Prescient Indices of Activity: The Application of Functional System Sensitivity to Measurement of Drug Effect.

Through pharmacological procedures, indices of drug activity can be obtained that transcend the systems in which they are measured. If (i) affinity, (ii) efficacies, (iii) orthosteric versus allosteric interaction, and (iv) rate of receptor offset can be determined, activity can be predicted in all systems. This can yield more detailed profiles (fingerprints) of efficacy to better define the required activities of follow-up molecules should the original candidates fail in the clinic. The use of functional assays of varying sensitivity is a major tool in the lead optimization process and the observation of candidate molecule profiles in multiple functional assays can reveal all properties of candidate molecules. In this review, the different indices for agonists, antagonists, and allosteric modulators are defined while highlighting the application of functional assays in deriving these indices.