View source for 5-HT2A receptor

{{DISPLAYTITLE:5-HT<sub>2A</sub> receptor}}
{{PBB|geneid=3356}}
The mammalian '''5-HT<sub>2A</sub> receptor''' is a subtype of the 5-HT<sub>2</sub> receptor that belongs to the [[serotonin receptor]] family and is a [[GPCR|G protein-coupled receptor]] (GPCR).<ref name="pmid8035173">{{cite journal| author = Cook EH, Fletcher KE, Wainwright M, Marks N, Yan SY, Leventhal BL| title = Primary structure of the human platelet serotonin 5-HT<sub>2</sub> receptor: identity with frontal cortex serotonin 5-HT<sub>2A</sub> receptor| journal = J. Neurochem.| volume = 63| issue = 2| pages = 465–9| year = 1994| month = August| pmid = 8035173| doi = 10.1046/j.1471-4159.1994.63020465.x| url = }}</ref> This is the main excitatory receptor subtype among the [[GPCR]]s for [[serotonin]] (5-HT), although 5-HT<sub>2A</sub> may also have an inhibitory effect{{Citation needed|date=February 2009}} on certain areas such as the [[visual cortex]] and the [[orbitofrontal cortex]]. This receptor was given importance first as the target of [[psychedelic]] drugs like [[LSD]]. Later it came back to prominence because it was also found to be mediating, at least partly, the action of many [[antipsychotic]] drugs, especially the [[atypical antipsychotic|atypical]] ones. 

5-HT<sub>2A</sub> also happens to be a necessary receptor for the spread of the human [[polyoma virus]] called [[JC virus]].<ref name="pmid15550673">{{cite journal| author = Elphick GF, Querbes W, Jordan JA, Gee GV, Eash S, Manley K, Dugan A, Stanifer M, Bhatnagar A, Kroeze WK, Roth BL, Atwood WJ| title = The human polyomavirus, JCV, uses serotonin receptors to infect cells| journal = Science| volume = 306| issue = 5700| pages = 1380–3| year = 2004| pmid = 15550673| doi = 10.1126/science.1103492 }}</ref>

== History ==

Serotonin receptors were split into two classes by Gaddum and Picarelli when it was discovered that some of the serotonin-induced changes in the [[Gut (zoology)|gut]] could be blocked by [[morphine]], whilst the remainder of the response was inhibited by [[Phenoxybenzamine|dibenzyline]] leading to the naming of M and D receptors respectively.  5-HT<sub>2A</sub> is thought to correspond to what was originally described as D subtype of 5-HT receptors by Gaddum and Picarelli.<ref name="isbn0-07-142280-3">{{cite book| author = Sanders-Bush E, Mayer SE| authorlink =| editor = Brunton LL, Lazo JS, Parker K| others =| title = Goodman & Gilman's the Pharmacological Basis of Therapeutics| edition = 11th| language =| publisher = McGraw-Hill| location = New York| year = 2006| origyear =| pages =| chapter = Chapter 11: 5-Hydroxytryptamine (Serotonin): Receptor Agonists and Antagonists| quote =| isbn = 0-07-142280-3| oclc =| doi =| url =| accessdate = }}</ref> In the pre-molecular-cloning era when [[radioligand]] binding and displacement was the only major tool, spiperone and LSD were shown to label two different serotonin receptors, and neither of them displaced morphine, leading to naming of the [[5-HT1 receptor|5-HT<sub>1</sub>]], [[5-HT2 receptor|5-HT<sub>2</sub>]] and [[5-HT3 receptor|5-HT<sub>3</sub>]] receptors, corresponding to high affinity sites from [[LSD]], [[spiperone]] and morphine respectively.{{Citation needed|date=March 2009|reason=there was a "(?)" here}} Later it was shown that the 5-HT<sub>2</sub> was very close to 5-HT<sub>1C</sub> and thus were clubbed together, renaming the 5-HT<sub>2</sub> into 5-HT<sub>2A</sub>. Thus the 5-HT<sub>2</sub> receptor family is composed of three separate molecular entities: the 5-HT<sub>2A</sub> (erstwhile 5-HT<sub>2</sub> or D), the 5-HT<sub>2B</sub> (erstwhile 5-HT<sub>2F</sub>) and the 5-HT<sub>2C</sub> (erstwhile 5-HT<sub>1C</sub>) receptors.<ref name="Hoyer_2002">{{cite journal| author = Hoyer D, Hannon JP, Martin GR| title = Molecular, pharmacological and functional diversity of 5-HT receptors| journal = Pharmacol. Biochem. Behav.| volume = 71| issue = 4| pages = 533–54| year = 2002| month = April| pmid = 11888546| doi = 10.1016/S0091-3057(01)00746-8| url =| issn = }}</ref>

