View source for Biology:5-HT2B receptor

{{Short description|Mammalian protein found in Homo sapiens}}
{{DISPLAYTITLE:5-HT<sub>2B</sub> receptor}}
{{Infobox_gene}}
'''5-Hydroxytryptamine receptor 2B''' ('''5-HT<sub>2B</sub>''') also known as '''serotonin receptor 2B''' is a [[Biology:Protein|protein]] that in humans is encoded by the ''HTR2B'' [[Biology:Gene|gene]].<ref name="entrez_ 3357">{{cite web | title = Entrez Gene: HTR<sub>2B</sub> 5-hydroxytryptamine (serotonin) receptor 2B| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3357}}</ref><ref name="pmid8143856">{{cite journal | vauthors = Schmuck K, Ullmer C, Engels P, Lübbert H | title = Cloning and functional characterization of the human 5-HT2B serotonin receptor | journal = FEBS Letters | volume = 342 | issue = 1 | pages = 85–90 | date = Mar 1994 | pmid = 8143856 | doi = 10.1016/0014-5793(94)80590-3 | s2cid = 11232259 | doi-access = free }}</ref> 5-HT<sub>2B</sub> is a member of the [[Biology:5-HT2 receptor|5-HT<sub>2</sub> receptor]] family that binds the [[Biology:Neurotransmitter|neurotransmitter]] [[Chemistry:Serotonin|serotonin]] (5-hydroxytryptamine, 5-HT). Like all 5-HT<sub>2</sub> receptors, the 5-HT<sub>2B</sub> receptor is G<sub>q</sub>/G<sub>11</sub>-protein coupled, leading to downstream activation of [[Biology:Phospholipase C|phospholipase C]].

== Tissue distribution and function ==
First discovered in the stomach of rats, 5-HT<sub>2B</sub> was challenging to characterize initially because of its structural similarity to the other 5-HT<sub>2</sub> receptors, particularly 5-HT<sub>2C</sub>.<ref>{{cite book |last1=Frazer |first1=Alan |last2=Hensler |first2=Julie G. |date=1999 |chapter=Serotonin |url=https://www.ncbi.nlm.nih.gov/books/NBK28150/ |title=Basic Neurochemistry: Molecular, Cellular and Medical Aspects |publisher=Lippincott-Raven |edition=6th|language=en}}</ref> The 5-HT<sub>2</sub> receptors (of which the 5-HT<sub>2B</sub> receptor is a subtype) mediate many of the central and peripheral physiologic functions of [[Chemistry:Serotonin|serotonin]]. Cardiovascular effects include contraction of blood vessels and shape changes in platelets; central nervous system (CNS) effects include neuronal sensitization to tactile stimuli and mediation of some of the effects of [[Unsolved:Hallucinogen|hallucinogen]]ic substituted amphetamines. The 5-HT<sub>2B</sub> receptor is expressed in several areas of the CNS, including the dorsal hypothalamus, frontal cortex, medial amygdala, and meninges.<ref name="Bonhaus_1995">{{cite journal | vauthors = Bonhaus DW, Bach C, DeSouza A, Salazar FH, Matsuoka BD, Zuppan P, Chan HW, Eglen RM | title = The pharmacology and distribution of human 5-hydroxytryptamine2B (5-HT2B) receptor gene products: comparison with 5-HT2A and 5-HT2C receptors | journal = British Journal of Pharmacology | volume = 115 | issue = 4 | pages = 622–8 | date = June 1995 | pmid = 7582481 | pmc = 1908489 | doi = 10.1111/j.1476-5381.1995.tb14977.x }}</ref> However, its most important role is in the peripheral nervous system (PNS) where it maintains the viability and efficiency of the cardiac valve leaflets.<ref>{{cite book |url=https://www.worldcat.org/oclc/712018683 |title=XPharm : the comprehensive pharmacology reference |date=2008 |publisher=Elsevier |others=S. J. Enna, David B. Bylund, Elsevier Science |isbn=978-0-08-055232-3 |location=Amsterdam |oclc=712018683}}</ref>

