5-HT2A-рецептор: различия между версиями

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{{DISPLAYTITLE:5-HT<sub>2A</sub>-рецептор}}
{{DISPLAYTITLE:5-HT<sub>2A</sub>-рецептор}}
{{PBB|geneid=3356}}
{{белок
|name=5-hydroxytryptamine (serotonin) receptor 2A
|caption=
|image=
|width=
|HGNCid=5293
|Symbol=HTR2A
|AltSymbols=HTR2
|EntrezGene=3356
|OMIM=182135
|RefSeq=NM_000621
|UniProt=P28223
|PDB=
|ECnumber=
|Chromosome=13
|Arm=q
|Band=14-21
|LocusSupplementaryData=
}}
'''5-HT<sub>2A</sub>-рецептор''' - один из [[серотониновый рецептор|серотониновых рецепторов]], входящих в семейство [[5-HT2]]. Кодируется геном HTR2A на [[13-я хромосома человека|13-й хромосоме]]. Он является основным возбудительным [[GPCR|G-белок-сопряжённым]] рецептором [[серотонин]]а, однако способен оказывать и ингибирующее воздействие в таких областях, как [[зрительная кора]] и [[орбитофронтальная кора]].


<!---
Ряд исследований связывает ген HTR2 с [[шизофрения|шизофренией]],<!--


The mammalian '''5-HT<sub>2A</sub> receptor''' is a subtype of the [[5-HT2 receptor|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 = 465–469 | date = August 1994 | 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<ref>{{cite journal | author = Martin P, Waters N, Schmidt CJ, Carlsson A, Carlsson ML | title = Rodent data and general hypothesis: antipsychotic action exerted through 5-HT2A receptor antagonism is dependent on increased serotonergic tone | journal = J Neural Transm | volume = 105 | issue = 4–5 | pages = 365–396 | year = 1998 | pmid = 9720968 | doi = 10.1007/s007020050064 }}</ref> on certain areas such as the [[visual cortex]] and the [[orbitofrontal cortex]]. This receptor was first given importance as the target of [[Psychedelic drugs#Serotonergic or classical psychedelics .285-HT2A receptor agonists.29|serotonergic psychedelic drugs]] such as [[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.
--><ref name="SzGene">{{cite web|url=http://www.schizophreniaforum.org/res/sczgene/geneoverview.asp?geneid=293|title=Gene Overview of All Published Schizophrenia-Association Studies for HTR2A|work=база данных [[SZgene]],|publisher=[[Schizophrenia Research Forum]]|archiveurl=http://www.webcitation.org/68FyLFlin|archivedate=2012-06-08}}</ref><!--


5-HT<sub>2A</sub> may 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>
--> однако результаты противоречивы и обзоры говорят о том, что связь гена с расстройствами психики отсутствует либо очень мала.<!--


Downregulation of post-synaptic 5-HT<sub>2A</sub> receptor is an adaptive process provoked by chronic administration of SSRIs and classical antipsychotics. Deceased suicidal and otherwise depressed patients have had more 5-HT<sub>2A</sub> receptors than normal patients. These findings suggest that post-synaptic 5-HT<sub>2A</sub> overdensity is involved in the pathogenesis of depression.<ref name=pmid8788498>{{cite journal | author = Eison AS, Mullins UL | title = Regulation of central 5-HT2A receptors: a review of in vivo studies | journal = Behavioural Brain Research | volume = 73 | issue = 1–2 | pages = 177–81 | year = 1996 | pmid = 8788498 | doi = 10.1016/0166-4328(96)00092-7 }}</ref>
--><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 = | url = http://www.bentham-direct.org/pages/content.php?CMC/2007/00000014/00000019/0005C.SGM | issn = }}</ref><!--


== История ==
--> Вариации гена HTR2A, по данным некоторых исследований, оказывают влияние, пусть и небольшое, на показатели [[преимпульсное ингибирование|преимпульсного ингибирования]] - предположительной [[эндофенотип]]ной черты шизофрении, и тем самым, возможно, могут немного усиливать либо ослаблять риск заболевания.<!--


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 receptor]]s 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.<ref>{{cite book |title=Basic neurochemistry: molecular, cellular, and medical aspects |volume=1 |author=George J. Siegel, R. Wayne Albers |edition=7th ed |isbn=0-12-088397-X |publisher=Academic Press |year=2005 |url=http://books.google.com/books?id=Af0IyHtGCMUC&pg=PA241&lpg=PA241&dq=5-HT1,+5-HT2++5-HT3+receptors+LSD,+spiperone+morphine&source=bl&ots=zm70d7W4RD&sig=AvK5yZ9P1CuoRE3ac4-BGV1LjXo&hl=en&ei=VuklTv7zEqHg0QH5zJjUCg&sa=X&oi=book_result&ct=result&resnum=1&ved=0CBoQ6AEwAA#v=onepage&q=5-HT1%2C%205-HT2%20%205-HT3%20receptors%20LSD%2C%20spiperone%20morphine&f=false |pages=241}}</ref> 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> (formerly known as 5-HT<sub>2</sub> or D), the [[5-HT2B receptor|5-HT<sub>2B</sub>]] (formerly known as 5-HT<sub>2F</sub>) and the [[5-HT2C|5-HT<sub>2C</sub>]] (formerly known as 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 | date = April 2002 | pmid = 11888546 | doi = 10.1016/S0091-3057(01)00746-8 | url = | issn = }}</ref>
--><ref name="pmid18985293">{{cite journal |author=Maier W, Mössner R, Quednow BB, Wagner M, Hurlemann R |title=From genes to psychoses and back: the role of the 5HT2alpha-receptor and prepulse inhibition in schizophrenia |journal=[[Eur Arch Psychiatry Clin Neurosci]] |volume=258 Suppl 5 |issue= |pages=40–3 |year=2008 |month=November |pmid=18985293 |doi=10.1007/s00406-008-5011-5 |url=http://dx.doi.org/10.1007/s00406-008-5011-5}}</ref>