== Distribution ==

5-HT<sub>2A</sub> is expressed widely throughout the [[central nervous system]] (CNS).
It is expressed near most of the serotoninergic terminal rich areas, including [[neocortex]] (mainly [[prefrontal]], [[parietal cortex|parietal]], and [[somatosensory cortex]]) and the [[olfactory tubercle]]. Especially high concentrations of this receptor on the [[apical dendrite]]s of [[pyramidal cell]]s in [[layer V]] of the cortex may modulate cognitive processes,<ref name="pmid10216183">{{cite journal| author = Aghajanian GK, Marek GJ| title = Serotonin, via 5-HT2A receptors, increases EPSCs in layer V pyramidal cells of prefrontal cortex by an asynchronous mode of glutamate release| journal = Brain Res.| volume = 825| issue = 1-2| pages = 161–71| year = 1999| month = April| pmid = 10216183| doi = 10.1016/S0006-8993(99)01224-X| url =| issn = }}</ref><ref name="pmid11672605">{{cite journal| author = Marek GJ, Wright RA, Gewirtz JC, Schoepp DD| title = A major role for thalamocortical afferents in serotonergic hallucinogen receptor function in the rat neocortex| journal = Neuroscience| volume = 105| issue = 2| pages = 379–92| year = 2001| pmid = 11672605| doi = 10.1016/S0306-4522(01)00199-3| url =| issn = }}</ref><ref name="pmid16277612">{{cite journal| author = Bortolozzi A, Díaz-Mataix L, Scorza MC, Celada P, Artigas F| title = The activation of 5-HT receptors in prefrontal cortex enhances dopaminergic activity| journal = J. Neurochem.| volume = 95| issue = 6| pages = 1597–607| year = 2005| month = December| pmid = 16277612| doi = 10.1111/j.1471-4159.2005.03485.x| url =| issn = }}</ref> by enhancing [[glutamate]] release followed by a complex range of interactions with the [[5-HT1A receptor|5-HT<sub>1A</sub>]],<ref name="pmid14754868">{{cite journal| author = Amargós-Bosch M, Bortolozzi A, Puig MV, Serrats J, Adell A, Celada P, Toth M, Mengod G, Artigas F| title = Co-expression and in vivo interaction of serotonin1A and serotonin2A receptors in pyramidal neurons of prefrontal cortex| journal = Cereb. Cortex| volume = 14| issue = 3| pages = 281–99| year = 2004| month = March| pmid = 14754868| doi = 10.1093/cercor/bhg128| url =| issn = }}</ref> [[GABAA receptor|GABA<sub>A</sub>]],<ref name="pmid11517239">{{cite journal| author = Feng J, Cai X, Zhao J, Yan Z| title = Serotonin receptors modulate GABA(A) receptor channels through activation of anchored protein kinase C in prefrontal cortical neurons| journal = J. Neurosci.| volume = 21| issue = 17| pages = 6502–11| year = 2001| month = September| pmid = 11517239| doi =| url = http://www.jneurosci.org/cgi/content/abstract/21/17/6502| issn = }}</ref> [[Adenosine A1 receptor|adenosine A<sub>1</sub>]],<ref>{{cite journal| author = Marek GJ| title = Activation of adenosine(1) (A(1)) receptors suppresses head shakes induced by a serotonergic hallucinogen in rats| journal = Neuropharmacology| volume =56| issue =8| pages =1082–7| year = 2009| month = March| pmid = 19324062| doi = 10.1016/j.neuropharm.2009.03.005| url =| issn =| pmc = 2706691 }}</ref> [[AMPA receptor|AMPA]],<ref>{{cite journal| author = Zhang C, Marek GJ| title = AMPA receptor involvement in 5-hydroxytryptamine2A receptor-mediated pre-frontal cortical excitatory synaptic currents and DOI-induced head shakes| journal = Progress in Neuro-psychopharmacology & Biological Psychiatry| volume = 32| issue = 1| pages = 62–71| year = 2008| month = January| pmid = 17728034| doi = 10.1016/j.pnpbp.2007.07.009| url =| issn = }}</ref> [[Metabotropic glutamate receptor#Classification|mGluR<sub>2/3</sub>]],<ref>{{cite journal| author = Gewirtz JC, Marek GJ| title = Behavioral evidence for interactions between a hallucinogenic drug and group II metabotropic glutamate receptors| journal = Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology| volume = 23| issue = 5| pages = 569–76| year = 2000| month = November| pmid = 11027922| doi = 10.1016/S0893-133X(00)00136-6| url =| issn = }}</ref> [[Metabotropic glutamate receptor 5|mGlu5]],<ref name="pmid18621097">{{cite journal| author = Marek GJ, Zhang C| title = Activation of metabotropic glutamate 5 (mGlu5) receptors induces spontaneous excitatory synaptic currents in layer V pyramidal cells of the rat prefrontal cortex| journal = Neurosci. Lett.| volume = 442| issue = 3| pages = 239–43| year = 2008| month = September| pmid = 18621097| doi = 10.1016/j.neulet.2008.06.083| url =| issn =| pmc = 2677702 }}</ref> and [[Hypocretin (orexin) receptor 2|OX<sub>2</sub>]] receptors.<ref name="pmid17656637">{{cite journal| author = Lambe EK, Liu RJ, Aghajanian GK| title = Schizophrenia, hypocretin (orexin), and the thalamocortical activating system| journal = Schizophr Bull| volume = 33| issue = 6| pages = 1284–90| year = 2007| month = November| pmid = 17656637| doi = 10.1093/schbul/sbm088| url =| issn =| pmc = 2779889 }}</ref><ref name="pmid18172209">{{cite journal| author = Liu RJ, Aghajanian GK| title = Stress blunts serotonin- and hypocretin-evoked EPSCs in prefrontal cortex: role of corticosterone-mediated apical dendritic atrophy| journal = Proc. Natl. Acad. Sci. U.S.A.| volume = 105| issue = 1| pages = 359–64| year = 2008| month = January| pmid = 18172209| pmc = 2224217| doi = 10.1073/pnas.0706679105| url =| issn = }}</ref> In the rat cerebellum, the protein has also been found in the [[Golgi cell]]s of the [[granular layer]],<ref name="pmid12084412">{{cite journal| author = Geurts FJ, De Schutter E, Timmermans JP| title = Localization of 5-HT<sub>2A</sub>, 5-HT<sub>3</sub>, 5-HT<sub>5A</sub> and 5-HT<sub>7</sub> receptor-like immunoreactivity in the rat cerebellum| journal = Journal of chemical neuroanatomy| volume = 24| issue = 1| pages = 65–74| year = 2002| month = June| pmid = 12084412| doi = 10.1016/S0891-0618(02)00020-0| url = }}</ref> and in the [[Purkinje cell]]s.<ref name="pmid9756362">{{cite journal| author = Maeshima T, Shutoh F, Hamada S, Senzaki K, Hamaguchi-Hamada K, Ito R, Okado N| title = Serotonin2A receptor-like immunoreactivity in rat cerebellar Purkinje cells| journal = Neurosci. Lett.| volume = 252| issue = 1| pages = 72–4| year = 1998| month = August| pmid = 9756362| doi = 10.1016/S0304-3940(98)00546-1| url =| issn = }}</ref><ref name="pmid15567478">{{cite journal| author = Maeshima T, Shiga T, Ito R, Okado N| title = Expression of serotonin2A receptors in Purkinje cells of the developing rat cerebellum| journal = Neurosci. Res.| volume = 50| issue = 4| pages = 411–7| year = 2004| month = December| pmid = 15567478| doi = 10.1016/j.neures.2004.08.010| url =| issn = }}</ref>

In the periphery, it is highly expressed in [[platelets]] and many cell types of the [[cardiovascular]]system, in [[fibroblast]]s, and in neurons of the peripheral nervous system.