The 5-HT<sub>2B</sub> receptor subtype is involved in:
* CNS: inhibition of serotonin and dopamine uptake, behavioral effects<ref name="pmid18337424">{{cite journal | vauthors = Doly S, Valjent E, Setola V, Callebert J, Hervé D, Launay JM, Maroteaux L | title = Serotonin 5-HT2B receptors are required for 3,4-methylenedioxymethamphetamine-induced hyperlocomotion and 5-HT release in vivo and in vitro | journal = The Journal of Neuroscience | volume = 28 | issue = 11 | pages = 2933–40 | date = Mar 2008 | pmid = 18337424 | pmc = 6670669 | doi = 10.1523/JNEUROSCI.5723-07.2008 }}</ref>
* Vascular: pulmonary [[Chemistry:Vasoconstriction|vasoconstriction]]<ref name="pmid12244304">{{cite journal | vauthors = Launay JM, Hervé P, Peoc'h K, Tournois C, Callebert J, Nebigil CG, Etienne N, Drouet L, Humbert M, Simonneau G, Maroteaux L | title = Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension | journal = Nature Medicine | volume = 8 | issue = 10 | pages = 1129–35 | date = Oct 2002 | pmid = 12244304 | doi = 10.1038/nm764 | s2cid = 20736218 | url = https://hal.archives-ouvertes.fr/hal-01985063/file/NM_final_rev.pdf }}</ref>
* Cardiac: The 5-HT<sub>2B</sub> receptor regulates cardiac structure and functions, as demonstrated by the abnormal cardiac development observed in 5-HT<sub>2B</sub> receptor null mice.<ref name="pmid11413089">{{cite journal | vauthors = Nebigil CG, Hickel P, Messaddeq N, Vonesch JL, Douchet MP, Monassier L, György K, Matz R, Andriantsitohaina R, Manivet P, Launay JM, Maroteaux L | title = Ablation of serotonin 5-HT(2B) receptors in mice leads to abnormal cardiac structure and function | journal = Circulation | volume = 103 | issue = 24 | pages = 2973–9 | date = Jun 2001 | pmid = 11413089 | doi = 10.1161/01.cir.103.24.2973 | doi-access = free }}</ref> Excessive stimulation of this receptor causes pathological proliferation of cardiac valve fibroblasts,<ref name="pmid18511249">{{cite journal | vauthors = Elangbam CS, Job LE, Zadrozny LM, Barton JC, Yoon LW, Gates LD, Slocum N | title = 5-hydroxytryptamine (5HT)-induced valvulopathy: compositional valvular alterations are associated with 5HT2B receptor and 5HT transporter transcript changes in Sprague-Dawley rats | journal = Experimental and Toxicologic Pathology | volume = 60 | issue = 4–5 | pages = 253–62 | date = Aug 2008 | pmid = 18511249 | doi = 10.1016/j.etp.2008.03.005 }}</ref> with chronic overstimulation leading to valvulopathy.<ref>{{cite journal |last1=Padhariya |first1=Komal |last2=Bhandare |first2=Richie |last3=Canney |first3=Daniel |last4=Velingkar |first4=Vinay |date=2017-12-12 |title=Cardiovascular Concern of 5-HT2B Receptor and Recent Vistas in the Development of Its Antagonists |url=http://www.eurekaselect.com/153656/article |journal=Cardiovascular & Hematological Disorders Drug Targets |language=en |volume=17 |issue=2 |pages=86–104 |doi=10.2174/1871529X17666170703115111|pmid=28676029 }}</ref><ref>{{Citation |last=Neugebauer |first=Volker |title=Handbook of the Behavioral Neurobiology of Serotonin |chapter=Serotonin—pain modulation |date=2020 |chapter-url=http://dx.doi.org/10.1016/b978-0-444-64125-0.00017-7 |series=Handbook of Behavioral Neuroscience |volume=31 |pages=309–320 |publisher=Elsevier |doi=10.1016/b978-0-444-64125-0.00017-7 |isbn=9780444641250 |s2cid=212837146 |access-date=2022-07-04}}</ref> These receptors are also overexpressed in human failing heart and antagonists of 5-HT<sub>2B</sub> receptors were discovered to prevent both angiotensin II or beta-adrenergic agonist-induced pathological cardiac hypertrophy in mouse.<ref name="pmid15302781">{{cite journal | vauthors = Jaffré F, Callebert J, Sarre A, Etienne N, Nebigil CG, Launay JM, Maroteaux L, Monassier L | title = Involvement of the serotonin 5-HT2B receptor in cardiac hypertrophy linked to sympathetic stimulation: control of interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha cytokine production by ventricular fibroblasts | journal = Circulation | volume = 110 | issue = 8 | pages = 969–74 | date = Aug 2004 | pmid = 15302781 | doi = 10.1161/01.CIR.0000139856.20505.57 | doi-access = free }}</ref><ref name="pmid18591460">{{cite journal | vauthors = Monassier L, Laplante MA, Jaffré F, Bousquet P, Maroteaux L, de Champlain J | title = Serotonin 5-HT(2B) receptor blockade prevents reactive oxygen species-induced cardiac hypertrophy in mice | journal = Hypertension | volume = 52 | issue = 2 | pages = 301–7 | date = Aug 2008 | pmid = 18591460 | doi = 10.1161/HYPERTENSIONAHA.107.105551 | doi-access = free }}</ref><ref name="pmid19023134">{{cite journal | vauthors = Jaffré F, Bonnin P, Callebert J, Debbabi H, Setola V, Doly S, Monassier L, Mettauer B, Blaxall BC, Launay JM, Maroteaux L | title = Serotonin and angiotensin receptors in cardiac fibroblasts coregulate adrenergic-dependent cardiac hypertrophy | journal = Circulation Research | volume = 104 | issue = 1 | pages = 113–23 | date = Jan 2009 | pmid = 19023134 | doi = 10.1161/CIRCRESAHA.108.180976 | doi-access = free }}</ref>
* [[Biology:Serotonin transporter|Serotonin transporter]]: 5-HT<sub>2B</sub> receptors regulate serotonin release via the serotonin transporter, and are important both to normal physiological regulation of serotonin levels in blood plasma,<ref name="pmid16461587">{{cite journal | vauthors = Callebert J, Esteve JM, Hervé P, Peoc'h K, Tournois C, Drouet L, Launay JM, Maroteaux L | title = Evidence for a control of plasma serotonin levels by 5-hydroxytryptamine(2B) receptors in mice | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 317 | issue = 2 | pages = 724–31 | date = May 2006 | pmid = 16461587 | doi = 10.1124/jpet.105.098269 | s2cid = 16099098 | url = https://hal.archives-ouvertes.fr/hal-01274937/file/Callebert0206.pdf }}</ref> and with the abnormal acute serotonin release produced by drugs such as [[Chemistry:MDMA|MDMA]].<ref name="pmid18337424"/> Surprisingly, however, 5-HT<sub>2B</sub> receptor activation appears to be protective against the development of [[Medicine:Serotonin syndrome|serotonin syndrome]] following elevated extracellular serotonin levels,<ref name="pmid21277875">{{cite journal | vauthors = Diaz SL, Maroteaux L | title = Implication of 5-HT(2B) receptors in the serotonin syndrome | journal = Neuropharmacology | volume = 61 | issue = 3 | pages = 495–502 | date = Sep 2011 | pmid = 21277875 | doi = 10.1016/j.neuropharm.2011.01.025 | s2cid = 14905808 | url = http://www.hal.inserm.fr/inserm-00561473 }}</ref> despite its role in modulating serotonin release.

