5-HT1B receptor

5-HT_1B receptors are widely distributed throughout the central nervous system with the highest concentrations found in the frontal cortex, basal ganglia, striatum, and the hippocampus.{{cite web | title = 5-hydroxytryptamine (serotonin) receptor 1B, G protein-coupled| url = https://www.genecards.org/cgi-bin/carddisp.pl?gene=HTR1B| access-date = 23 Feb 2013}}

The function of the 5-HT_1B receptor differs depending upon its location. In the frontal cortex, it is believed to act as a terminal receptor inhibiting the release of dopamine. In the basal ganglia and the striatum, evidence suggests 5-HT signaling acts on an autoreceptor, inhibiting the release of serotonin{{cite journal | vauthors = Pytliak M, Vargová V, Mechírová V, Felšöci M | title = Serotonin receptors - from molecular biology to clinical applications | journal = Physiological Research | volume = 60 | issue = 1 | pages = 15–25 | year = 2011 | pmid = 20945968 | doi = 10.33549/physiolres.931903 | doi-access = free }} and decreasing glutamatergic transmission by reducing miniature excitatory postsynaptic potential (mEPSP) frequency,{{cite journal | vauthors = Huang CC, Yeh CM, Wu MY, Hsu KS | title = A single in vivo cocaine administration impairs 5-HT(1B) receptor-induced long-term depression in the nucleus accumbens | journal = Journal of Neurochemistry | volume = 125 | issue = 6 | pages = 809–21 | date = Jun 2013 | pmid = 23452061 | doi = 10.1111/jnc.12227 | s2cid = 45859780 | doi-access = free }} respectively. In the hippocampus, a recent study has demonstrated that activation of postsynaptic 5-HT_1B heteroreceptors produces a facilitation in excitatory synaptic transmission which is altered in depression.{{cite journal | vauthors = Cai X, Kallarackal AJ, Kvarta MD, Goluskin S, Gaylor K, Bailey AM, Lee HK, Huganir RL, Thompson SM | title = Local potentiation of excitatory synapses by serotonin and its alteration in rodent models of depression | journal = Nature Neuroscience | volume = 16 | issue = 4 | pages = 464–72 | date = Apr 2013 | pmid = 23502536 | doi = 10.1038/nn.3355 | pmc=3609911}}

When the expression of 5-HT_1B in human cortex was traced throughout life, significant changes during adolescence were observed, in a way that is strongly correlated with the expression of 5-HT_1E.{{cite journal | vauthors = Shoval G, Bar-Shira O, Zalsman G, John Mann J, Chechik G | title = Transitions in the transcriptome of the serotonergic and dopaminergic systems in the human brain during adolescence | journal = European Neuropsychopharmacology | volume = 24 | issue = 7 | pages = 1123–32 | date = Jul 2014 | pmid = 24721318 | doi = 10.1016/j.euroneuro.2014.02.009 | s2cid = 14534307 }}

Outside of the CNS, the 5-HT_1B receptor is also expressed on the endothelium of blood vessels, particularly in the meninges.{{cite journal | vauthors = Tepper SJ, Rapoport AM, Sheftell FD | title = Mechanisms of action of the 5-HT1B/1D receptor agonists | journal = Archives of Neurology | volume = 59 | issue = 7 | pages = 1084–1088 | date = July 2002 | pmid = 12117355 | doi = 10.1001/archneur.59.7.1084 | doi-access = free }} Activation of these receptors results in vasoconstriction. The high distribution of vasoconstrictive 5-HT_1B and 5-HT_1D receptors around the brain makes them a valuable drug target for the treatment of migraines.