== Signaling cascade ==

The 5-HT<sub>2A</sub> receptor is known primarily to couple to the Gα<sub>q</sub> signal transduction pathway. Upon receptor stimulation with agonist, Gα<sub>q</sub> and β-γ subunits dissociate to initiate downstream effector pathways.  Gα<sub>q</sub> stimulates [[phospholipase C]] (PLC) activity, which subsequently promotes the release of [[diglyceride|diacylglycerol]]&nbsp;(DAG) and [[inositol triphosphate]]&nbsp;(IP3), which in turn stimulate [[protein kinase C]]&nbsp;(PKC) activity and [[Ca2+|Ca<sup>2+</sup>]] release.<ref name="pmid16803859">{{cite journal| author = Urban JD, Clarke WP, von Zastrow M, Nichols DE, Kobilka B, Weinstein H, Javitch JA, Roth BL, Christopoulos A, Sexton PM, Miller KJ, Spedding M, Mailman RB| title = Functional selectivity and classical concepts of quantitative pharmacology| journal = J. Pharmacol. Exp. Ther.| volume = 320| issue = 1| pages = 1–13| year = 2007| pmid = 16803859| doi = 10.1124/jpet.106.104463 }}</ref>

There are many additional signal cascade components that include the formation of [[arachidonic acid]] through [[PLA2]] activity, activation of [[PLD]], [[Rho family of GTPases|Rho]]/[[Rho kinase]], and [[Extracellular signal-regulated kinases|ERK]] pathway activation initiated by agonist stimulation of the receptor.{{Citation needed|date=November 2007}}

== Effects ==

Physiological processes mediated by the receptor include:
* CNS: neuronal excitation, behavioural effects, learning, anxiety
* smooth muscle: contraction (in [[gastrointestinal tract]] & [[bronchi]])
* [[vasoconstriction]] / [[vasodilatation]]
* platelets: [[platelet aggregation|aggregation]]
*Activation of the 5-HT<sub>2A</sub> receptor with DOI produces superpotent [[anti-inflammatory]] effects in cardiovascular related tissues, as well as potent anti-inflammatory effects in non-cardiovascular tissues. Other 5-HT<sub>2A</sub> agonists like LSD also have potent anti-inflammatory effects against [[TNF-alpha]]-induced [[inflammation]].<ref>{{cite journal| author = Yu B, Becnel J, Zerfaoui M, Rohatgi R, Boulares AH, Nichols CD| title = Serotonin 5-hydroxytryptamine(2A) receptor activation suppresses tumor necrosis factor-_-induced inflammation with extraordinary potency| journal = J. Pharmacol. Exp. Ther.| volume = 327| issue = 2| pages = 316–23| year = 2008| month = November| pmid = 18708586| doi = 10.1124/jpet.108.143461| url =  }}</ref>

== Ligands ==
=== Agonists ===

Activation of the 5-HT<sub>2A</sub> [[receptor (biochemistry)|receptor]] is necessary for the effects of the "classic" [[psychedelic]]s like [[LSD]], [[psilocin]] and [[mescaline]], which act as full or partial [[agonists]] at this receptor, and represent the three main classes of 5-HT<sub>2A</sub> agonists, the [[ergoline]]s, [[tryptamine]]s and [[phenethylamine]]s, respectively. A very large family of derivatives from these three classes has been developed, and their [[structure-activity relationship]]s have been extensively researched.<ref>Nichols DE. Hallucinogens. ''Pharmacology and Therapeutics''. 2004 Feb;101(2):131-81. PMID 14761703</ref><ref>Blaazer AR, Smid P, Kruse CG. Structure-activity relationships of phenylalkylamines as agonist ligands for 5-HT<sub>2A</sub> receptors. ''ChemMedChem''. 2008 Sep;3(9):1299-309. PMID 18666267</ref> Agonists acting at  5-HT<sub>2A</sub> receptors located on the [[apical dendrite]]s of [[pyramidal cell]]s within regions of the [[prefrontal cortex]] are believed to mediate hallucinogenic activity. 

==== Full agonists ====

* [[2,5-Dimethoxy-4-iodoamphetamine|(R)-DOI]]
* [[25I-NBOH|N-(2-hydroxybenzyl)-2C-I]] and [[25I-NBOMe|its 2-methoxy-analog]]<ref name="pmid17000863">{{cite journal
| author = Braden MR, Parrish JC, Naylor JC, [[David E. Nichols|Nichols DE]]
| title = Molecular interaction of serotonin 5-HT<sub>2A</sub> receptor residues Phe339(6.51) and Phe340(6.52) with superpotent N-benzyl phenethylamine agonists| journal = Mol. Pharmacol.| volume = 70| issue = 6| pages = 1956–64| year = 2006| pmid = 17000863| doi = 10.1124/mol.106.028720 }}</ref> 
* [[TCB-2]]<ref name="pmid16970404">{{cite journal| author = McLean TH, Parrish JC, Braden MR, Marona-Lewicka D, Gallardo-Godoy A, [[David E. Nichols|Nichols DE]]| title = 1-Aminomethylbenzocycloalkanes: conformationally restricted hallucinogenic phenethylamine analogues as functionally selective 5-HT<sub>2A</sub> receptor agonists| journal = Journal of medicinal chemistry| volume = 49| issue = 19| pages = 5794–803| year = 2006| month = September| pmid = 16970404| doi = 10.1021/jm060656o| url =  }}</ref> 
* [[Br-DFLY]].<ref name="pmid11300881">{{cite journal| author = Chambers JJ, Kurrasch-Orbaugh DM, Parker MA, Nichols DE| title = Enantiospecific synthesis and pharmacological evaluation of a series of super-potent, conformationally restricted 5-HT(2A/2C) receptor agonists| journal = Journal of Medicinal  Chemistry| volume = 44| issue = 6| pages = 1003–10| year = 2001| month = March| pmid = 11300881| doi = 10.1021/jm000491y| url =  }}</ref>

==== Partial agonists ====

[[Methysergide]], a congener of [[methylergonovine]], used in treatment of [[migraine]] blocks 5-HT<sub>2A</sub> and 5-HT<sub>2C</sub> receptors, but sometimes acts as partial agonist, in some preparations.