== Clinical significance ==

5-HT<sub>2B</sub> receptors have been strongly implicated in causing drug-induced [[Medicine:Valvular heart disease|valvular heart disease]].<ref name="pmid11104741">{{cite journal | vauthors = Rothman RB, Baumann MH, Savage JE, Rauser L, McBride A, Hufeisen SJ, Roth BL|author7-link=Bryan Roth | title = Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications | journal = Circulation | volume = 102 | issue = 23 | pages = 2836–41 | date = Dec 2000 | pmid = 11104741 | doi = 10.1161/01.CIR.102.23.2836 | doi-access = free }}</ref><ref name="pmid10617681">{{cite journal | vauthors = Fitzgerald LW, Burn TC, Brown BS, Patterson JP, Corjay MH, Valentine PA, Sun JH, Link JR, Abbaszade I, Hollis JM, Largent BL, Hartig PR, Hollis GF, Meunier PC, Robichaud AJ, Robertson DW | title = Possible role of valvular serotonin 5-HT(2B) receptors in the cardiopathy associated with fenfluramine | journal = Molecular Pharmacology | volume = 57 | issue = 1 | pages = 75–81 | date = Jan 2000 | pmid = 10617681 }}</ref><ref name="pmid17202450">{{cite journal | vauthors = Roth BL | title = Drugs and valvular heart disease | journal = The New England Journal of Medicine | volume = 356 | issue = 1 | pages = 6–9 | date = Jan 2007 | pmid = 17202450 | doi = 10.1056/NEJMp068265 }}</ref> The Fen-Phen scandal in the 80s and 90s revealed the cardiotoxic effects of 5-HT<sub>2B</sub> stimulation.<ref>{{cite web |title=Archive: How Fen-Phen, a Diet 'Miracle,' Rose and Fell |url=https://archive.nytimes.com/www.nytimes.com/partners/aol/special/women/warchive/970923_1080.html |access-date=2022-07-04 |website=archive.nytimes.com}}</ref>  Today, 5-HT<sub>2B</sub> agonism is considered a toxicity signal precluding further clinical development of a compound.<ref>{{cite journal |last1=Cavero |first1=Icilio |last2=Guillon |first2=Jean-Michel |date=2014-03-01 |title=Safety Pharmacology assessment of drugs with biased 5-HT2B receptor agonism mediating cardiac valvulopathy |url=https://www.sciencedirect.com/science/article/pii/S1056871913003262 |journal=Journal of Pharmacological and Toxicological Methods |language=en |volume=69 |issue=2 |pages=150–161 |doi=10.1016/j.vascn.2013.12.004 |pmid=24361689 |issn=1056-8719}}</ref> 

