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{{Short description|Measure of relative response to a drug}}{{cs1 config|name-list-style=vanc}} {{Expert needed|pharmacology|talk=|reason=There are mistakes in this article; efficacy and intrinsic activity are different properties|date=April 2019}}Intrinsic activity (IA) and efficacy refer to the relative ability of a drug-receptor complex to produce a maximum functional response. This must be distinguished from the affinity, which is a measure of the ability of the drug to bind to its molecular target, and the EC50, which is a measure of the potency of the drug and which is proportional to both efficacy and affinity. This use of the word “efficacy” was introduced by Stephenson (1956)JOURNAL, Stephenson RP, A modification of receptor theory, British Journal of Pharmacology and Chemotherapy, 11, 4, 379–393, December 1956, 13383117, 1510558, 10.1111/j.1476-5381.1956.tb00006.x, to describe the way in which agonists vary in the response they produce, even when they occupy the same number of receptors. High efficacy agonists can produce the maximal response of the receptor system while occupying a relatively low proportion of the receptors in that system. There is a distinction between efficacy and intrinsic activity.{{Clarify|reason=What is the distinction?|date=May 2019}}“>

Mechanism of efficacy{| class“wikitable” border“1” style@text-align:center” style@float:right;”

! Ligand! Description! colspan=“5” | % Efficacy (E)| Superagonist| Efficacy higher than the endogenous agonist| Full agonist| Efficacy equal to the endogenous agonist| Partial agonist| Efficacy less than the endogenous agonist< <| Inverse agonist| Inverse efficacy<

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Receptor antagonist#Silent antagonists>Silent antagonist| Affinity but no efficacy	=
		www.pdg.cnb.uam.es/cursos/Barcelona2002/pages/Farmac/Comput_Lab/Guia_Glaxo/chap2c.html, In vitro pharmacology: concentration-response curves, Glaxo Wellcome pharmacology guide, 2009-07-11, 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. There are actually relatively few true full agonists or silent antagonists; many compounds usually considered to be full agonists (such as DOI) are more accurately described as high efficacy partial agonists, as a partial agonist with efficacy over ≈80-90% is indistinguishable from a full agonist in most assays. Similarly many antagonists (such as naloxone) are in fact partial agonists or inverse agonists, but with very low efficacy (less than 10%). Compounds considered partial agonists tend to have efficacy in between this range. Another case is represented by silent agonists,JOURNAL, Chojnacka K, Papke RL, Horenstein NA, Synthesis and evaluation of a conditionally-silent agonist for the α7 nicotinic acetylcholine receptor, Bioorganic & Medicinal Chemistry Letters, 23, 14, 4145–4149, July 2013, 23746476, 3882203, 10.1016/j.bmcl.2013.05.039, 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.JOURNAL, Quadri M, Matera C, Silnović A, Pismataro MC, Horenstein NA, Stokes C, Papke RL, Dallanoce C, 6, Identification of α7 Nicotinic Acetylcholine Receptor Silent Agonists Based on the Spirocyclic Quinuclidine-Δ2 -Isoxazoline Scaffold: Synthesis and Electrophysiological Evaluation, ChemMedChem, 12, 16, 1335–1348, August 2017, 28494140, 5573630, 10.1002/cmdc.201700162, Intrinsic activity Intrinsic activity of a test agonist is defined as: mathrm{IA}=frac{text{maximal response to the test agonist}}{text{maximal response to full agonist}}{{r|Foreman|p=24}} Stevenson’s efficacy R. P. Stephenson (1925–2004) was a British pharmacologist.WEB,www.bps.ac.uk/about/about-pharmacology/pharmacology-hall-of-fame/articles/r-p-(-steve-)-stephenson, 2 June 2016, Pharmacology Hall of Fame, British Pharmacological Society, R P (’Steve’) Stephenson, Efficacy has historically been treated as a proportionality constant between the binding of the drug and the generation of the biological response.BOOK, Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 12th, 46, Goodman %26 Gilman%27s The Pharmacological Basis of Therapeutics, 2011, Brunton L, Chabner BA, Knollman B, Stephenson defined efficacy as: S=epBOOK,books.google.com/books?id=Y9bsUpefYW0C&pg=PA51, Textbook of Receptor Pharmacology, Second, Foreman JC, Johansen T, Gibb AJ, CRC Press, 2009, 9781439887578, {{rp|25}} where p is the proportion of agonist-bound receptors (given by the Hill equation) and S is the stimulus to the biological system.BOOK, Linderman JJ, Kinetic Modeling Approaches to Understanding Ligand Efficacy, Kenakin T, Angus JA, The Pharmacology of Functional, Biochemical, and Recombinant Receptor Systems, 2000, Springer, Berlin, 978-3-540-66124-5, 120, The response is generated by an unknown function f(S), which is assumed to be hyperbolic. This model was arguably flawed in that it did not incorporate the equilibrium between the inactivated agonist-bound-receptor and the activated agonist-bound-receptor that is shown in the del Castillo Katz model. Furchgott’s efficacy Robert F. Furchgott later improved on Stephenson’s model with the definition of efficacy, e, as S=underbrace{varepsilon[ce{R}]_{mathrm{Tot}}}_{e}cdot p where varepsilon is the intrinsic efficacy and [ce{R}]_{mathrm{Tot}} is the total concentration of receptors.Stevenson and Furchgott’s models of efficacy have been criticised and many more have been developed. The models of efficacy are shown in Bindslev (2008).BOOK, Bindslev N, Drug-Acceptor Interactions: Modeling Theoretical Tools to Test and Evaluate Experimental Equilibrium Effects, Chapter 1: Simple Agonism, 19–20, 978-91-977071-0-7, 10.4324/9781315159782, free, 2008, CRC Press, London, JOURNAL, Kirkeby H, Drug–Acceptor Interactions–Modeling theoretical tools to test and evaluate experimental equilibrium effects (Book review), Microbial Ecology in Health and Disease, 2017, 20, 4, 213, Routledge, London, 978-1-351-66057-0, 10.1080/08910600802431931, 83584731, free, References {{reflist}}{{Pharmacology}}{{Receptor agonists and antagonists}} - content above as imported from Wikipedia - "Intrinsic activity" does not exist on GetWiki (yet) - time: 2:50am EDT - Wed, May 22 2024 [ this remote article is provided by Wikipedia ] LATEST EDITS [ see all ] GETWIKI 21 MAY 2024 The Illusion of Choice Culture GETWIKI 09 JUL 2019 Eastern Philosophy History of Philosophy GETWIKI 09 MAY 2016 GetMeta:About GetWiki GETWIKI 18 OCT 2015 M.R.M. 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