==== Peripherally selective agonists ====

One effect of 5-HT<sub>2A</sub> receptor activation is a reduction in intraocular pressure, and so 5-HT<sub>2A</sub> agonists can be useful for the treatment of [[glaucoma]]. This has led to the development of compounds such as [[AL-34662]] that are hoped to reduce pressure inside the eyes but without crossing the [[blood-brain barrier]] and producing hallucinogenic side effects.<ref name="pmid17341144">{{cite journal| author = Sharif NA, McLaughlin MA, Kelly CR| title = AL-34662: a potent, selective, and efficacious ocular hypotensive serotonin-2 receptor agonist| journal = Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics| volume = 23| issue = 1| pages = 1–13| year = 2007| month = February| pmid = 17341144| doi = 10.1089/jop.2006.0093| url =  }}</ref> Animal studies with this compound showed it to be free of hallucinogenic effects at doses up to 30&nbsp;mg/kg, although several of its more lipophilic analogues did produce the head twitch response known to be characteristic of hallucinogenic effects in rodents.<ref name="pmid16392816">{{cite journal| author = May JA, Dantanarayana AP, Zinke PW, McLaughlin MA, Sharif NA| title = 1-((S)-2-aminopropyl)-1H-indazol-6-ol: a potent peripherally acting 5-HT<sub>2</sub> receptor agonist with ocular hypotensive activity| journal = Journal of Medicinal Chemistry| volume = 49| issue = 1| pages = 318–28| year = 2006| month = January| pmid = 16392816| doi = 10.1021/jm050663x| url =  }}</ref>

=== Silent antagonists ===

* Although [[ergot]] alkaloids are mostly nonspecific 5-HT receptor antagonists, a few ergot derivatives such as [[metergoline]] bind preferentially to members of the 5-HT<sub>2</sub> receptor family.

* [[Ketanserin]], the prototypic 5-HT<sub>2</sub> receptor antagonist potently blocks 5-HT<sub>2A</sub>receptors, less potently blocks 5-HT<sub>2C</sub> receptors, and has no significant effect on 5-HT<sub>3</sub> or 5-HT<sub>4</sub> receptors or any members of the 5-HT<sub>1</sub> receptor family.{{Citation needed|date=May 2009}} Thus discovery of Ketanserin was a landmark in the pharmacology of 5-HT<sub>2</sub> receptors. Ketanserin, though capable of blocking 5-HT induced platelet adhesion, however does not mediate its well known antihypertensive action through 5-HT<sub>2</sub> receptor family, but through its high affinity for alpha<sub>1</sub> adrenergic receptors. It also has high affinity for H<sub>1</sub> histaminergic receptors equal to that at 5-HT<sub>2A</sub> receptors.  Compounds chemically related to ketanserin such as [[ritanserin]] are more selective 5-HT<sub>2A</sub> receptor antagonists with low affinity for alpha-adrenergic receptors. However, ritanserin, like most other 5-HT<sub>2A</sub> receptor antagonists, also potently inhibits 5-HT<sub>2C</sub> receptors.  

* [[Nefazodone]] operates by blocking post-synaptic serotonin type-2A receptors and to a lesser extent by inhibiting pre-synaptic serotonin and norepinephrine (noradrenaline) reuptake.

* [[Atypical antipsychotic]] drugs like [[clozapine]], [[olanzapine]], [[quetiapine]], [[risperidone]] are relatively potent antagonists of 5-HT<sub>2A</sub> as are some of the lower potency old generation/typical antipsychotics. Other antagonists are [[MDL-100,907]] (prototype of another new series of 5-HT<sub>2A</sub>antagonists) and [[cyproheptadine]].

* [[Pizotifen]] is a non-selective antagonist.<ref name="Rang187"> {{cite book|author=Rang, H. P.|title=Pharmacology|publisher=Churchill Livingstone|location=Edinburgh|year=2003|pages=|isbn=0-443-07145-4|oclc=|doi=}} Page 187</ref>

* 2-alkyl-4-aryl-tetrahydro-pyrimido-azepines are subtype selective antagonists (35g: 60-fold).<ref name="pmid18282705">{{cite journal| author = Shireman BT, Dvorak CA, Rudolph DA, Bonaventure P, Nepomuceno D, Dvorak L, Miller KL, Lovenberg TW, Carruthers NI| title = 2-Alkyl-4-aryl-pyrimidine fused heterocycles as selective 5-HT<sub>2A</sub> antagonists| journal = Bioorganic & medicinal chemistry letters| volume = 18| issue = 6| pages = 2103–8| year = 2008| month = March| pmid = 18282705| doi = 10.1016/j.bmcl.2008.01.090| url =  }}</ref>

* [[9-Aminomethyl-9,10-dihydroanthracene|AMDA]] and related derivatives are another family of selective 5-HT<sub>2A</sub> antagonists.<ref name="pmid10513561">{{cite journal| author = Westkaemper RB, Runyon SP, Bondarev ML, Savage JE, Roth BL, Glennon RA| title = 9-(Aminomethyl)-9,10-dihydroanthracene is a novel and unlikely 5-HT<sub>2A</sub> receptor antagonist| journal = Eur. J. Pharmacol.| volume = 380| issue = 1| pages = R5–7| year = 1999| month = September| pmid = 10513561| doi = 10.1016/S0014-2999(99)00525-7| url =  }}</ref><ref name="pmid12052195">{{cite journal| author = Westkaemper RB, Glennon RA| title = Application of ligand SAR, receptor modeling and receptor mutagenesis to the discovery and development of a new class of 5-HT<sub>2A</sub> ligands| journal = Curr Top Med Chem| volume = 2| issue = 6| pages = 575–98| year = 2002| month = June| pmid = 12052195| doi = 10.2174/1568026023393741| url = }}</ref><ref name="pmid14660041">{{cite journal| author = Peddi S, Roth BL, Glennon RA, Westkaemper RB| title = Spiro[9,10-dihydroanthracene]-9,3'-pyrrolidine-a structurally unique tetracyclic 5-HT<sub>2A</sub> receptor antagonist| journal = Eur. J. Pharmacol.| volume = 482| issue = 1-3| pages = 335–7| year = 2003| month = December| pmid = 14660041| doi = 10.1016/j.ejphar.2003.09.059| url =  }}</ref><ref name="pmid18847250">{{cite journal| author = Runyon SP, Mosier PD, Roth BL, Glennon RA, Westkaemper RB| title = Potential modes of interaction of 9-aminomethyl-9,10-dihydroanthracene (AMDA) derivatives with the 5-HT<sub>2A</sub> receptor: a ligand structure-affinity relationship, receptor mutagenesis and receptor modeling investigation| journal = J. Med. Chem.| volume = 51| issue = 21| pages = 6808–28| year = 2008| month = November| pmid = 18847250| doi = 10.1021/jm800771x| url =  }}</ref><ref name="pmid17314044">{{cite journal| author = Wilson KJ, van Niel MB, Cooper L, Bloomfield D, O'Connor D, Fish LR, MacLeod AM| title = 2,5-Disubstituted pyridines: the discovery of a novel series of 5-HT<sub>2A</sub> ligands| journal = Bioorg. Med. Chem. Lett.| volume = 17| issue = 9| pages = 2643–8| year = 2007| month = May| pmid = 17314044| doi = 10.1016/j.bmcl.2007.01.098| url =  }}</ref>