==Ligands==
The structure of the 5-HT<sub>2B</sub> receptor was resolved in a complex with the valvulopathogenic drug [[Chemistry:Ergotamine|ergotamine]].<ref name="pmid23519215">{{PDB|4IB4}}; {{cite journal |vauthors=Wacker D, Wang C, Katritch V, Han GW, Huang XP, Vardy E, McCorvy JD, Jiang Y, Chu M, Siu FY, Liu W, Xu HE, Cherezov V, Roth BL, Stevens RC |date=May 2013 |title=Structural features for functional selectivity at serotonin receptors |journal=Science |volume=340 |issue=6132 |pages=615–9 |bibcode=2013Sci...340..615W |doi=10.1126/science.1232808 |pmc=3644390 |pmid=23519215}}</ref> As of 2009, few highly selective 5-HT<sub>2B</sub> receptor ligands have been discovered, although numerous potent non-selective compounds are known, particularly agents with concomitant [[Biology:5-HT2C receptor|5-HT<sub>2C</sub>]] binding. Research in this area has been limited due to the cardiotoxicity of 5-HT<sub>2B</sub> agonists, and the lack of clear therapeutic application for 5-HT<sub>2B</sub> antagonists, but there is still a need for selective ligands for scientific research.<ref name="Schuhmacher">{{cite thesis | author = Schuhmacher M | title = [Chiral arylmethoxytryptamines as 5-HT<sub>2B</sub>-receptor antagonists: synthesis, analysis and in-vitro pharmacology] (German) | version = Ph.D. Dissertation | publisher = University of Regensburg | year = 2007 | pages = 6–17 | url = http://www.opus-bayern.de/uni-regensburg/volltexte/2008/796/pdf/Dissertation_Schumacher.pdf | access-date = 2008-08-11 | archive-date = 2011-07-18 | archive-url = https://web.archive.org/web/20110718063551/http://www.opus-bayern.de/uni-regensburg/volltexte/2008/796/pdf/Dissertation_Schumacher.pdf | url-status = dead }}</ref>

===Agonists===
;Selective
* [[Chemistry:BW-723C86|BW-723C86]]<ref name="pmid10498829">{{cite journal | vauthors = Porter RH, Benwell KR, Lamb H, Malcolm CS, Allen NH, Revell DF, Adams DR, Sheardown MJ | title = Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells | journal = British Journal of Pharmacology | volume = 128 | issue = 1 | pages = 13–20 | date = Sep 1999 | pmid = 10498829 | pmc = 1571597 | doi = 10.1038/sj.bjp.0702751 }}</ref>{{snd}} fair functional subtype selectivity; almost full agonist. Anxiolytic ''in vivo''<ref name="pmid9886683">{{cite journal | vauthors = Kennett GA, Trail B, Bright F | title = Anxiolytic-like actions of BW 723C86 in the rat Vogel conflict test are 5-HT2B receptor mediated | journal = Neuropharmacology | volume = 37 | issue = 12 | pages = 1603–10 | date = Dec 1998 | pmid = 9886683 | doi = 10.1016/S0028-3908(98)00115-4 | s2cid = 7310462 }}</ref>
* [[Chemistry:Ro60-0175|Ro60-0175]]<ref name="pmid10498829"/>{{snd}} functionally selective over [[Biology:5-HT2A receptor|5-HT<sub>2A</sub>]], potent agonist at both 5-HT<sub>2B/C</sub>
* [[Chemistry:VER-3323|VER-3323]]{{snd}} selective for 5-HT<sub>2B/C</sub> over 5-HT<sub>2A</sub>
* α-Methyl-5-HT{{snd}} moderately selective over 5-HT<sub>2A/C</sub>
* [[Chemistry:6-APB|6-APB]]
* [[Chemistry:LY-266,097|LY-266,097]]{{snd}} biased partial agonist in favor of G<sub>q</sub> protein, no β-arrestin2 recruitment<ref name="pmid30127358">{{cite journal | vauthors = McCorvy JD, Wacker D, Wang S, Agegnehu B, Liu J, Lansu K, Tribo AR, Olsen RH, Che T, Jin J, Roth BL | display-authors = 6 | title = Structural determinants of 5-HT2B receptor activation and biased agonism | journal = Nature Structural & Molecular Biology | volume =  25| issue =  9| pages = 787–796 | date = August 2018 | pmid = 30127358 | pmc = 6237183 | doi = 10.1038/s41594-018-0116-7 }}</ref>