== Распределение ==
Существуют свидетельства того, что 5-HT<sub>2A</sub> образует комплекс с [[метаботропный глутаматный рецептор|метаботропным глутаматным рецептором]] [[mGluR2|mGluR<sub>2</sub>]].<!--


5-HT<sub>2A</sub> is expressed widely throughout the [[central nervous system]] (CNS).
--><ref name="pmid18297054">{{cite journal |author=González-Maeso J, Ang RL, Yuen T, Chan P, Weisstaub NV, López-Giménez JF, Zhou M, Okawa Y, Callado LF, Milligan G, Gingrich JA, Filizola M, Meana JJ, Sealfon SC |title=Identification of a serotonin/glutamate receptor complex implicated in psychosis |journal=[[Nature]] |volume=452 |issue=7183 |pages=93–7 |year=2008 |month=March |pmid=18297054 |doi=10.1038/nature06612 |url=http://dx.doi.org/10.1038/nature06612}}</ref><!--
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, working memory, and attention<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 | date = April 1999 | 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 | date = December 2005 | 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 | date = March 2004 | 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 = 6502–6511 | date = September 2001 | 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 | date = March 2009 | pmid = 19324062 | pmc = 2706691 | doi = 10.1016/j.neuropharm.2009.03.005 | url = | issn = }}</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 | date = January 2008 | 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 | volume = 23 | issue = 5 | pages = 569–76 | date = November 2000 | 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 | date = September 2008 | pmid = 18621097 | pmc = 2677702 | doi = 10.1016/j.neulet.2008.06.083 | url = | issn = }}</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 | date = November 2007 | pmid = 17656637 | pmc = 2779889 | doi = 10.1093/schbul/sbm088 | url = | issn = }}</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 = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 1 | pages = 359–64 | date = January 2008 | 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 (cerebral cortex)|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 | date = June 2002 | 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 = 72–74 | date = August 1998 | 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 = 411–417 | date = December 2004 | 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. Additionally, 5-HT<sub>2A</sub> mRNA expression has been observed in human [[monocytes]].<ref name="pmid15802305">{{cite journal | author = Dürk T, Panther E, Müller T, Sorichter S, Ferrari D, Pizzirani C, Di Virgilio F, Myrtek D, Norgauer J, Idzko M | title = 5-Hydroxytryptamine modulates cytokine and chemokine production in LPS-primed human monocytes via stimulation of different 5-HTR subtypes | journal = Int Immunol | volume = 17 | issue = 5 | pages = 599–606 | date = May 2005 | pmid = 15802305 | doi = 10.1093/intimm/dxh242 | url = | issn = }}</ref>
--> Возможно, этот комплекс опосредует [[психоз|психотическое]] воздействие [[галлюциноген]]ов.<!--


== Сигнальный каскад ==
--><ref name="SRF1">{{cite web|url=http://www.schizophreniaforum.org/new/detail.asp?id=1423|title=5HT and Glutamate Receptors—Unique Complex Linked to Psychosis|publisher=[[Форум исследования шизофрении]]|work=обзор публикаций|date=март 2008 г.|archiveurl=http://www.webcitation.org/68FyLxbtW|archivedate=2012-06-08}} Перевод: {{cite web|url=http://forum.neuroscience.ru/blog.php?b=26|title=Уникальный комплекс рецепторов 5HT2A и mGluR2, связанный с механизмами психоза|deadlink=unknown-host}}</ref>


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]] (DAG) and [[inositol triphosphate]] (IP3), which in turn stimulate [[protein kinase C]] (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>
В одном исследовании [[психоделик]] [[2,5-диметокси-4-иодамфетамин|DOI]] - специфический агонист рецептора 5-HT<sub>2A</sub> - вызвал временное увеличение [[дендритный шипик|дендритных шипиков]], как предполагают авторы, через механизмы, связанные с [[калирин|калирином-7]].<!--


There are many additional signal cascade components that include the formation of [[arachidonic acid]] through [[PLA2]] activity, activation of [[phospholipase D]], [[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}}
--><ref name="pmid19889983">{{cite journal |author=Jones KA, Srivastava DP, Allen JA, Strachan RT, Roth BL, Penzes P |title=Rapid modulation of spine morphology by the 5-HT2A serotonin receptor through kalirin-7 signaling |journal=[[Proc. Natl. Acad. Sci. U.S.A.]] |volume= |issue= |pages= |year=2009 |month=November |pmid=19889983 |doi=10.1073/pnas.0905884106 |url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=19889983}}</ref>


== Физиологические эффекты ==
==Клиническое значение==
В одном [[Позитронно-эмиссионная томография|PET]]-исследовании 30 пациентов с диагнозом [[шизофрения|шизофрении]], переживших первый [[психоз]], но ещё не получавших [[антипсихотик]]ов, отмечено сниженное связывание радиолиганда (меченый [[:en:Altanserin|алтансерин]]) к рецептору в префронтальной коре мозга.<!--