=== Inverse agonists ===

* [[AC-90179]] - potent and selective inverse agonist at 5-HT<sub>2A</sub>, also 5-HT<sub>2C</sub> antagonist.<ref name="pmid11561089">{{cite journal| author = Weiner DM, Burstein ES, Nash N, Croston GE, Currier EA, Vanover KE, Harvey SC, Donohue E, Hansen HC, Andersson CM, Spalding TA, Gibson DF, Krebs-Thomson K, Powell SB, Geyer MA, Hacksell U, Brann MR| title = 5-hydroxytryptamine2A receptor inverse agonists as antipsychotics| journal = J. Pharmacol. Exp. Ther.| volume = 299| issue = 1| pages = 268–76| year = 2001| month = October| pmid = 11561089| doi =| url = http://jpet.aspetjournals.org/cgi/content/abstract/299/1/268| issn = }}</ref><ref name="pmid15102927">{{cite journal| author = Vanover KE, Harvey SC, Son T, Bradley SR, Kold H, Makhay M, Veinbergs I, Spalding TA, Weiner DM, Andersson CM, Tolf BR, Brann MR, Hacksell U, Davis RE| title = Pharmacological characterization of AC-90179 [2-(4-methoxyphenyl)-N-(4-methyl-benzyl)-N-(1-methyl-piperidin-4-yl)-acetamide hydrochloride]: a selective serotonin 2A receptor inverse agonist| journal = J. Pharmacol. Exp. Ther.| volume = 310| issue = 3| pages = 943–51| year = 2004| month = September| pmid = 15102927| doi = 10.1124/jpet.104.066688| url =  }}</ref>

* [[APD-125]] - selective 5-HT<sub>2A</sub> inverse agonist developed by [[Arena Pharmaceuticals]] for the treatment of insomnia. APD-125 was shown to be effective and well tolerated in clinical trials,<ref>Rosenberg R, Seiden DJ, Hull SG, Erman M, Schwartz H, Anderson C, Prosser W, Shanahan W, Sanchez M, Chuang E, Roth T. APD125, a selective serotonin 5-HT<sub>2A</sub> receptor inverse agonist, significantly improves sleep maintenance in primary insomnia. ''Sleep''. 2008 Dec 1;31(12):1663-71. PMID 19090322</ref> but development of APD-125 was halted in December 2008 because the substance did not meet the trial's endpoints.<ref>[http://www.arenapharm.com/wt/page/apd125.html APD125 for Insomnia]</ref>

* [[Eplivanserin]] ([[Sanofi Aventis]]), a sleeping pill that reached phase II trials (but for which the application for approval was withdrawn), acts as a selective 5-HT<sub>2A</sub> inverse agonist.

* [[Nelotanserin]]

* [[Pimavanserin|Pimavanserin (ACP-103)]] - more selective than AC-90179, orally active, antipsychotic ''in vivo'', now in human clinical trials.<ref name="pmid16469866">{{cite journal| author = Vanover KE, Weiner DM, Makhay M, Veinbergs I, Gardell LR, Lameh J, Del Tredici AL, Piu F, Schiffer HH, Ott TR, Burstein ES, Uldam AK, Thygesen MB, Schlienger N, Andersson CM, Son TY, Harvey SC, Powell SB, Geyer MA, Tolf BR, Brann MR, Davis RE| title = Pharmacological and behavioral profile of N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl) carbamide (2R,3R)-dihydroxybutanedioate (2:1) (ACP-103), a novel 5-hydroxytryptamine(2A) receptor inverse agonist| journal = J. Pharmacol. Exp. Ther.| volume = 317| issue = 2| pages = 910–8| year = 2006| month = May| pmid = 16469866| doi = 10.1124/jpet.105.097006| url =  }}</ref><ref name="pmid17519387">{{cite journal| author = Gardell LR, Vanover KE, Pounds L, Johnson RW, Barido R, Anderson GT, Veinbergs I, Dyssegaard A, Brunmark P, Tabatabaei A, Davis RE, Brann MR, Hacksell U, Bonhaus DW| title = ACP-103, a 5-hydroxytryptamine 2A receptor inverse agonist, improves the antipsychotic efficacy and side-effect profile of haloperidol and risperidone in experimental models| journal = J. Pharmacol. Exp. Ther.| volume = 322| issue = 2| pages = 862–70| year = 2007| month = August| pmid = 17519387| doi = 10.1124/jpet.107.121715| url =  }}</ref><ref name="pmid18534670">{{cite journal| author = Vanover KE, Betz AJ, Weber SM, Bibbiani F, Kielaite A, Weiner DM, Davis RE, Chase TN, Salamone JD| title = A 5-HT<sub>2A</sub> receptor inverse agonist, ACP-103, reduces tremor in a rat model and levodopa-induced dyskinesias in a monkey model| journal = Pharmacol. Biochem. Behav.| volume = 90| issue = 4| pages = 540–4| year = 2008| month = October| pmid = 18534670| doi = 10.1016/j.pbb.2008.04.010| url =| pmc = 2806670  }}</ref><ref name="pmid19040345">{{cite journal| author = Abbas A, Roth BL| title = Pimavanserin tartrate: a 5-HT<sub>2A</sub> inverse agonist with potential for treating various neuropsychiatric disorders| journal = Expert Opin Pharmacother| volume = 9| issue = 18| pages = 3251–9| year = 2008| month = December| pmid = 19040345| doi = 10.1517/14656560802532707| url =  }}</ref>

=== Examples ===

{| class="wikitable" 
! [[Agonist]]s
! [[Receptor antagonist|Antagonist]]s
|-
| valign="top"|
*[[α-methyl-5-HT]]    
*[[Alpha-Methyltryptamine|AMT]]
*[[Dimethyltryptamine|DMT]]
*[[LSD]]
*[[mescaline]]
*[[psilocin]]
*[[TCB-2]]
| valign="top"|
*[[cyproheptadine]]
*[[ketanserin]]
*[[mirtazapine]]
*[[nefazodone]]
*[[pizotifen]]
*[[trazodone]]
*[[atypical antipsychotics]]
|-
|}