;
;Non-selective
* [[Chemistry:Guanfacine|Guanfacine]]{{snd}} an [[Biology:Alpha-2A adrenergic receptor|α<sub>2A</sub>]] agonist, but has 5-HT<sub>2B</sub> agonistic activity at therapeutic concentrations.<ref>{{cite journal | vauthors = Huang XP, Setola V, Yadav PN, Allen JA, Rogan SC, Hanson BJ, Revankar C, Robers M, Doucette C, Roth BL | title = Parallel functional activity profiling reveals valvulopathogens are potent 5-hydroxytryptamine(2B) receptor agonists: implications for drug safety assessment | journal = Molecular Pharmacology | volume = 76 | issue = 4 | date = Oct 2009 | pmid = 19570945 | doi = 10.1124/mol.109.058057 | pmc=2769050 | pages=710–22}}</ref>
* [[Chemistry:MDMA|MDMA]]<ref name="MDx">{{cite journal | vauthors = Setola V, Hufeisen SJ, Grande-Allen KJ, Vesely I, Glennon RA, Blough B, Rothman RB, Roth BL |  title = 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro | journal = Molecular Pharmacology | volume = 63 | issue = 6 | pages = 1223&ndash;1229 | date = Jun 2003 | pmid = 12761331 | doi = 10.1124/mol.63.6.1223 | s2cid=839426 | url = https://www.researchgate.net/publication/10748715 }}</ref>
* MDA<ref name="MDx"/>
* [[Chemistry:2,5-Dimethoxy-4-ethoxyamphetamine|MEM]]<ref name="pmid20126400">{{cite journal | vauthors = Ray TS | title = Psychedelics and the human receptorome | journal = PLOS ONE | volume = 5 | issue = 2 | pages = e9019 | year = 2010 | pmid = 20126400 | pmc = 2814854 | doi = 10.1371/journal.pone.0009019 | editor1-last = Manzoni | editor1-first = Olivier Jacques | bibcode = 2010PLoSO...5.9019R | doi-access = free }}</ref>
* [[Chemistry:Pergolide|Pergolide]]<ref name="pmid18096760">{{cite journal | vauthors = Görnemann T, Hübner H, Gmeiner P, Horowski R, Latté KP, Flieger M, Pertz HH | title = Characterization of the molecular fragment that is responsible for agonism of pergolide at serotonin 5-Hydroxytryptamine2B and 5-Hydroxytryptamine2A receptors | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 324 | issue = 3 | pages = 1136–45 | date = Mar 2008 | pmid = 18096760 | doi = 10.1124/jpet.107.133165 | s2cid = 24907300 }}</ref>
* [[Chemistry:Cabergoline|Cabergoline]]
* [[Chemistry:Norfenfluramine|Norfenfluramine]]<ref name="pmid10498829"/>
* [[Chemistry:Chlorphentermine|Chlorphentermine]]
* [[Chemistry:Aminorex|Aminorex]]
* Bromo-dragonfly
* DMT
* [[Chemistry:5-MeO-DMT|5-MeO-DMT]]
* [[Chemistry:LSD|LSD]]{{snd}} about equal affinity for human cloned 5-HT<sub>2B</sub> and [[Biology:5-HT2A receptor|5-HT<sub>2A</sub> receptors]]<ref name="pdsp.med.unc.edu"/>
* [[Chemistry:Psilocin|Psilocin]]<ref name="pdsp.med.unc.edu">{{cite web|url=https://pdsp.unc.edu/databases/kidb.php |title=PDSP Ki database, University of North Carolina at Chapel Hill |access-date=2019-09-04}}</ref>
*[[Chemistry:Xylometazoline|Xylometazoline]]
*[[Chemistry:Oxymetazoline|Oxymetazoline]]
*[[Chemistry:Quinidine|Quinidine]]
*[[Chemistry:Ropinirole|Ropinirole]]
*[[Chemistry:Fenoldopam|Fenoldopam]]
*[[Chemistry:Lorcaserin|Lorcaserin]]
*[[Chemistry:Methylergometrine|Methylergonovine]]
*[[Chemistry:Ergotamine|Ergotamine]]
*[[Chemistry:Ergometrine|Ergonovine]]