Physiological processes mediated by the receptor include:
--><ref name="pmid20048218">Научная публикация, обзор на тематическом портале:
* CNS: neuronal excitation, behavioural effects, learning, anxiety
*{{cite journal |author=Rasmussen H, Erritzoe D, Andersen R, Ebdrup BH, Aggernaes B, Oranje B, Kalbitzer J, Madsen J, Pinborg LH, Baaré W, Svarer C, Lublin H, Knudsen GM, Glenthoj B |title=Decreased frontal serotonin2A receptor binding in antipsychotic-naive patients with first-episode schizophrenia |journal=[[Arch. Gen. Psychiatry]] |volume=67 |issue=1 |pages=9–16 |year=2010 |month=January |pmid=20048218 |doi=10.1001/archgenpsychiatry.2009.176 |url=http://archpsyc.ama-assn.org/cgi/pmidlookup?view=long&pmid=20048218}}
* smooth muscle: contraction (in [[gastrointestinal tract]] & [[bronchi]])
*{{cite web|url=http://www.schizophreniaforum.org/new/detail.asp?id=1567|title=Serotonin Receptors Appear Reduced in First-Episode Schizophrenia|quote=сообщается о снижении серотониновых рецепторов при первом эпизоде шизофрении|publisher=сайт [[Форум исследования шизофрении]]|author=Michele Solis|date=16 января 2010|archiveurl=http://www.webcitation.org/68FyMVWw7|archivedate=2012-06-08}}</ref><!--
* [[vasoconstriction]] / [[vasodilation]]
* platelets: [[platelet aggregation|aggregation]]
* Activation of the 5-HT<sub>2A</sub> receptor with DOI produces potent [[anti-inflammatory]] effects in several tissues including cardiovascular and gut. 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 = 316–323 | date = November 2008 | pmid = 18708586 | doi = 10.1124/jpet.108.143461 | url = }}</ref><ref>{{cite journal | author = Nau F, Yu B, Martin D, Nichols CD | title = Serotonin 5-HT2A Receptor Activation Blocks TNF-a Mediated Inflammation In Vivo | journal = PLOS One | volume = 8 | issue = 10 | pages = e75426 | year = 2013 | pmid = 24098382 | doi = 10.1371/journal.pone.0075426 | url = }}</ref>
* Activation of the 5-HT<sub>2A</sub> receptor in hypothalamus causes increases in hormonal levels of [[oxytocin]], [[prolactin]], [[ACTH]], [[corticosterone]], and [[renin]].<ref>{{cite journal | author = Van de Kar LD, Javed A, Zhang Y, Serres F, Raap DK, Gray TS | title = 5-HT2A receptors stimulate ACTH, corticosterone, oxytocin, renin, and prolactin release and activate hypothalamic CRF and oxytocin-expressing cells | journal = The Journal of neuroscience : the official journal of the Society for Neuroscience | volume = 21 | issue = 10 | pages = 3572–3579 | year = 2001 | pmid = 11331386 }}</ref><ref>{{cite journal | author = Zhang Y, Damjanoska KJ, Carrasco GA, Dudas B, D'Souza DN, Tetzlaff J, Garcia F, Hanley NR, Scripathirathan K, Petersen BR, Gray TS, Battaglia G, Muma NA, Van de Kar LD | title = Evidence that 5-HT2A receptors in the hypothalamic paraventricular nucleus mediate neuroendocrine responses to (-)DOI | journal = J Neurosci. | volume = 22 | issue = 21 | pages = 9635–9642 | date = November 2002 | pmid = 12417689 | doi = }}</ref>
* Role in memory<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 | pmid = 16277612 | doi = 10.1111/j.1471-4159.2005.03485.x }}</ref><ref name="pmid14557608">{{cite journal | author = Harvey JA | title = Role of the serotonin 5-HT(2A) receptor in learning | journal = Learn. Mem. | volume = 10 | issue = 5 | pages = 355–62 | year = 2003 | pmid = 14557608 | pmc = 218001 | doi = 10.1101/lm.60803 }}</ref><ref name="pmid11923449">{{cite journal | author = Williams GV, Rao SG, Goldman-Rakic PS | title = The physiological role of 5-HT2A receptors in working memory | journal = J. Neurosci. | volume = 22 | issue = 7 | pages = 2843–54 | year = 2002 | pmid = 11923449}}</ref>


== Ligands ==
--> Как сообщают авторы этого небольшого исследования, чем ниже было число обнаруженных рецепторов у пациентов-мужчин, тем меньше отмечалось психотических симптомов; аналогичной корреляции уровня рецептора с показателями [[рабочая память|рабочей памяти]], внимания, и со способностями к решению задач не отмечено.