=== Functional selectivity ===

5-HT<sub>2A</sub>-receptor [[Ligand (biochemistry)|ligands]] may differentially activate the [[signal transduction|transductional pathways]] ([[#Signalling Cascade|see above]]). Studies evaluated the activation of two [[Effector (biology)|effectors]], [[Phospholipase C|PLC]] and [[Phospholipase A2|PLA2]], by means of their [[second messenger]]s. Compounds displaying more pronounced [[functional selectivity]] are [[Dimethoxyamphetamine#2,5-DMA|2,5-DMA]] and [[2C-N]]. The former induces [[Inositol triphosphate|IP]] accumulation without activating the PLA2 mediated response, while the latter elicits [[Arachidonic acid|AA]] release without activating the PLC mediated response.<!--other pathways were not examined in the reference--><ref name="pmid17337633">{{cite journal| author = Moya PR, Berg KA, Gutiérrez-Hernandez MA, Sáez-Briones P, Reyes-Parada M, Cassels BK, Clarke WP| title = Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine 5-HT<sub>2A</sub> and 5-HT<sub>2C</sub> receptors| journal = J. Pharmacol. Exp. Ther.| volume = 321| issue = 3| pages = 1054–61| year = 2007| pmid = 17337633| doi = 10.1124/jpet.106.117507 }}</ref><br/>
[[Image:2,5-dma.png|120px]][[Image:2C-N.png|130px]]

Recent research has suggested potential signaling differences within the somatosensory cortex between 5-HT<sub>2A</sub> agonists that produce [[headshake response|headshakes]] in the [[mouse]] and those that do not, such as [[lisuride]], as these agents are also non-hallucinogenic in humans despite being active 5-HT<sub>2A</sub> agonists.<ref name="pmid17270739">{{cite journal| author = González-Maeso J, Weisstaub NV, Zhou M, Chan P, Ivic L, Ang R, Lira A, Bradley-Moore M, Ge Y, Zhou Q, [[Stuart C. Sealfon | Sealfon SC]], Gingrich JA| title = Hallucinogens recruit specific cortical 5-HT<sub>2A</sub> receptor-mediated signaling pathways to affect behavior| journal = Neuron| volume = 53| issue = 3| pages = 439–52| year = 2007| pmid = 17270739| doi = 10.1016/j.neuron.2007.01.008 }}</ref><ref name="pmid18703043">{{cite journal| author = Cussac D, Boutet-Robinet E, Ailhaud MC, Newman-Tancredi A, Martel JC, Danty N, Rauly-Lestienne I| title = Agonist-directed trafficking of signalling at serotonin 5-HT<sub>2A</sub>, 5-HT<sub>2</sub>B and 5-HT<sub>2</sub>C-VSV receptors mediated Gq/11 activation and calcium mobilisation in CHO cells| journal = Eur. J. Pharmacol.| volume = 594| issue = 1-3| pages = 32–8| year = 2008| month = October| pmid = 18703043| doi = 10.1016/j.ejphar.2008.07.040| url =  }}</ref>
The difference in signal transduction between the two 5-HT<sub>2A</sub> agonists serotonin and [[2,5-dimethoxy-4-iodoamphetamine|DOI]] may be due to the presence of the intracellular proteins called β-[[arrestin]]s, more specifically [[arrestin beta 2]].<ref name="pmid18195357">{{cite journal| author = Schmid CL, Raehal KM, Bohn LM| title = Agonist-directed signaling of the serotonin 2A receptor depends on beta-arrestin-2 interactions in vivo| journal = Proc. Natl. Acad. Sci. U.S.A.| volume = 105| issue = 3| pages = 1079–84| year = 2008| pmid = 18195357| doi = 10.1073/pnas.0708862105| pmc = 2242710 }}</ref><ref name="pmid18195368">{{cite journal| author = Abbas A, Roth BL| title = Arresting serotonin| journal = Proc. Natl. Acad. Sci. U.S.A.| volume = 105| issue = 3| pages = 831–2| year = 2008| pmid = 18195368| doi = 10.1073/pnas.0711335105| pmc = 2242676 }}</ref>

=== Role of lipophilicity ===

A set of ligands were evaluated. For agonists, a highly significant linear correlation was observed between [[Dissociation constant#Protein-ligand binding|binding affinity]] and [[lipophilicity]]. For ligands exhibiting partial agonist or antagonist properties, the lipophilicity was consistently higher than would be expected for an agonist of comparable affinity.<ref name="pmid18296055">{{cite journal| author = Parker MA, Kurrasch DM, Nichols DE| title = The role of lipophilicity in determining binding affinity and functional activity for 5-HT<sub>2A</sub> receptor ligands| journal = Bioorg. Med. Chem.| volume = 16| issue =8| pages = 4661–9| year = 2008| pmid = 18296055| doi = 10.1016/j.bmc.2008.02.033| pmc = 2442558 }}</ref>

== Genetics ==
[[Image:Chromosome 13.jpeg|thumb|right|[[Chromosome 13|Chromosome&nbsp;13]].]]
The 5-HT<sub>2A</sub> receptors is coded by the ''HTR2A'' gene.
In humans the gene is located on [[chromosome 13]].
The gene has previously been called just HTR2 until the description of two related genes ''[[HTR2B]]'' and ''[[HTR2C]]''.
Several interesting [[polymorphism (biology)|polymorphism]]s  have been identified for HTR2A: 
[[A-1438G]] ([[rs6311]]), 
[[C102T]] ([[rs6313]]) and 
[[His452Tyr]] ([[rs6314]]).
Many more polymorphisms exist for the gene.
A 2006 paper listed 255.<ref>{{Cite web
| title = OSIRIS search results. Gene: HTR2A
| url = http://bioinformatics.oxfordjournals.org/cgi/content/full/btl421v1/DC1/2
}} Supplementary material to article
*  {{cite journal| author = Chambers JJ, Kurrasch-Orbaugh DM, Parker MA, Nichols DE| title = Enantiospecific synthesis and pharmacological evaluation of a series of super-potent, conformationally restricted 5-HT(2A/2C) receptor agonists| journal = Journal of medicinal chemistry| volume = 44| issue = 6| pages = 1003–10| year = 2001| month = March| pmid = 11300881| doi = 10.1021/jm000491y }}</ref>