===Antagonists===
* [[Chemistry:Agomelatine|Agomelatine]]{{snd}} primarily a [[Chemistry:Melatonin|melatonin]] [[Chemistry:Melatonin receptor agonist|MT<sub>1</sub>/MT<sub>2</sub> receptor agonist]], with a less potent antagonism of 5-HT<sub>2B</sub> and [[Biology:5-HT2C receptor|5-HT<sub>2C</sub>]]<ref>{{cite journal | vauthors = Millan MJ, Gobert A, Lejeune F, Dekeyne A, Newman-Tancredi A, Pasteau V, Rivet JM, Cussac D | title = The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 306 | issue = 3 | pages = 954–64 | date = Sep 2003 | pmid = 12750432 | doi = 10.1124/jpet.103.051797 | s2cid = 18753440 }}</ref>
* [[Chemistry:Amisulpride|Amisulpride]]
* [[Chemistry:Aripiprazole|Aripiprazole]]
*[[Chemistry:Cariprazine|Cariprazine]]<ref>{{cite journal|last=Garnock-Jones|first=Karly P.|date=June 2017|title=Cariprazine: A Review in Schizophrenia|journal=CNS Drugs|volume=31|issue=6|pages=513–525|doi=10.1007/s40263-017-0442-z|issn=1179-1934|pmid=28560619|s2cid=4392274}}</ref>
* [[Chemistry:Clozapine|Clozapine]]
*[[Chemistry:Cyproheptadine|Cyproheptadine]]
*[[Chemistry:Meta-Chlorophenylpiperazine|mCPP]] (in humans)
* [[Chemistry:Sarpogrelate|Sarpogrelate]]{{snd}} a mixed 5-HT<sub>2A/B</sub> antagonist
* [[Chemistry:Lisuride|Lisuride]]{{snd}} a [[Chemistry:Dopamine agonist|dopamine agonist]] of the [[Chemistry:Ergoline|ergoline]] class, that is also a 5-HT<sub>2B</sub> antagonist<ref name="pmid16614540">{{cite journal | vauthors = 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 = Clinical Neuropharmacology | volume = 29 | issue = 2 | pages = 80–6 | year = 2006 | pmid = 16614540 | doi = 10.1097/00002826-200603000-00005 | s2cid = 33849447 }}</ref> and a dual 5-HT<sub>2A/C</sub> agonist<ref name="pmid9600588">{{cite journal | vauthors = 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 | volume = 136 | issue = 4 | pages = 409–14 | date = Apr 1998 | pmid = 9600588 | doi = 10.1007/s002130050585 | s2cid = 3021798 }}</ref>
* [[Chemistry:Tegaserod|Tegaserod]]{{snd}} primarily a 5-HT<sub>4</sub> agonist, but also a 5-HT<sub>2B</sub> antagonist<ref>{{cite journal | vauthors = Beattie DT, Smith JA, Marquess D, Vickery RG, Armstrong SR, Pulido-Rios T, McCullough JL, Sandlund C, Richardson C, Mai N, Humphrey PP | title = The 5-HT4 receptor agonist, tegaserod, is a potent 5-HT2B receptor antagonist in vitro and in vivo | journal = British Journal of Pharmacology | volume = 143 | issue = 5 | pages = 549–60 | date = Nov 2004 | pmid = 15466450 | pmc = 1575425 | doi = 10.1038/sj.bjp.0705929 }}</ref>
* RS-127,445<ref name="pmid10455251">{{cite journal | vauthors = Bonhaus DW, Flippin LA, Greenhouse RJ, Jaime S, Rocha C, Dawson M, Van Natta K, Chang LK, Pulido-Rios T, Webber A, Leung E, Eglen RM, Martin GR | title = RS-127445: a selective, high affinity, orally bioavailable 5-HT2B receptor antagonist | journal = British Journal of Pharmacology | volume = 127 | issue = 5 | pages = 1075–82 | date = Jul 1999 | pmid = 10455251 | pmc = 1566110 | doi = 10.1038/sj.bjp.0702632 }}</ref>{{snd}} high affinity; subtype selective (1000×), selective over at least eight other 5-HTR types; orally bioavailable
*[[Chemistry:Metadoxine|Metadoxine]]{{snd}} a 5-HT<sub>2B</sub> antagonist and GABA-activity modulator<ref name=alcobra>{{cite web|url=http://www.alcobra-pharma.com/products.cfm?productID=142236|title=Metadoxine extended release (MDX) for adult ADHD|publisher=Alcobra Ltd|date=2014|access-date=2014-05-07|archive-date=2019-02-13|archive-url=https://web.archive.org/web/20190213005751/http://www.alcobra-pharma.com/products.cfm?productID=142236|url-status=dead}}</ref>
* [[Chemistry:SDZ SER-082|SDZ SER-082]]{{snd}} a mixed 5-HT<sub>2B/C</sub> antagonist
*[[Chemistry:Promethazine|Promethazine]]<ref>{{cite web|url=http://www.guidetopharmacology.org/GRAC/LigandActivityRangeVisForward?ligandId=7282|title=promethazine {{!}} Activity data visualisation tool {{!}} IUPHAR/BPS Guide to PHARMACOLOGY|website=www.guidetopharmacology.org|access-date=2019-02-28}}</ref>
* [[Chemistry:EGIS-7625|EGIS-7625]]{{snd}} high selectivity over 5-HT<sub>2A</sub><ref name="pmid15107597">{{cite journal | vauthors = Kovács A, Gacsályi I, Wellmann J, Schmidt E, Szücs Z, Dubreuil V, Nicolas JP, Boutin J, Bózsing D, Egyed A, Tihanyi K, Spedding M, Szénási G | title = Effects of EGIS-7625, a selective and competitive 5-HT2B receptor antagonist | journal = Cardiovascular Drugs and Therapy | volume = 17 | issue = 5–6 | pages = 427–34 | year = 2003 | pmid = 15107597 | doi = 10.1023/B:CARD.0000015857.96371.43 | s2cid = 11532969 }}</ref>
* PRX-08066
* [[Chemistry:SB-200646|SB-200,646]]
* SB-204,741
* SB-206,553{{snd}} mixed 5-HT<sub>2B/C</sub> antagonist and PAM at [[Biology:Alpha-7 nicotinic receptor#PAMs|α<sub>7</sub> nAChR]]<ref name="pmid19050173">{{cite journal | vauthors = Dunlop J, Lock T, Jow B, Sitzia F, Grauer S, Jow F, Kramer A, Bowlby MR, Randall A, Kowal D, Gilbert A, Comery TA, Larocque J, Soloveva V, Brown J, Roncarati R | title = Old and new pharmacology: positive allosteric modulation of the alpha7 nicotinic acetylcholine receptor by the 5-hydroxytryptamine(2B/C) receptor antagonist SB-206553 (3,5-dihydro-5-methyl-N-3-pyridinylbenzo[1,2-b:4,5-b']di pyrrole-1(2H)-carboxamide) | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 328 | issue = 3 | pages = 766–76 | date = Mar 2009 | pmid = 19050173 | doi = 10.1124/jpet.108.146514 | s2cid = 206500076 }}</ref>
* SB-215,505<ref name="pmid10188965">{{cite journal | vauthors = Reavill C, Kettle A, Holland V, Riley G, Blackburn TP | title = Attenuation of haloperidol-induced catalepsy by a 5-HT2C receptor antagonist | journal = British Journal of Pharmacology | volume = 126 | issue = 3 | pages = 572–4 | date = Feb 1999 | pmid = 10188965 | pmc = 1565856 | doi = 10.1038/sj.bjp.0702350 }}</ref>
* SB-228,357
* Terguride{{snd}} an oral, potent antagonist of 5-HT<sub>2A</sub> and 5-HT<sub>2B</sub> receptors
* [[Chemistry:LY-266,097|LY-266,097]]
* [[Chemistry:LY-272,015|LY-272,015]]

