Editing Inverse agonist (section)

==Examples==
Receptors for which inverse agonists have been identified include the [[GABAA|GABA<sub>A</sub>]], [[melanocortin receptor|melanocortin]], [[mu opioid receptor|mu opioid]], [[histamine receptor|histamine]] and [[beta adrenergic receptor]]s. Both [[Endogeny (biology)|endogenous]] and [[Exogeny|exogenous]] inverse agonists have been identified, as have drugs at ligand gated ion channels and at G protein-coupled receptors.

=== Ligand gated ion channel inverse agonists ===
An example of a receptor site that possesses basal activity and for which inverse agonists have been identified is the [[GABAA receptors|GABA<sub>A</sub> receptors]]. Agonists for GABA<sub>A</sub> receptors (such as [[muscimol]]) create a [[relaxant]] effect, whereas inverse agonists have [[agitation (action)|agitation]] effects (for example, [[Ro15-4513]]) or even [[convulsive]] and [[anxiogenic]] effects (certain [[beta-carboline]]s).<ref>{{cite journal|vauthors=Mehta AK, Ticku MK|date=August 1988|title=Ethanol potentiation of GABAergic transmission in cultured spinal cord neurons involves gamma-aminobutyric acid voltage-gated chloride channels|url=http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=2457076|journal=The Journal of Pharmacology and Experimental Therapeutics|volume=246|issue=2|pages=558–64|pmid=2457076|access-date=2008-04-21|archive-date=2021-05-31|archive-url=https://web.archive.org/web/20210531145604/https://jpet.aspetjournals.org/content/246/2/558.long|url-status=live}}</ref><ref>{{cite journal|vauthors=Sieghart W|date=January 1994|title=Pharmacology of benzodiazepine receptors: an update|journal=Journal of Psychiatry & Neuroscience|volume=19|issue=1|pages=24–9|pmc=1188559|pmid=8148363}}</ref>

=== G protein-coupled receptor inverse agonists ===
<!--Endogenous examples-->
Two known endogenous inverse agonists are the [[Agouti-related peptide]] (AgRP) and its associated peptide [[Agouti signalling peptide]] (ASIP). AgRP and ASIP appear naturally in humans and bind [[melanocortin receptors]] 4 and 1 ([[melanocortin 4 receptor|Mc4R]] and [[melanocortin 1 receptor|Mc1R]]), respectively, with nanomolar affinities.<ref name="pmid9450927">{{cite journal|vauthors=Ollmann MM, Lamoreux ML, Wilson BD, Barsh GS|date=February 1998|title=Interaction of Agouti protein with the melanocortin 1 receptor in vitro and in vivo|journal=Genes & Development|volume=12|issue=3|pages=316–30|doi=10.1101/gad.12.3.316|pmc=316484|pmid=9450927}}</ref>

<!--Exogenous examples-->
The [[opioid antagonist]]s [[naloxone]] and [[naltrexone]] act as [[Receptor antagonist|neutral antagonists]] of the [[mu opioid receptors]] under basal conditions, but as inverse agonists when an opioid such as [[morphine]] is bound to the same channel. 6α-naltrexo, [[6β-Naltrexol|6β-naltrexol]], 6β-naloxol, and 6β-naltrexamine acted [[Receptor antagonist|neutral antagonists]] regardless of opioid binding and caused significantly reduced withdrawal jumping when compared to [[naloxone]] and [[naltrexone]].<ref name="pmid11413242">{{cite journal|vauthors=Wang OD, Raehal KM, Bilsky EJ, Sadée W|date=June 2001|title=Inverse agonists and neutral antagonists at mu opioid receptor (MOR): possible role of basal receptor signaling in narcotic dependence |journal= Journal of Neurochemistry|volume=77|issue=3|pages=1590–600|doi=10.1046/j.1471-4159.2001.00362.x|pmid=11413242|s2cid=10026688 |doi-access=free}}</ref>

Nearly all antihistamines acting at [[H1 receptors]] and [[H2 receptors]] have been shown to be inverse agonists.<ref name=":0">{{cite journal| pmc=3195115 | pmid=22021988 | doi=10.4103/0253-7613.84947 | volume=43 | issue=5 | title=Inverse agonism and its therapeutic significance | year=2011 | journal=Indian J Pharmacol | pages=492–501 | author=Khilnani G, Khilnani AK | doi-access=free }}</ref>

The [[beta blockers]] [[carvedilol]] and [[bucindolol]] have been shown to be low level inverse agonists at [[beta adrenoceptors]].<ref name=":0" />