=== Associations with psychiatric disorders ===

Several studies have seen links between the -1438G/A polymorphism and [[mood disorders]], such as [[bipolar disorder]]<ref name="pmid11702051">{{Cite journal
| author = Chee IS, Lee SW, Kim JL, Wang SK, Shin YO, Shin SC, Lee YH, Hwang HM, Lim MR
| title = 5-HT<sub>2A</sub> receptor gene promoter polymorphism -1438A/G and bipolar disorder
| journal = Psychiatr. Genet.
| volume = 11
| issue = 3
| pages = 111–114
| year = 2001
| pmid = 11702051
| doi =10.1097/00041444-200109000-00001
 }}</ref>
and [[major depressive disorder]].<ref name="pmid14730199">{{cite journal
| author = Choi MJ, Lee HJ, Lee HJ, Ham BJ, Cha JH, Ryu SH, Lee MS
| title = Association between major depressive disorder and the -1438A/G polymorphism of the serotonin 2A receptor gene
| journal = Neuropsychobiology
| volume = 49
| issue = 1
| pages = 38–41
| year = 2004
| pmid = 14730199
| doi = 10.1159/000075337
}}</ref>
A weak link with an [[odds ratio]] of 1.3 has been found between the T102C polymorphism and [[schizophrenia]].<ref name="pmid8622505">{{cite journal
| author = Williams J, Spurlock G, McGuffin P, Mallet J, Nöthen MM, Gill M, Aschauer H, Nylander PO, Macciardi F, Owen MJ
| title = Association between schizophrenia and T102C polymorphism of the 5-hydroxytryptamine type 2a-receptor gene. European Multicentre Association Study of Schizophrenia (EMASS) Group
| journal = The Lancet
| volume = 347
| issue = 9011
| pages = 1294–1296
| year = 1996
| pmid = 8622505
}}</ref>
This polymorphism has also been studied in relation to [[suicide]] attempts, with a study finding excess of the C/C genotypes among the suicide attempters.<ref name="pmid18163387">{{cite journal| author = Vaquero-Lorenzo C, Baca-Garcia E, Diaz-Hernandez M, Perez-Rodriguez MM, Fernandez-Navarro P, Giner L, Carballo JJ, Saiz-Ruiz J, Fernandez-Piqueras J, Baldomero EB, de Leon J, Oquendo MA| title = Association study of two polymorphisms of the serotonin-2A receptor gene and suicide attempts| journal = American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics| volume = 147B| issue = 5| pages = 645–9| year = 2008| month = July| pmid = 18163387| doi = 10.1002/ajmg.b.30642| url =  }}</ref> A number of other studies were devoted to finding an association of the gene with schizophrenia, with diverging results.<!--

--><ref name="SZgene">[http://www.schizophreniaforum.org/res/sczgene/geneoverview.asp?geneid=293 Gene Overview of All Published Schizophrenia-Association Studies for HTR2A] - [[SzGene]] database at [[Schizophrenia Research Forum]].</ref>

These individual studies may, however, not give a full picture: A review from 2007 looking at the effect of different SNPs reported in separate studies stated that "genetic association studies &#91;of ''HTR2A'' gene variants with psychiatric disorders&#93; report conflicting and generally negative results" with no involvement, small or a not replicated role for the genetic variant of the gene.<ref name="pmid17691947">{{cite journal| author = Serretti A, Drago A, De Ronchi D| title = HTR2A gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies| journal = Current medicinal chemistry| volume = 14| issue = 19| pages = 2053–69| year = 2007| pmid = 17691947| doi = 10.2174/092986707781368450| url = }}</ref>

==== Treatment response ====

One study has found that genetic variations between individuals in the HTR2A gene may to some extent account for the difference in outcome of antidepressant treatment, so that patients suffering from [[major depressive disorder]] and treated with [[Citalopram]] may benefit more than others if they have one particular genotype.<ref name="pmid16642436">{{cite journal
| author = McMahon FJ, Buervenich S, Charney D, Lipsky R, Rush AJ, Wilson AF, Sorant AJ, Papanicolaou GJ, Laje G, Fava M, Trivedi MH, Wisniewski SR, Manji H
| title = Variation in the gene encoding the serotonin 2A receptor is associated with outcome of antidepressant treatment
| journal = Am. J. Hum. Genet.
| volume = 78
| issue = 5
| pages = 804–814
| year = 2006
| pmid = 16642436
| doi = 10.1086/503820
| pmc = 1474035
}}</ref>
In this study 768 [[single nucleotide polymorphism]] (SNP) across 68 genes were investigated and a SNP&mdash;termed [[rs7997012]]&mdash;in the second [[intron]] of the HTR2A gene showed significant association with treatment outcome.

Genetics seems also to be associated to some extent with the amount of adverse events in treatment of major depression disorder.<ref name="pmid17898344">{{cite journal
| author = Laje G, Paddock S, Manji H, Rush AJ, Wilson AF, Charney D, McMahon FJ
| title = Genetic markers of suicidal ideation emerging during citalopram treatment of major depression
| journal = Am J Psychiatry
| volume = 164
| issue = 10
| pages = 1530–1538
| year = 2007
| pmid = 17898344
| doi = 10.1176/appi.ajp.2007.06122018
}}</ref><ref name="pmid17949692">{{cite journal
| author = Laje G, McMahon FJ
| title = The pharmacogenetics of major depression: past, present, and future
| journal = Biol. Psychiatry
| volume = 62
| issue = 11
| pages = 1205–1207
| year = 2007
| pmid = 17949692
| doi = 10.1016/j.biopsych.2007.09.016
}}</ref>