==Possible applications==
5-HT<sub>2B</sub> antagonists have previously been proposed as treatment for migraine headaches, and RS-127,445 was trialled in humans up to Phase I for this indication, but development was not continued.<ref>{{cite journal | vauthors = Poissonnet G, Parmentier JG, Boutin JA, Goldstein S | title = The emergence of selective 5-HT 2B antagonists structures, activities and potential therapeutic applications | journal = Mini Reviews in Medicinal Chemistry | volume = 4 | issue = 3 | pages = 325–30 | date = Mar 2004 | pmid = 15032678 | doi = 10.2174/1389557043487312 }}</ref> More recent research has focused on possible application of 5-HT<sub>2B</sub> antagonists as treatments for chronic heart disease.<ref name="pmid19118279">{{cite journal | vauthors = Shyu KG | title = Serotonin 5-HT2B receptor in cardiac fibroblast contributes to cardiac hypertrophy: a new therapeutic target for heart failure? | journal = Circulation Research | volume = 104 | issue = 1 | pages = 1–3 | date = Jan 2009 | pmid = 19118279 | doi = 10.1161/CIRCRESAHA.108.191122 | s2cid = 41931843 | doi-access =  }}</ref><ref name="pmid19307114">{{cite journal | vauthors = Moss N, Choi Y, Cogan D, Flegg A, Kahrs A, Loke P, Meyn O, Nagaraja R, Napier S, Parker A, Thomas Peterson J, Ramsden P, Sarko C, Skow D, Tomlinson J, Tye H, Whitaker M | title = A new class of 5-HT2B antagonists possesses favorable potency, selectivity, and rat pharmacokinetic properties | journal = Bioorganic & Medicinal Chemistry Letters | volume = 19 | issue = 8 | pages = 2206–10 | date = Apr 2009 | pmid = 19307114 | doi = 10.1016/j.bmcl.2009.02.126 }}</ref> Research claims serotonin 5-HT<sub>2B</sub> receptors have effect on liver regeneration.<ref name="pmid22120177">{{cite journal | vauthors = Ebrahimkhani MR, Oakley F, Murphy LB, Mann J, Moles A, Perugorria MJ, Ellis E, Lakey AF, Burt AD, Douglass A, Wright MC, White SA, Jaffré F, Maroteaux L, Mann DA | title = Stimulating healthy tissue regeneration by targeting the 5-HT<sub>2</sub>B receptor in chronic liver disease | journal = Nature Medicine | volume = 17 | issue = 12 | pages = 1668–73 | date = Dec 2011 | pmid = 22120177 | pmc = 3428919 | doi = 10.1038/nm.2490 }}</ref> Antagonism of 5-HT<sub>2B</sub> may attenuate fibrogenesis and improve liver function in disease models in which fibrosis is pre-established and progressive.

== See also ==
* [[Biology:5-HT receptor|5-HT receptor]]