Blocking 5-HT_1B receptor signalling also increases the number of osteoblasts, bone mass, and the bone formation rate.{{cite journal | vauthors = Yadav VK, Ryu JH, Suda N, Tanaka KF, Gingrich JA, Schütz G, Glorieux FH, Chiang CY, Zajac JD, Insogna KL, Mann JJ, Hen R, Ducy P, Karsenty G | title = Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum | journal = Cell | volume = 135 | issue = 5 | pages = 825–37 | date = Nov 2008 | pmid = 19041748 | pmc = 2614332 | doi = 10.1016/j.cell.2008.09.059}}

• {{lay source|template=cite web |author=Michael Smith |title=Serotonin in Gut Linked to Bone Formation |url=http://www.medpagetoday.com/Endocrinology/Osteoporosis/11923 |website=Medpage Today |archive-url=https://web.archive.org/web/20160303214730/http://www.medpagetoday.com/Endocrinology/Osteoporosis/11923 |archive-date=2016-03-03}}

Knockout mice lacking the 5-HT_1B gene have been reported to have a higher preference for alcohol, although later studies failed to replicate such abnormalities in alcohol consumption.{{cite journal | vauthors = Hoyer D, Hannon JP, Martin GR | title = Molecular, pharmacological and functional diversity of 5-HT receptors | journal = Pharmacology Biochemistry and Behavior | volume = 71 | issue = 4 | pages = 533–54 | date = Apr 2002 | pmid = 11888546 | doi = 10.1016/S0091-3057(01)00746-8 | s2cid = 25543069 }} These mice have also been reported to have a lower measure of anxiety (such as on the elevated plus maze test) and a higher measure of aggression.

Under basal conditions, knockout mice present with a "normal" phenotype and exhibit a sucrose preference (lack of sucrose preference is considered a measure of anhedonia). However, after undergoing chronic unpredictable stress treatment to induce a "depression-like" phenotype these animals do not benefit from administration of selective serotonin reuptake inhibitor (SSRIs).{{Failed verification|date=September 2020}}

Activation of the serotonin 5-HT_1B receptor appears to mediate the prosocial effects of entactogens acting as serotonin releasing agents like MDMA in animals.{{cite journal | vauthors = Nichols DE | title = Entactogens: How the Name for a Novel Class of Psychoactive Agents Originated | journal = Front Psychiatry | volume = 13 | issue = | pages = 863088 | date = 2022 | pmid = 35401275 | pmc = 8990025 | doi = 10.3389/fpsyt.2022.863088 | doi-access = free | url = }}{{cite journal | vauthors = Rein B, Raymond K, Boustani C, Tuy S, Zhang J, St Laurent R, Pomrenze MB, Boroon P, Heifets B, Smith M, Malenka RC | title = MDMA enhances empathy-like behaviors in mice via 5-HT release in the nucleus accumbens | journal = Sci Adv | volume = 10 | issue = 17 | pages = eadl6554 | date = April 2024 | pmid = 38657057 | pmc = 11042730 | doi = 10.1126/sciadv.adl6554 | bibcode = 2024SciA...10L6554R | url = }}{{cite journal | vauthors = Heifets BD, Salgado JS, Taylor MD, Hoerbelt P, Cardozo Pinto DF, Steinberg EE, Walsh JJ, Sze JY, Malenka RC | title = Distinct neural mechanisms for the prosocial and rewarding properties of MDMA | journal = Sci Transl Med | volume = 11 | issue = 522 | pages = | date = December 2019 | pmid = 31826983 | pmc = 7123941 | doi = 10.1126/scitranslmed.aaw6435 | url = }}{{cite journal | vauthors = Walsh JJ, Llorach P, Cardozo Pinto DF, Wenderski W, Christoffel DJ, Salgado JS, Heifets BD, Crabtree GR, Malenka RC | title = Systemic enhancement of serotonin signaling reverses social deficits in multiple mouse models for ASD | journal = Neuropsychopharmacology | volume = 46 | issue = 11 | pages = 2000–2010 | date = October 2021 | pmid = 34239048 | pmc = 8429585 | doi = 10.1038/s41386-021-01091-6 | url = }} In addition, serotonin 5-HT_1B receptor activation appears to mediate the locomotor hyperactivity of these agents.{{cite journal | vauthors = Martinez-Price D, Krebs-Thomson K, Geyer M | title=Behavioral Psychopharmacology of MDMA and MDMA-Like Drugs: A Review of Human and Animal Studies | journal=Addiction Research & Theory | publisher=Informa UK Limited | volume=10 | issue=1 | date=1 January 2002 | issn=1606-6359 | doi=10.1080/16066350290001704 | pages=43–67}}{{cite journal | vauthors = Rempel NL, Callaway CW, Geyer MA | title = Serotonin1B receptor activation mimics behavioral effects of presynaptic serotonin release | journal = Neuropsychopharmacology | volume = 8 | issue = 3 | pages = 201–211 | date = May 1993 | pmid = 8099482 | doi = 10.1038/npp.1993.22 | url = }}{{cite journal | vauthors = Scearce-Levie K, Viswanathan SS, Hen R | title = Locomotor response to MDMA is attenuated in knockout mice lacking the 5-HT1B receptor | journal = Psychopharmacology | location = Berlin | volume = 141 | issue = 2 | pages = 154–161 | date = January 1999 | pmid = 9952039 | doi = 10.1007/s002130050819 }} The serotonin 5-HT_1B receptor also appears to be required for the persisting antidepressant- and anxiolytic-like effects as well as acute hypolocomotion of the serotonergic psychedelic and non-selective serotonin receptor agonist psilocybin in animals.{{cite journal | vauthors = Fleury S, Nautiyal K | title = ACNP 63rd Annual Meeting: Poster Abstracts P609-P914: P691. The Non-Hallucinogenic Serotonin 1B Receptor is Necessary for the Persisting Behavioral Effects of Psilocybin in Mice | journal = Neuropsychopharmacology | volume = 49 | issue = Suppl 1 | pages = 418–594 (466) | date = December 2024 | pmid = 39643635 | doi = 10.1038/s41386-024-02013-y | url = | doi-access = free }}