=== Агонисты ===
{{neuroscience-stub}}
{{biology-stub}}


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>{{cite journal | author = Nichols DE | title = Hallucinogens. | journal = Pharmacology & therapeutics | volume = 101 | issue = 2 | pages = 131–181 | year = 2004 | pmid = 14761703 | doi = 10.1016/j.pharmthera.2003.11.002 }}</ref><ref name="pmid18666267">{{cite journal | author = Blaazer AR, Smid P, Kruse CG | title = Structure-activity relationships of phenylalkylamines as agonist ligands for 5-HT(2A) receptors | journal = ChemMedChem | volume = 3 | issue = 9 | pages = 1299–309 | year = 2008 | pmid = 18666267 | doi = 10.1002/cmdc.200800133 }}</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. Newer findings reveal that psychoactive effects of classic psychedelics are mediated by the [[GPCR oligomer|receptor heterodimer]] 5-HT<sub>2A</sub>-[[Metabotropic glutamate receptor 2|mGlu2]] and not by [[monomer]]ic 5-HT<sub>2A</sub> receptors.<ref>{{cite journal | author = Moreno JL, Muguruza C, Umali A, Mortillo S, Holloway T, Pilar-Cuéllar F, Mocci G, Seto J, Callado LF, Neve RL, Milligan G, Sealfon SC, López-Giménez JF, Meana JJ, Benson DL, González-Maeso J | title = Identification of Three Residues Essential for 5-Hydroxytryptamine 2A-Metabotropic Glutamate 2 (5-HT2A{middle dot}mGlu2) Receptor Heteromerization and Its Psychoactive Behavioral Function | journal = Journal of Biological Chemistry | volume = 287 | issue = 53 | pages = 44301–44319 | year = 2012 | pmid = 23129762 | pmc = 3531745 | doi = 10.1074/jbc.M112.413161 }}</ref><ref>{{cite journal | author = González-Maeso J, Ang RL, Yuen T, Chan P, Weisstaub NV, López-Giménez JF, Zhou M, Okawa Y, Callado LF, Milligan G, Gingrich JA, Filizola M, Meana JJ, Sealfon SC | title = Identification of a serotonin/glutamate receptor complex implicated in psychosis | journal = Nature | volume = 452 | issue = 7183 | pages = 93–97 | year = 2008 | pmid = 18297054 | pmc = 2743172 | doi = 10.1038/nature06612 }}</ref><ref>{{cite journal | author = Moreno JL, Holloway T, Albizu L, Sealfon SC, González-Maeso J | title = Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists | journal = Neuroscience Letters | volume = 493 | issue = 3 | pages = 76–79 | year = 2011 | pmid = 21276828 | pmc = 3064746 | doi = 10.1016/j.neulet.2011.01.046 }}</ref> Agonists enhance dopamine in PFC,<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 | pmid = 16277612 | doi = 10.1111/j.1471-4159.2005.03485.x }}</ref> enhances memory and plays a role in attention and learning.<ref name="pmid17124621">{{cite journal | author = Wingen M, Kuypers KP, Ramaekers JG | title = The role of 5-HT1a and 5-HT2a receptors in attention and motor control: a mechanistic study in healthy volunteers | journal = Psychopharmacology (Berl.) | volume = 190 | issue = 3 | pages = 391–400 | year = 2007 | pmid = 17124621 | doi = 10.1007/s00213-006-0614-x }}</ref><ref name="pmid17092965">{{cite journal | author = Wingen M, Kuypers KP, Ramaekers JG | title = Selective verbal and spatial memory impairment after 5-HT1A and 5-HT2A receptor blockade in healthy volunteers pre-treated with an SSRI | journal = J. Psychopharmacol. (Oxford) | volume = 21 | issue = 5 | pages = 477–85 | year = 2007 | pmid = 17092965 | doi = 10.1177/0269881106072506 }}</ref>
==Примечания==

{{reflist|2}}
==== Полные агонисты ====

* [[25I-NBOH]] and its 2-methoxy-analog [[25I-NBOMe]]<ref name="pmid17000863">{{cite journal | author = Braden MR, Parrish JC, Naylor JC, 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 = 1956–1964 | year = 2006 | pmid = 17000863 | doi = 10.1124/mol.106.028720 }}</ref>
* [[2,5-Dimethoxy-4-iodoamphetamine|(R)-DOI]]
* [[TCB-2]]<ref name="pmid16970404">{{cite journal | author = McLean TH, Parrish JC, Braden MR, Marona-Lewicka D, Gallardo-Godoy A, Nichols DE | title = 1-Aminomethylbenzocycloalkanes: conformationally restricted hallucinogenic phenethylamine analogues as functionally selective 5-HT<sub>2A</sub> receptor agonists | journal = Journal of Medical Chemistry | volume = 49 | issue = 19 | pages = 5794–803 | date = September 2006 | pmid = 16970404 | doi = 10.1021/jm060656o | url = }}</ref>
* [[Bromo-DragonFLY]]<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 | date = March 2001 | pmid = 11300881 | doi = 10.1021/jm000491y | url = }}</ref>
* [[Mexamine]] is a full agonist to several serotonin receptors.
* [[O-4310]], 5-HT<sub>2A</sub> selective, claimed to have 100x selectivity over 5-HT<sub>2C</sub> and be inactive at 5-HT<sub>2B</sub>
* [[PHA-57378]], dual 5-HT<sub>2A</sub> / 5-HT<sub>2C</sub> agonist, anxiolytic effects in animal studies.<ref name="pmid12824036">{{cite journal | author = Ennis MD, Hoffman RL, Ghazal NB, Olson RM, Knauer CS, Chio CL, Hyslop DK, Campbell JE, Fitzgerald LW, Nichols NF, Svensson KA, McCall RB, Haber CL, Kagey ML, Dinh DM | title = 2,3,4,5-tetrahydro- and 2,3,4,5,11,11a-hexahydro-1H-[1,4]diazepino[1,7-a]indoles: new templates for 5-HT(2C) agonists | journal = Bioorg. Med. Chem. Lett. | volume = 13 | issue = 14 | pages = 2369–72 |date=July 2003 | pmid = 12824036 | doi = 10.1016/S0960-894X(03)00403-7 }}</ref>