== References ==
{{Reflist|33em}}

== Further reading ==
{{refbegin|colwidth=33em}}
* {{cite journal | vauthors = Raymond JR, Mukhin YV, Gelasco A, Turner J, Collinsworth G, Gettys TW, Grewal JS, Garnovskaya MN | title = Multiplicity of mechanisms of serotonin receptor signal transduction | journal = Pharmacology & Therapeutics | volume = 92 | issue = 2–3 | pages = 179–212 | year = 2002 | pmid = 11916537 | doi = 10.1016/S0163-7258(01)00169-3 }}
* {{cite journal | vauthors = Choi DS, Birraux G, Launay JM, Maroteaux L | title = The human serotonin 5-HT2B receptor: pharmacological link between 5-HT2 and 5-HT1D receptors | journal = FEBS Letters | volume = 352 | issue = 3 | pages = 393–9 | date = Oct 1994 | pmid = 7926008 | doi = 10.1016/0014-5793(94)00968-6 | s2cid = 26931598 | doi-access =  }}
* {{cite journal | vauthors = Kursar JD, Nelson DL, Wainscott DB, Baez M | title = Molecular cloning, functional expression, and mRNA tissue distribution of the human 5-hydroxytryptamine2B receptor | journal = Molecular Pharmacology | volume = 46 | issue = 2 | pages = 227–34 | date = Aug 1994 | pmid = 8078486 }}
* {{cite journal | vauthors = Schmuck K, Ullmer C, Engels P, Lübbert H | title = Cloning and functional characterization of the human 5-HT2B serotonin receptor | journal = FEBS Letters | volume = 342 | issue = 1 | pages = 85–90 | date = Mar 1994 | pmid = 8143856 | doi = 10.1016/0014-5793(94)80590-3 | s2cid = 11232259 | doi-access = free }}
* {{cite journal | vauthors = Launay JM, Birraux G, Bondoux D, Callebert J, Choi DS, Loric S, Maroteaux L | title = Ras involvement in signal transduction by the serotonin 5-HT2B receptor | journal = The Journal of Biological Chemistry | volume = 271 | issue = 6 | pages = 3141–7 | date = Feb 1996 | pmid = 8621713 | doi = 10.1074/jbc.271.6.3141 | doi-access = free }}
* {{cite journal | vauthors = Le Coniat M, Choi DS, Maroteaux L, Launay JM, Berger R | title = The 5-HT2B receptor gene maps to 2q36.3-2q37.1 | journal = Genomics | volume = 32 | issue = 1 | pages = 172–3 | date = Feb 1996 | pmid = 8786115 | doi = 10.1006/geno.1996.0101 | url = https://hal.archives-ouvertes.fr/hal-03721346/file/Genomics32_172_2B.pdf }}
* {{cite journal | vauthors = Kim SJ, Veenstra-VanderWeele J, Hanna GL, Gonen D, Leventhal BL, Cook EH | title = Mutation screening of human 5-HT(2B)receptor gene in early-onset obsessive-compulsive disorder | journal = Molecular and Cellular Probes | volume = 14 | issue = 1 | pages = 47–52 | date = Feb 2000 | pmid = 10722792 | doi = 10.1006/mcpr.1999.0281 }}
* {{cite journal | vauthors = Manivet P, Mouillet-Richard S, Callebert J, Nebigil CG, Maroteaux L, Hosoda S, Kellermann O, Launay JM | title = PDZ-dependent activation of nitric-oxide synthases by the serotonin 2B receptor | journal = The Journal of Biological Chemistry | volume = 275 | issue = 13 | pages = 9324–31 | date = Mar 2000 | pmid = 10734074 | doi = 10.1074/jbc.275.13.9324 | doi-access = free }}
* {{cite journal | vauthors = Becamel C, Figge A, Poliak S, Dumuis A, Peles E, Bockaert J, Lubbert H, Ullmer C | title = Interaction of serotonin 5-hydroxytryptamine type 2C receptors with PDZ10 of the multi-PDZ domain protein MUPP1 | journal = The Journal of Biological Chemistry | volume = 276 | issue = 16 | pages = 12974–82 | date = Apr 2001 | pmid = 11150294 | doi = 10.1074/jbc.M008089200 | doi-access =free  }}
* {{cite journal | vauthors = Manivet P, Schneider B, Smith JC, Choi DS, Maroteaux L, Kellermann O, Launay JM | title = The serotonin binding site of human and murine 5-HT2B receptors: molecular modeling and site-directed mutagenesis | journal = The Journal of Biological Chemistry | volume = 277 | issue = 19 | pages = 17170–8 | date = May 2002 | pmid = 11859080 | doi = 10.1074/jbc.M200195200 | doi-access = free }}
* {{cite journal | vauthors = Borman RA, Tilford NS, Harmer DW, Day N, Ellis ES, Sheldrick RL, Carey J, Coleman RA, Baxter GS | title = 5-HT(2B) receptors play a key role in mediating the excitatory effects of 5-HT in human colon in vitro | journal = British Journal of Pharmacology | volume = 135 | issue = 5 | pages = 1144–51 | date = Mar 2002 | pmid = 11877320 | pmc = 1573235 | doi = 10.1038/sj.bjp.0704571 }}
* {{cite journal | vauthors = Matsuda A, Suzuki Y, Honda G, Muramatsu S, Matsuzaki O, Nagano Y, Doi T, Shimotohno K, Harada T, Nishida E, Hayashi H, Sugano S | title = Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways | journal = Oncogene | volume = 22 | issue = 21 | pages = 3307–18 | date = May 2003 | pmid = 12761501 | doi = 10.1038/sj.onc.1206406 | s2cid = 38880905 | doi-access =  }}
* {{cite journal | vauthors = Slominski A, Pisarchik A, Zbytek B, Tobin DJ, Kauser S, Wortsman J | title = Functional activity of serotoninergic and melatoninergic systems expressed in the skin | journal = Journal of Cellular Physiology | volume = 196 | issue = 1 | pages = 144–53 | date = Jul 2003 | pmid = 12767050 | doi = 10.1002/jcp.10287 | s2cid = 24534729 | doi-access = free }}
* {{cite journal | vauthors = Lin Z, Walther D, Yu XY, Drgon T, Uhl GR | title = The human serotonin receptor 2B: coding region polymorphisms and association with vulnerability to illegal drug abuse | journal = Pharmacogenetics | volume = 14 | issue = 12 | pages = 805–11 | date = Dec 2004 | pmid = 15608559 | doi = 10.1097/00008571-200412000-00003 }}
{{refend}}

== External links ==
* {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2322 | title = 5-HT<sub>2B</sub>  | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology }}
* {{UCSC gene info|HTR2B}}
* {{PDBe-KB2|P41595|5-hydroxytryptamine receptor 2B}}

{{NLM content}}

{{G protein-coupled receptors|g1}}
{{Cell signaling}}
{{Serotonergics}}

{{DEFAULTSORT:5-Ht2b Receptor}}
[[Category:Serotonin receptors]]

{{Sourceattribution|5-HT2B receptor}}