Intrinsic activity

Intrinsic activity (IA) and efficacy (Emax) refer to the relative ability of a drug-receptor complex to produce a maximum functional response.

This use of the word "efficacy" was introduced by Stephenson (1956)[1] to describe the way in which agonists vary in the response they produce, even when they occupy the same number of receptors.

Therefore, they may not be able to produce the same maximal response, even when they occupy the entire receptor population, as the efficiency of transformation of the inactive form of the drug-receptor complex to the active drug-receptor complex may not be high enough to evoke a maximal response.

[2] However, it is worth bearing in mind that these terms are relative - even partial agonists may appear as full agonists in a different system/experimental setup, as when the number of receptors increases, there may be enough drug-receptor complexes for a maximum response to be produced, even with individually low efficacy of transducing the response.

Another case is represented by silent agonists,[3] which are ligands that can place a receptor, typically an ion channel, into a desensitized state with little or no apparent activation of it, forming a complex that can subsequently generate currents when treated with an allosteric modulator.

[4] Intrinsic activity of a test agonist is defined as: R. P. Stephenson (1925–2004) was a British pharmacologist.

[6] Efficacy has historically been treated as a proportionality constant between the binding of the drug and the generation of the biological response.