==== Парциальные (частичные) агонисты ====

* [[25C-NBOMe]]
* [[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.
* [[OSU-6162]] acts as a partial agonist at both 5-HT<sub>2A</sub> and [[dopamine D2 receptor|dopamine D<sub>2</sub> receptors]]
* [[25CN-NBOH]], 100x selectivity for 5-HT<sub>2A</sub> over 5-HT<sub>2C</sub>, 46x selectivity over 5-HT<sub>2B</sub>.<ref>[https://docs.google.com/open?id=0BwXelgjm5BeEaEJJU0lPa1NnaGM Martin Hansen PhD. Design and Synthesis of Selective Serotonin Receptor Agonists for Positron Emission Tomography Imaging of the Brain. University of Copenhagen, 2011.]</ref>
* [[Juncosamine]], is a structurally constrained derivative of [[25B-NBOMe]], which acts as a potent partial agonist with 124x selectivity for 5-HT<sub>2A</sub> over 5-HT<sub>2C</sub>, making it the most selective agonist ligand identified to date.<ref>{{cite journal | author = Juncosa JI, Hansen M, Bonner LA, Cueva JP, Maglathlin R, McCorvy JD, Marona-Lewicka D, Lill MA, Nichols DE | title = Extensive rigid analogue design maps the binding conformation of potent N-benzylphenethylamine 5-HT2A serotonin receptor agonist ligands | journal = ACS Chemical Neuroscience | volume = 4 | pages = 120717095020003 | year = 2012 | pmid = | pmc = | doi = 10.1021/cn3000668 }}</ref>
* [[Cannabidiol]], a phytocannabinoid in [[Cannabis]].<ref>{{cite journal | author = Russo EB, Burnett A, Hall B, Parker KK | title = Agonistic Properties of Cannabidiol at 5-HT1a Receptors | journal = Neurochemical Research | volume = 30 | issue = 8 | pages = 1037–1043 | year = 2005 | pmid = 16258853 | pmc = | doi = 10.1007/s11064-005-6978-1 }}</ref>
* [[Efavirenz]], an antiretroviral drug, produces psychiatric side effects thought to be mediated by 5-HT<sub>2A</sub>.<ref>{{cite journal | author = Gatch MB, Kozlenkov A, Huang RQ, Yang W, Nguyen JD, González-Maeso J, Rice KC, France CP, Dillon GH, Forster MJ, Schetz JA | title = The HIV Antiretroviral Drug Efavirenz has LSD-Like Properties | journal = Neuropsychopharmacology | year = 2013 | pmid = 23702798 | pmc = | doi = 10.1038/npp.2013.135 | volume=38 | issue=12 | pages=2373–84}}</ref>
* [[Mefloquine]], an antimalarial drug, also produces psychiatric side effects which may be mediated through 5-HT<sub>2A</sub> and/or 5-HT<sub>2C</sub> receptors.<ref>{{cite journal | author = Janowsky A, Eshleman AJ, Johnson RA, Wolfrum KM, Hinrichs DJ, Yang J, Zabriskie TM, Smilkstein MJ, Riscoe MK | title = Mefloquine and psychotomimetics share neurotransmitter receptor and transporter interactions in vitro | journal = Psychopharmacology | year = 2014 | pmid = 24488404 | doi = 10.1007/s00213-014-3446-0 | volume=231 | issue=14 | pages=2771–83}}</ref>
* [[Lisuride]], an antiparkinson [[dopamine agonist]] of the [[ergoline]] class, that is also a dual 5-HT<sub>2A</sub> / 5-HT<sub>2C</sub> agonist<ref name="pmid9600588">{{cite journal | author = Egan CT, Herrick-Davis K, Miller K, Glennon RA, Teitler M | title = Agonist activity of LSD and lisuride at cloned 5HT2A and 5HT2C receptors | journal = Psychopharmacology (Berl.) | volume = 136 | issue = 4 | pages = 409–14 | date = April 1998 | pmid = 9600588 | doi = 10.1007/s002130050585 | url = }}</ref> and 5-HT<sub>2B</sub> antagonist.<ref name="pmid16614540">{{cite journal | author = Hofmann C, Penner U, Dorow R, Pertz HH, Jähnichen S, Horowski R, Latté KP, Palla D, Schurad B | title = Lisuride, a dopamine receptor agonist with 5-HT2B receptor antagonist properties: absence of cardiac valvulopathy adverse drug reaction reports supports the concept of a crucial role for 5-HT2B receptor agonism in cardiac valvular fibrosis | journal = Clin Neuropharmacol | volume = 29 | issue = 2 | pages = 80–6 | year = 2006 | pmid = 16614540 | doi = 10.1097/00002826-200603000-00005 | url = http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?an=00002826-200603000-00005 }}</ref>

==== Периферические селективные агонисты ====

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 | volume = 23 | issue = 1 | pages = 1–13 | date = February 2007 | 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 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 = 318–328 | date = January 2006 | pmid = 16392816 | doi = 10.1021/jm050663x | url = }}</ref>

=== «Молчаливые» антагонисты ===

* 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.
* The 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]] and [[asenapine]] 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>
* [[LY-367,265]] — dual 5-HT<sub>2A</sub> antagonist / SSRI with antidepressant effects
* 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 | date = March 2008 | 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 | date = September 1999 | 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 | date = June 2002 | 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 | date = December 2003 | 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 | date = November 2008 | pmid = 18847250 | pmc = 3088499 | 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 | date = May 2007 | pmid = 17314044 | doi = 10.1016/j.bmcl.2007.01.098 | url = }}</ref>
* [[Hydroxyzine]] (Atarax)
* [[5-MeO-NBpBrT]]

=== Обратные агонисты ===

* [[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 | date = October 2001 | 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 | date = September 2004 | pmid = 15102927 | doi = 10.1124/jpet.104.066688 | url = }}</ref>
* [[Nelotanserin]] (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>{{cite journal | author = Rosenberg R, Seiden DJ, Hull SG, Erman M, Schwartz H, Anderson C, Prosser W, Shanahan W, Sanchez M, Chuang E, Roth T | title = APD125, a selective serotonin 5-HT<sub>2A</sub> receptor inverse agonist, significantly improves sleep maintenance in primary insomnia | journal = Sleep | volume = 31 | issue = 12 | pages = 1663–71 | year = 2008 | pmid = 19090322 | pmc = 2603489 }}</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.
* [[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 | date = May 2006 | 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 | date = August 2007 | 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 | date = October 2008 | pmid = 18534670 | pmc = 2806670 | doi = 10.1016/j.pbb.2008.04.010 | url = }}</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 | date = December 2008 | pmid = 19040345 | doi = 10.1517/14656560802532707 | url = }}</ref>
* [[Volinanserin]]