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• 2ZEDMA (also a 5-HT_2A agonist)
• 5-Carboxamidotryptamine (5-CT)
• Almotriptan
• Anpirtoline (D-16949)
• Avitriptan
• Batoprazine
• CGS-12066A
• CP-93,129 (peripherally acting)
• CP-94,253
• CP-122,288 (mixed 5-HT_1B/1D agonist)
• CP-135,807 (mixed 5-HT_1B/1D agonist)
• Dihydroergotamine
• Donitriptan
• Eletriptan
• Eltoprazine (DU-28853)
• Emodin-8-glucoside
• Ergotamine
• Fluprazine
• Frovatriptan
• L-741,604
• Lisuride
• mCPP
• Methylergometrine (methylergonovine)
• Methysergide
• Naratriptan
• Oxymetazoline
• Pergolide
• PZKKN-94 (also a 5-HT₆ antagonist){{cite journal | vauthors = Zajdel P, Matłoka M, Konieczny J, Kos T, Lammers JC, Cavalco NG, Clark AA, Lenda T, Satała G, Canale V, Grychowska K, Krawczyk M, Nikiforuk A, Partyka A, Jastrzębska-Więsek M, Berghauzen-Maciejewska K, Biała D, Janicka M, Janusz A, Piast R, Mulewski K, Smuga D, Pieczykolan J, Wieczorek M, Moszczyński-Pętkowski R, Dubiel K, Ossowska K, Bojarski AJ, Kamiński K, McCorvy JD, Popik P | title = Simultaneous 5-HT1BR agonist/5-HT6R antagonist action as a potential treatment of Parkinson's disease and its comorbidities | journal = J Pharmacol Exp Ther | volume = 392 | issue = 2 | pages = 100055 | date = February 2025 | pmid = 40023605 | doi = 10.1016/j.jpet.2024.100055 | url = | doi-access = free }}
• Rizatriptan
• RU-24969 (mixed 5-HT_1A/1B agonist)
• (S)-DCPT
• Serotonin
• Sumatriptan
• TFMPP
• Tryptamine psychedelics (e.g., 5-MeO-DMT, DPT, psilocin/psilocybin)
• Zolmitriptan

