugs interact with independent binding sites and activate them, resulting in a biological response that is proportional to the amount of drug-receptor complex formed. The response ceases when this complex dissociates. Assuming a bimolecular reaction, one can write... 

Another alternative to occupancy theory is rate theory. Rate theory was developed by Paton through examination of receptors that bind stimulants.30 Paton proposed that a response is caused by the act of binding, not the state of being bound or free (Scheme 5.8). This seemingly subtle difference shifts the theory away from KD and toward kon and fcoff, the rate constants of association and dissociation. Interestingly, at equilibrium, KD is equal to koa/kon (Equations 5.19-5.21). For this reason, occupancy and rate theory are closely related. 

Receptor inactivation theory, initially proposed by Gosselin in 1977 has been widely disseminated by Kenakin (35)and to some degree is based on the two-state model originally proposed by Katz and Thesleff (41) for ion channels, specifically the Torpedo nicotinic receptor. where the multimeric receptor exists in active and inactive states, with ligand binding altering the equilibrium between these two states. Receptor inactivation theory reflects a synthesis of both occupancy and rate theories providing an alternative consideration for the study of the RL interaction. 

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