=== Функциональная селективность ===

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 />
[[Файл:2,5-dma.png|120px]]
[[Файл: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, 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 | date = October 2008 | pmid = 18703043 | doi = 10.1016/j.ejphar.2008.07.040 | url = }}</ref>
One known example of differences in signal transduction is between the two 5-HT<sub>2A</sub> agonists serotonin and [[2,5-dimethoxy-4-iodoamphetamine|DOI]] that involves differential recruitment of 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 = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 3 | pages = 1079–84 | year = 2008 | pmid = 18195357 | pmc = 2242710 | doi = 10.1073/pnas.0708862105 }}</ref><ref name="pmid18195368">{{cite journal | author = Abbas A, Roth BL | title = Arresting serotonin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 3 | pages = 831–2 | year = 2008 | pmid = 18195368 | pmc = 2242676 | doi = 10.1073/pnas.0711335105 }}</ref>

=== Роль липофильности ===

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 | pmc = 2442558 | doi = 10.1016/j.bmc.2008.02.033 }}</ref>

== Генетика ==

[[Файл:Chromosome 13.jpeg|thumb|right|[[Chromosome 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)|polymorphisms]] 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 Medical Chemistry | volume = 44 | issue = 6 | pages = 1003–10 | date = March 2001 | pmid = 11300881 | doi = 10.1021/jm000491y }}</ref>

=== Ассоциация с психическими заболеваниями ===

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 | doi = 10.1016/s0140-6736(96)90939-3 }}</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 | volume = 147B | issue = 5 | pages = 645–9 | date = July 2008 | 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 | pmc = 1474035 | doi = 10.1086/503820 }}</ref>
In this study 768 [[single nucleotide polymorphism]] (SNP) across 68 genes were investigated and a SNP—termed [[rs7997012]]—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>

One study has also linked abnormal 5-HT<sub>2A</sub> polymorphisms which may enhance receptor activity with [[Chronic Fatigue Syndrome]].<ref>{{cite journal | author = Smith AK, Dimulescu I, Falkenberg VR, Narasimhan S, Heim C, Vernon SD, Rajeevan MS | title = Genetic evaluation of the serotonergic system in chronic fatigue syndrome | journal = Psychoneuroendocrinology | volume = 33 | issue = 2 | pages = 188–197 | year = 2008 | pmid = 18079067 | pmc = | doi = 10.1016/j.psyneuen.2007.11.001 }}</ref>

== Нейровизуализационные исследования ==

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 100,907<ref name="pmid8602111">{{cite journal | author = Lundkvist C, Halldin C, Ginovart N, Nyberg S, Swahn CG, Carr AA, Brunner F, Farde L | 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, Paulson OB, 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 = Frokjaer VG, Mortensen EL, Nielsen FA, Haugbol S, Pinborg LH, Adams KH, Svarer C, Hasselbalch SG, Holm S, 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>

== Роль в эндоцитозе вируса прогрессирующей мультифокальной лейкоэнцефалопатии ==

5-HT<sub>2A</sub> may be 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 such as [[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 5-HT<sub>2A</sub> receptor in order to endocytose JCV.<ref name="pmid15550673"/>

--->

== Примечания ==

{{примечания}}

== Для дополнительного чтения ==

* {{cite journal |author=Perez-Aguilar JM, Shan J, LeVine MV, Khelashvili G, Weinstein H |title=A functional selectivity mechanism at the serotonin-2A GPCR involves ligand-dependent conformations of intracellular loop 2 |journal=J. Am. Chem. Soc. |volume= |issue= |pages= |year=2014 |pmid=25314362 |doi=10.1021/ja508394x |url=}}

== Ссылки ==

* {{cite web| url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2320| title = 5-HT<sub>2A</sub>| accessdate =| authorlink =| 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}}


[[Категория:Серотониновые рецепторы]]
[[Категория:Серотониновые рецепторы]]

Версия от 19:28, 25 января 2015

Шаблон:PBB

[1]

Recent research has suggested potential signaling differences within the somatosensory cortex between 5-HT2A agonists that produce 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-HT2A agonists.[2][3] One known example of differences in signal transduction is between the two 5-HT2A agonists serotonin and DOI that involves differential recruitment of intracellular proteins called β-arrestins, more specifically arrestin beta 2.[4][5]

Роль липофильности

A set of ligands were evaluated. For agonists, a highly significant linear correlation was observed between 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.[6]

Генетика

Chromosome 13.

The 5-HT2A 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 polymorphisms 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.[7]

Ассоциация с психическими заболеваниями

Several studies have seen links between the −1438G/A polymorphism and mood disorders, such as bipolar disorder[8] and major depressive disorder.[9] A weak link with an odds ratio of 1.3 has been found between the T102C polymorphism and schizophrenia.[10] 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.[11] A number of other studies were devoted to finding an association of the gene with schizophrenia, with diverging results.[12]

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 [of HTR2A gene variants with psychiatric disorders] report conflicting and generally negative results» with no involvement, small or a not replicated role for the genetic variant of the gene.[13]

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.[14] In this study 768 single nucleotide polymorphism (SNP) across 68 genes were investigated and a SNP—termed rs7997012—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.[15][16]

One study has also linked abnormal 5-HT2A polymorphisms which may enhance receptor activity with Chronic Fatigue Syndrome.[17]