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• Asenapine
• AZ10419369
• Bromocriptine
• Metergoline
• Naphthylpiperazine
• Vortioxetine
• Ziprasidone

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• Alprenolol
• AOP-208 (LB-208)
• AR-A000002 (AZD-8129){{cite journal | vauthors = Hudzik TJ, Yanek M, Porrey T, Evenden J, Paronis C, Mastrangelo M, Ryan C, Ross S, Stenfors C | title = Behavioral pharmacology of AR-A000002, a novel, selective 5-hydroxytryptamine(1B) antagonist | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 304 | issue = 3 | pages = 1072–84 | date = Mar 2003 | pmid = 12604684 | doi = 10.1124/jpet.102.045468 | s2cid = 20463714 }}
• Aripiprazole
• AZD-1134
• AZD-3783
• AZ12320927
• Carteolol
• Elzasonan
• GR-55562
• GR-127935
• Isamoltane (CGP-361A)
• LY-393558
• Metitepine (methiothepin)
• NAS-181 (MCOMM)
• Oxprenolol
• Penbutolol
• Propranolol
• Risperidone
• SB-216,641
• SB-224,289 (inverse agonist){{cite journal | vauthors = Selkirk JV, Scott C, Ho M, Burton MJ, Watson J, Gaster LM, Collin L, Jones BJ, Middlemiss DN, Price GW | title = SB-224289--a novel selective (human) 5-HT1B receptor antagonist with negative intrinsic activity | journal = British Journal of Pharmacology | volume = 125 | issue = 1 | pages = 202–8 | date = Sep 1998 | pmid = 9776361 | pmc = 1565605 | doi = 10.1038/sj.bjp.0702059 }}
• SB-236,057 (inverse agonist){{cite journal | vauthors = Roberts C, Watson J, Price GW, Middlemiss DN | title = SB-236057-A: a selective 5-HT1B receptor inverse agonist | journal = CNS Drug Reviews | volume = 7 | issue = 4 | pages = 433–44 | year = 2001 | pmid = 11830759 | doi = 10.1111/j.1527-3458.2001.tb00209.x | pmc = 6741665 }}
• SB-245,570
• SB-649,915
• Tertatolol
• Yohimbine

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• Dextromethorphan{{Cite journal|vauthors=Nguyen L, Thomas KL, Lucke-Wold BP, Cavendish JZ, Crowe MS, Matsumoto RR|year=2016|title=Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders|journal=Pharmacol. Ther.|volume=159|pages=1–22|pmid=26826604|doi=10.1016/j.pharmthera.2016.01.016}}

In humans the protein is coded by the gene HTR1B.

A genetic variant in the promoter region, A-161T, has been examined with respect to personality traits and showed no major effect.{{cite journal | vauthors = Tsai SJ, Wang YC, Chen JY, Hong CJ | title = Allelic variants of the tryptophan hydroxylase (A218C) and serotonin 1B receptor (A-161T) and personality traits | journal = Neuropsychobiology | volume = 48 | issue = 2 | pages = 68–71 | year = 2003 | pmid = 14504413 | doi = 10.1159/000072879 | s2cid = 42559772 }}

• 5-HT₁ receptor
• 5-HT receptor

{{reflist|33em}}

{{refbegin|33em}}

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{{refend}}

• {{cite web | url = http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=2 | title = 5-HT_1B | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology }}
• {{UCSC gene info|HTR1B}}
• {{PDBe-KB2|P28222|5-hydroxytryptamine receptor 1B}}

{{NLM content}}

{{G protein-coupled receptors}}

{{Serotonin receptor modulators}}

{{DEFAULTSORT:5-Ht1b Receptor}}

Category:Serotonin receptors

Category:Biology of attention deficit hyperactivity disorder