== Neuroimaging ==

The 5-HT<sub>2A</sub> receptors may be imaged with [[PET-scanner]]s using the fluorine-18-[[altanserin]]<ref name="pmid1744713">{{Cite journal
| author = Lemaire C, Cantineau R, Guillaume M, Plenevaux A, Christiaens L
| title = Fluorine-18-altanserin: a radioligand for the study of serotonin receptors with PET: radiolabeling and in vivo biologic behavior in rats
| journal = Journal of Nuclear Medicine
| volume = 32
| issue = 12
| pages = 2266–2272
| date = 1 December 1991 
| pmid = 1744713
| url = http://jnm.snmjournals.org/cgi/content/abstract/32/12/2266
}}</ref>
and MDL&nbsp;100,907<ref name="pmid8602111">{{Cite journal
| author = Lundkvist C, Halldin C, Ginovart N, Nyberg S, Swahn CG, Carr AA, Brunner F, Farde F
| title = <sup>11</sup>C-MDL 100907, a radioligland for selective imaging of 5-HT<sub>2A</sub> receptors with positron emission tomography
| journal = Life Sci.
| volume = 58
| issue = 10
| pages = PL 187–192
| year = 1996
| pmid = 8602111
| doi = 10.1016/0024-3205(96)00013-6
}}</ref>
[[radioligand]]s that binds to the neuroreceptor, e.g., 
one study reported a ''reduced'' binding of altanserin particularly in the [[hippocampus]] in patients with [[major depressive disorder]].<ref name="pmid14744461">{{cite journal
| author = Mintun MA, Sheline YI, Moerlein SM, Vlassenko AG, Huang Y, Snyder AZ
| title = Decreased hippocampal 5-HT<sub>2A</sub> receptor binding in major depressive disorder: in vivo measurement with [<sup>18</sup>F]-altanserin positron emission tomography
| journal = Biological Psychiatry
| volume = 55
| issue = 3
| pages = 217–24
| year = 2004
| pmid = 14744461
| doi = 10.1016/j.biopsych.2003.08.015}}</ref>
Another PET study reported ''increased'' altanserin binding in the [[caudate nucleus|caudate nuclei]] in [[obsessive compulsive disorder]] patients compared to a healthy control group.<ref name="pmid15801987">{{Cite journal 
| author = Adams KH, Hansen ES, Pinborg LH, Hasselbalch SG, Svarer C, Holm S, Bolwig TG, Knudsen GM
| title = Patients with obsessive-compulsive disorder have increased 5-HT<sub>2A</sub> receptor binding in the caudate nuclei
| journal = International  Journal of Neuropsychopharmacology
| volume = 8
| issue = 3
| pages = 391–401
| year = 2005
| pmid = 15801987
| doi = 10.1017/S1461145705005055
}}</ref>

Patients with [[Tourette's syndrome]] have also been scanned and the study found an increased binding of altanserin for patients compared to healthy controls.<ref name="pmid16945163">{{cite journal| author = Haugbøl S, Pinborg LH, Regeur L, Hansen ES, Bolwig TG, Nielsen FA, Svarer C, Skovgaard LT, Knudsen GM| title = Cerebral 5-HT<sub>2A</sub> receptor binding is increased in patients with Tourette's syndrome| journal = Int. J. Neuropsychopharmacol.| volume = 10| issue = 2| pages = 245–52| year = 2007| pmid = 16945163| doi = 10.1017/S1461145706006559 }}</ref> The altanserin uptake decreases with [[aging|age]] reflecting a loss of specific 5-HT<sub>2A</sub> receptors with age.<ref name="pmid9027929">{{cite journal
| author = Rosier A, Dupont P, Peuskens J, Bormans G, Vandenberghe R, Maes M, de Groot T, Schiepers C, Verbruggen A, Mortelmans L
| title = Visualisation of loss of 5-HT<sub>2A</sub> receptors with age in healthy volunteers using [<sup>18</sup>F]-altanserin and positron emission tomographic imaging
| journal = Psychiatry Res.
| volume = 68
| issue = 1
| pages = 11–22
| year = 1996
| pmid = 9027929
| doi = 10.1016/S0925-4927(96)02806-5
}}</ref><ref name="pmid9824691">{{Cite journal
| author = Meltzer CC, Smith G, Price JC, Reynolds CF, Mathis CA, Greer P, Lopresti B, Mintun MA, Pollock BG, Ben-Eliezer D, Cantwell MN, Kaye W, DeKosky ST
| title = Reduced binding of [<sup>18</sup>F]-altanserin to serotonin type 2A receptors in aging: persistence of effect after partial volume correction
| journal = Brain Res.
| volume = 813
| issue = 1
| pages = 167–171
| year = 1998
| pmid = 9824691
| doi = 10.1016/S0006-8993(98)00909-3
}}</ref><ref name="pmid15006678">{{Cite journal
| author = Adams KH, Pinborg LH, Svarer C, Hasselbalch SG, Holm S, Haugbøl S, Madsen K, Frøkjaer V, Martiny L, [[Olaf B. Paulson]], Knudsen GM
| title = A database of [<sup>18</sup>F]-altanserin binding to 5-HT<sub>2A</sub> receptors in normal volunteers: normative data and relationship to physiological and demographic variables
| journal = NeuroImage
| volume = 21
| issue = 3
| pages = 1105–1113
| year = 2004
| pmid = 15006678
| doi = 10.1016/j.neuroimage.2003.10.046
}}</ref>
A study has also found a positive correlation among healthy subjects between altanserin binding and the personality trait [[neuroticism]] as measured by the [[NEO PI-R]] personality questionnaire.<ref name="pmid17884017">{{Cite journal
| author = Frøkjær VG, Mortensen EL, Nielsen FÅ, Haugbøl S, Pinborg LH, Adams KH, Svarer C, Hasselbalch SG, Holm S, [[Olaf B. Paulson|Paulson OB]], Knudsen GM
| title = Frontolimbic serotonin 2A receptor binding in healthy subjects is associated with personality risk factors for affective disorder| journal = Biological Psychiatry
| volume = 63
| issue = 6
| pages = 569–76
| year = 2008
| pmid = 17884017
| doi = 10.1016/j.biopsych.2007.07.009
}}</ref>

== Role In virus endocytosis ==

5-HT<sub>2A</sub> is a necessary receptor for [[clathrin]] mediated [[endocytosis]] of the human [[polyoma virus]] called [[JC virus]], the causative agent of [[progressive multifocal leukoencephalopathy]] (PML), that enters cells like [[oligodendrocyte]]s, [[astrocyte]]s, [[B lymphocytes]], and kidney epithelial cells. These cells need to express both the alpha 2-6–linked [[sialic acid]] component of the 5HT<sub>2A</sub> receptor in order to endocytose JCV.<ref name="pmid15550673"/>

==References==
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{{Reflist|2}}

==External links==
* {{cite web| url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2320| title = 5-HT<sub>2A</sub>| accessdate =| authorlink =| coauthors =| date =| format =| work = IUPHAR Database of Receptors and Ion Channels| publisher = International Union of Basic and Clinical Pharmacology| pages =| language =| archiveurl =| archivedate =| quote = }}

* {{MeshName|5-HT2A+Receptor}}

{{G protein-coupled receptors}}
{{Cell signaling}}
{{Serotonergics}}

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{{DEFAULTSORT:5-Ht2a Receptor}}
[[Category:Signal transduction]]
[[Category:G protein coupled receptors]]
[[Category:Biology of bipolar disorder]]

[[ru:5-HT2A-рецептор]]
[[Category:2Fix]]