Efficacy in drug receptor theory: outdated concept or under-valued tool?

In classical occupancy receptor theory, efficacy is a dimensionless proport ionality constant denoting the power of agonists to produce a pharmacologic al response. In theoretical terms, it is difficult to separate affinity and efficacy estimates of agonists for receptors, hence questioning the value of clearly flawed estimates of efficacy by conventional methods. In this pa per, the use of efficacy estimates, the limitations of the current methods to estimate efficacy, and the types of systems in which serious errors in e fficacy estimation would be expected, is discussed. Specifically, in consti tutively active receptor systems or in those where the receptor interacts w ith more than one G protein, there are theoretical objections to the use of relative maximal responses as indicators of intrinsic efficacy of agonists .