Up/Down: A New Method for Determining Agonist Properties

Abstract

Quantitation of agonist concentration-response curves yields information regarding the agonist potency and maximum effect. The potency is well known to be dependent on both drug and tissue factors (agonist efficacy and affinity, tissue receptor reserve and stimulus-response coupling efficiency). The agonist maximum effect is a function of the agonist efficacy and the tissue properties of receptor reserve and stimulus-response coupling efficiency. However, when the agonist has sufficient efficacy to maximally activate the tissue, the maximum effect of the agonist becomes a property only of the tissue: the tissue maximum response. A new protocol has been devised that allows the generation of extended concentration-response curves that overcome the tissue maximum response as a constraint on the maximum measured effect of an agonist. This protocol has been called the up/down protocol.