Нейровизуализационные исследования

The 5-HT2A receptors may be imaged with PET-scanners using the fluorine-18-altanserin[18] and MDL 100,907[19] radioligands 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.[20] Another PET study reported increased altanserin binding in the caudate nuclei in obsessive compulsive disorder patients compared to a healthy control group.[21]

Patients with Tourette's syndrome have also been scanned and the study found an increased binding of altanserin for patients compared to healthy controls.[22] The altanserin uptake decreases with age reflecting a loss of specific 5-HT2A receptors with age.[23][24][25] 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.[26]

Роль в эндоцитозе вируса прогрессирующей мультифокальной лейкоэнцефалопатии

5-HT2A may be 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 such as oligodendrocytes, astrocytes, B lymphocytes, and kidney epithelial cells. These cells need to express both the alpha 2-6-linked sialic acid component of the 5-HT2A receptor in order to endocytose JCV.[27]

--->

Примечания

  1. ↑ Moya PR, Berg KA, Gutiérrez-Hernandez MA, Sáez-Briones P, Reyes-Parada M, Cassels BK, Clarke WP (2007). "Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine 5-HT2A and 5-HT2C receptors". J. Pharmacol. Exp. Ther. 321 (3): 1054—61. doi:10.1124/jpet.106.117507. PMID 17337633.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)
  2. ↑ González-Maeso J, Weisstaub NV, Zhou M, Chan P, Ivic L, Ang R, Lira A, Bradley-Moore M, Ge Y, Zhou Q, Sealfon SC, Gingrich JA (2007). "Hallucinogens recruit specific cortical 5-HT2A receptor-mediated signaling pathways to affect behavior". Neuron. 53 (3): 439—52. doi:10.1016/j.neuron.2007.01.008. PMID 17270739.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)
  3. ↑ Cussac D, Boutet-Robinet E, Ailhaud MC, Newman-Tancredi A, Martel JC, Danty N, Rauly-Lestienne I (October 2008). "Agonist-directed trafficking of signalling at serotonin 5-HT2A, 5-HT2B and 5-HT2C-VSV receptors mediated Gq/11 activation and calcium mobilisation in CHO cells". Eur. J. Pharmacol. 594 (1–3): 32—8. doi:10.1016/j.ejphar.2008.07.040. PMID 18703043.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)
  4. ↑ Schmid CL, Raehal KM, Bohn LM (2008). "Agonist-directed signaling of the serotonin 2A receptor depends on beta-arrestin-2 interactions in vivo". Proceedings of the National Academy of Sciences of the United States of America. 105 (3): 1079—84. doi:10.1073/pnas.0708862105. PMC 2242710. PMID 18195357.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)
  5. ↑ Abbas A, Roth BL (2008). "Arresting serotonin". Proceedings of the National Academy of Sciences of the United States of America. 105 (3): 831—2. doi:10.1073/pnas.0711335105. PMC 2242676. PMID 18195368.
  6. ↑ Parker MA, Kurrasch DM, Nichols DE (2008). "The role of lipophilicity in determining binding affinity and functional activity for 5-HT2A receptor ligands". Bioorg. Med. Chem. 16 (8): 4661—9. doi:10.1016/j.bmc.2008.02.033. PMC 2442558. PMID 18296055.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)
  7. ↑ OSIRIS search results. Gene: HTR2A. Supplementary material to article
    • Chambers JJ, Kurrasch-Orbaugh DM, Parker MA, Nichols DE (March 2001). "Enantiospecific synthesis and pharmacological evaluation of a series of super-potent, conformationally restricted 5-HT(2A/2C) receptor agonists". Journal of Medical Chemistry. 44 (6): 1003—10. doi:10.1021/jm000491y. PMID 11300881.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)
  8. ↑ Chee IS, Lee SW, Kim JL, Wang SK, Shin YO, Shin SC, Lee YH, Hwang HM, Lim MR (2001). "5-HT2A receptor gene promoter polymorphism -1438A/G and bipolar disorder". Psychiatr. Genet. 11 (3): 111—114. doi:10.1097/00041444-200109000-00001. PMID 11702051.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)
  9. ↑ Choi MJ, Lee HJ, Lee HJ, Ham BJ, Cha JH, Ryu SH, Lee MS (2004). "Association between major depressive disorder and the -1438A/G polymorphism of the serotonin 2A receptor gene". Neuropsychobiology. 49 (1): 38—41. doi:10.1159/000075337. PMID 14730199.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)
  10. ↑ Williams J, Spurlock G, McGuffin P, Mallet J, Nöthen MM, Gill M, Aschauer H, Nylander PO, Macciardi F, Owen MJ (1996). "Association between schizophrenia and T102C polymorphism of the 5-hydroxytryptamine type 2a-receptor gene. European Multicentre Association Study of Schizophrenia (EMASS) Group". The Lancet. 347 (9011): 1294—1296. doi:10.1016/s0140-6736(96)90939-3. PMID 8622505.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)
  11. ↑ 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 (July 2008). "Association study of two polymorphisms of the serotonin-2A receptor gene and suicide attempts". American Journal of Medical Genetics. 147B (5): 645—9. doi:10.1002/ajmg.b.30642. PMID 18163387.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)
  12. ↑ Gene Overview of All Published Schizophrenia-Association Studies for HTR2A — SzGene database at Schizophrenia Research Forum.
  13. ↑ Serretti A, Drago A, De Ronchi D (2007). "HTR2A gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies". Current medicinal chemistry. 14 (19): 2053—69. doi:10.2174/092986707781368450. PMID 17691947.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)
