Agonist
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2008-06-21T06:50:17Z
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{{for|other meanings of 'agonist' or 'agonism'|agonism (disambiguation)}}
[[Image:Agonist.png|thumb|Agonists]]
In [[pharmacology]] an '''agonist''' is a substance that binds to a specific [[receptor (biochemistry)|receptor]] and triggers a response in the [[cell (biology)|cell]]. It mimics the action of an [[endogenous]] [[Ligand (biochemistry)|ligand]] (such as [[hormone]] or [[neurotransmitter]]) that binds to the same receptor.
==Types== <!--selective agonist redirects here-->
'''Full agonists''' bind (have [[dissociation constant#Protein-Ligand binding|affinity]] for) and activate a receptor, displaying full [[efficacy#Pharmacology|efficacy]] at that receptor.
One example of a drug that acts as a full agonist is [[isoproterenol]] which mimics the action of [[epinephrine|adrenaline]] at [[Adrenergic receptor|β adrenoreceptor]]s. Another example is morphine, which mimics the actions of [[endorphin]]s at [[μ-opioid receptor]]s throughout the [[central nervous system]].
'''Partial agonists''' (such as [[buspirone]], [[aripiprazole]], [[buprenorphine]], or [[clozapine|norclozapine]]) also bind and activate a given receptor, but have only partial [[efficacy#Pharmacology|efficacy]] at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonistic effects - when both a full agonist and partial agonist are present, the partial agonist actually acts as a [[competitive antagonist]], competing with the full agonist for receptor occupancy and producing a net decrease in the receptor activation observed with the full agonist alone.<ref>Principles and Practice of Pharmacology for Anaesthetists By Norton Elwy Williams, Thomas Norman Calvey Published 2001 Blackwell Publishing ISBN 0632056053</ref> Clinically partial agonists can activate receptors to give a desired submaximal response when inadequate amounts of the endogenous ligand are present, or they can reduce the overstimulation of receptors when excess amounts of the endogenous ligand are present.<ref>{{cite journal |author=Zhu BT |title=Mechanistic explanation for the unique pharmacologic properties of receptor partial agonists |journal=Biomed. Pharmacother. |volume=59 |issue=3 |pages=76–89 |year=2005 |pmid=15795100 |doi=10.1016/j.biopha.2005.01.010}}</ref>
An '''[[inverse agonist]]''' is an agent which binds to the same receptor binding-site as an agonist for that receptor and reverses constitutive activity of receptors. Inverse agonists exert the opposite pharmacological effect of a receptor agonist.
A '''co-agonist''' works with other co-agonists to produce the desired effect together. NMDA receptor activation requires the binding of both of its glutamate and glycine co-agonists. An [[Receptor_antagonist|antagonist]] blocks a receptor from activation by agonists.
A '''selective agonist''' is selective for one certain type of receptor. It can additionally be of any of the aforementioned types.
A '''[[physiological agonism and antagonism|physiological agonist]]''' is a substance that creates the same bodily responses, but does not bind to the same receptor.
Receptors can be activated or inactivated either by [[endogenous]] (such as [[hormone]]s and [[neurotransmitter]]s) or [[exogenous]] (such as [[medication|drugs]]) agonists and antagonists, resulting in stimulating or inhibiting a biological response. To see how an agonist may activate a receptor see this [http://www.bio-balance.com/Graphics.htm link]
New findings that broaden the conventional definition of pharmacology demonstrate that ligands can concurrently behave as agonist ''and'' antagonists at the same receptor, depending on effector pathways. Terms that describe this phenomenon are "[[Functional Selectivity|functional selectivity]]" or "protean agonism".<ref>Kenakin T. (2001). Inverse, protean, and ligand-selective agonism: matters of receptor conformation. ''FASEB J.'' 15:598-611. PMID 11259378. [http://www.fasebj.org/cgi/content/full/15/3/598 Fulltext]</ref><ref>Urban J.D. et al. (2007). Functional selectivity and classical concepts of quantitative pharmacology. ''J. Pharmacol. Exp. Ther. 320:1-13. PMID 16803859.</ref>
==Activity==
===Potency===
The [[potency]] of an agonist is usually defined by its [[Half maximal effective concentration|EC<sub>50</sub>]] value. This can be calculated for a given agonist by determining the concentration of agonist needed to elicit half of the maximum biological response of the agonist. Elucidating an EC<sub>50</sub> value is useful for comparing the potency of drugs with similar [[efficacy#pharmacology|efficacies]] producing physiologically similar effects. The lower the EC<sub>50</sub>, the greater the potency of the agonist the lower the concentration of drug that is required to elicit the maximum biological response
===Therapeutic index===
When a drug is used therapeutically, it is important to understand the margin of safety that exists between the dose needed for the desired effect and the dose that produces unwanted and possibly dangerous side effects. This relationship, termed the [[therapeutic index]], is defined as the ratio [[Median lethal dose|LD50]]:[[Effective dose|ED50]]. In general, the narrower this margin, the more likely it is that the drug will produce unwanted effects. The therapeutic index has many limitations, notably the fact that LD50 cannot be measured in humans and, when measured in animals, is a poor guide to the likelihood of unwanted effects in humans. Nevertheless, the therapeutic index emphasizes the importance of the margin of safety, as distinct from the potency, in determining the usefulness of a drug.
==Etymology==
From the [[Ancient Greek language|Greek]] '''αγωνιστής''' (agōnistēs), contestant; champion; rival < '''αγων''' (agōn), contest, combat; exertion, struggle < '''αγω''' (agō), I lead, lead towards, conduct; drive
==See also==
* [[Receptor theory]]
* [[Inverse agonist]]
* [[Receptor antagonist]]
* [[Excitatory postsynaptic potential]]
* [[Allosteric regulation#Pharmacology|Allosteric modulator]]
* [[efficacy#pharmacology|Intrinsic activity]]
* [[Dose response curve]]
==References==
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[[Category:Medical terms]]
[[Category:Pharmacology]]
[[Category:Physiology]]
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