  14. ↑ 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 (2006). "Variation in the gene encoding the serotonin 2A receptor is associated with outcome of antidepressant treatment". Am. J. Hum. Genet. 78 (5): 804—814. doi:10.1086/503820. PMC 1474035. PMID 16642436.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)
  15. ↑ Laje G, Paddock S, Manji H, Rush AJ, Wilson AF, Charney D, McMahon FJ (2007). "Genetic markers of suicidal ideation emerging during citalopram treatment of major depression". Am J Psychiatry. 164 (10): 1530—1538. doi:10.1176/appi.ajp.2007.06122018. PMID 17898344.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)
  16. ↑ Laje G, McMahon FJ (2007). "The pharmacogenetics of major depression: past, present, and future". Biol. Psychiatry. 62 (11): 1205—1207. doi:10.1016/j.biopsych.2007.09.016. PMID 17949692.
  17. ↑ Smith AK, Dimulescu I, Falkenberg VR, Narasimhan S, Heim C, Vernon SD, Rajeevan MS (2008). "Genetic evaluation of the serotonergic system in chronic fatigue syndrome". Psychoneuroendocrinology. 33 (2): 188—197. doi:10.1016/j.psyneuen.2007.11.001. PMID 18079067.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)
  18. ↑ Lemaire C, Cantineau R, Guillaume M, Plenevaux A, Christiaens L (1 December 1991). "Fluorine-18-altanserin: a radioligand for the study of serotonin receptors with PET: radiolabeling and in vivo biologic behavior in rats". Journal of Nuclear Medicine. 32 (12): 2266—2272. PMID 1744713.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)
  19. ↑ Lundkvist C, Halldin C, Ginovart N, Nyberg S, Swahn CG, Carr AA, Brunner F, Farde L (1996). "11C-MDL 100907, a radioligland for selective imaging of 5-HT2A receptors with positron emission tomography". Life Sci. 58 (10): PL 187–192. doi:10.1016/0024-3205(96)00013-6. PMID 8602111.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)
  20. ↑ Mintun MA, Sheline YI, Moerlein SM, Vlassenko AG, Huang Y, Snyder AZ (2004). "Decreased hippocampal 5-HT2A receptor binding in major depressive disorder: in vivo measurement with [18F]-altanserin positron emission tomography". Biological Psychiatry. 55 (3): 217—24. doi:10.1016/j.biopsych.2003.08.015. PMID 14744461.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)
  21. ↑ Adams KH, Hansen ES, Pinborg LH, Hasselbalch SG, Svarer C, Holm S, Bolwig TG, Knudsen GM (2005). "Patients with obsessive-compulsive disorder have increased 5-HT2A receptor binding in the caudate nuclei". International Journal of Neuropsychopharmacology. 8 (3): 391—401. doi:10.1017/S1461145705005055. PMID 15801987.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)
  22. ↑ Haugbøl S, Pinborg LH, Regeur L, Hansen ES, Bolwig TG, Nielsen FA, Svarer C, Skovgaard LT, Knudsen GM (2007). "Cerebral 5-HT2A receptor binding is increased in patients with Tourette's syndrome". Int. J. Neuropsychopharmacol. 10 (2): 245—52. doi:10.1017/S1461145706006559. PMID 16945163.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)
  23. ↑ Rosier A, Dupont P, Peuskens J, Bormans G, Vandenberghe R, Maes M, de Groot T, Schiepers C, Verbruggen A, Mortelmans L (1996). "Visualisation of loss of 5-HT2A receptors with age in healthy volunteers using [18F]-altanserin and positron emission tomographic imaging". Psychiatry Res. 68 (1): 11—22. doi:10.1016/S0925-4927(96)02806-5. PMID 9027929.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)
  24. ↑ 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 (1998). "Reduced binding of [18F]-altanserin to serotonin type 2A receptors in aging: persistence of effect after partial volume correction". Brain Res. 813 (1): 167—171. doi:10.1016/S0006-8993(98)00909-3. PMID 9824691.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)
  25. ↑ Adams KH, Pinborg LH, Svarer C, Hasselbalch SG, Holm S, Haugbøl S, Madsen K, Frøkjaer V, Martiny L, Paulson OB, Knudsen GM (2004). "A database of [18F]-altanserin binding to 5-HT2A receptors in normal volunteers: normative data and relationship to physiological and demographic variables". NeuroImage. 21 (3): 1105—1113. doi:10.1016/j.neuroimage.2003.10.046. PMID 15006678.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)
  26. ↑ Frokjaer VG, Mortensen EL, Nielsen FA, Haugbol S, Pinborg LH, Adams KH, Svarer C, Hasselbalch SG, Holm S, Paulson OB, Knudsen GM (2008). "Frontolimbic serotonin 2A receptor binding in healthy subjects is associated with personality risk factors for affective disorder". Biological Psychiatry. 63 (6): 569—76. doi:10.1016/j.biopsych.2007.07.009. PMID 17884017.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)
  27. ↑ Ошибка в сносках?: Неверный тег <ref>; для сносок pmid15550673 не указан текст

Для дополнительного чтения

  • Perez-Aguilar JM, Shan J, LeVine MV, Khelashvili G, Weinstein H (2014). "A functional selectivity mechanism at the serotonin-2A GPCR involves ligand-dependent conformations of intracellular loop 2". J. Am. Chem. Soc. doi:10.1021/ja508394x. PMID 25314362.{{cite journal}}: Википедия:Обслуживание CS1 (множественные имена: authors list) (ссылка)

Ссылки

  • 5-HT2A. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
  • MeSH 5-HT2A+Receptor
Источник — https://ru.wikipedia.org/w/index.php?title=5-HT2A-рецептор&oldid=68168439