Biology:5-HT1B receptor
 Generic protein structure example |
5-hydroxytryptamine receptor 1B also known as the 5-HT1B receptor is a protein that in humans is encoded by the HTR1B gene.[1][2] The 5-HT1B receptor is a 5-HT receptor subtype.[3]
Tissue distribution and function
5-HT1B receptors are widely distributed throughout the central nervous system with the highest concentrations found in the frontal cortex, basal ganglia, striatum, and the hippocampus.[4] The function of the 5-HT1B 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[5] and decreasing glutamatergic transmission by reducing miniature excitatory postsynaptic potential (mEPSP) frequency,[6] respectively. In the hippocampus, a recent study has demonstrated that activation of postsynaptic 5-HT1B heteroreceptors produces a facilitation in excitatory synaptic transmission which is altered in depression.[7] When the expression of 5-HT1B 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-HT1E.[8]
Outside of the CNS, the 5-HT1B receptor is also expressed on the endothelium of blood vessels, particularly in the meninges.[9] Activation of these receptors results in vasoconstriction. The high distribution of vasoconstrictive 5-HT1B and 5-HT1D receptors around the brain makes them a valuable drug target for the treatment of migraines.[9]
Blocking 5-HT1B receptor signalling also increases the number of osteoblasts, bone mass, and the bone formation rate.[10]
Knockout mice lacking the 5-HT1B gene have been reported to have a higher preference for alcohol, although later studies failed to replicate such abnormalities in alcohol consumption.[11] 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.[11]
Activation of the serotonin 5-HT1B receptor appears to mediate the prosocial effects of entactogens acting as serotonin releasing agents like MDMA in animals.[12][13][14][15] In addition, serotonin 5-HT1B receptor activation appears to mediate the locomotor hyperactivity of these agents.[16][17][18] The serotonin 5-HT1B 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.[19]
Ligands
Agonists
- 2ZEDMA (also a 5-HT2A agonist)
- 5-Carboxamidotryptamine (5-CT)
- 5-MAPB[20]
- 5-MAPBT[21]
- 6-MAPB[20]
- 6-MAPBT[21]
- Almotriptan
- Anpirtoline (D-16949)
- Avitriptan
- Batoprazine
- BK-5-MAPB[20]
- BK-5-MAPBT[21]
- BK-6-MAPB[20]
- CGS-12066 (CGS-12066A, CGS-12066B)
- CP-93,129
- CP-94,253
- CP-122,288 (mixed 5-HT1B/1D agonist)
- CP-135,807 (mixed 5-HT1B/1D agonist)
- Dihydroergotamine
- Donitriptan
- Eletriptan
- Eltoprazine (DU-28853)
- Emodin-8-glucoside
- Ergotamine
- Fluprazine
- Frovatriptan
- L-741604
- Lisuride
- mCPP
- MDMA[22]
- Methylergometrine (methylergonovine)
- Methylone[22]
- Methysergide
- Naratriptan
- Oxymetazoline
- Pergolide
- PGI-7043
- PZKKN-94 (also a 5-HT6 antagonist)[23]
- Rizatriptan
- RU-24969 (mixed 5-HT1A/1B agonist)
- (S)-DCPT
- Serotonin
- Sumatriptan
- TFMPP
- Tryptamine psychedelics (e.g., 5-MeO-DMT, DPT, psilocin/psilocybin)
- Zolmitriptan
Partial agonists
Antagonists and inverse agonists
- Alprenolol
- AOP-208 (LB-208)
- AR-A000002 (AZD-8129)[24]
- Aripiprazole
- AZD-1134
- AZD-3783
- AZ12320927
- Carteolol
- Elzasonan
- F-14258
- 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)[25]
- SB-236,057 (inverse agonist)[26]
- SB-245,570
- SB-616234
- SB-649,915
- Tertatolol
- Yohimbine
Negative allosteric modulators
- 5-HT-moduline
Unknown
Genetics
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.[28]
See also
References
- ↑ "Characterization of the human 5-hydroxytryptamine1B receptor". The Journal of Biological Chemistry 267 (9): 5735–8. Mar 1992. doi:10.1016/S0021-9258(18)42612-9. PMID 1348246.
- ↑ "Genetic diversity of the human serotonin receptor 1B (HTR1B) gene". Genomics 72 (1): 1–14. Feb 2001. doi:10.1006/geno.2000.6411. PMID 11247661.
- ↑ "Entrez Gene: HTR1B 5-hydroxytryptamine (serotonin) receptor 1B". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=3351.
- ↑ "5-hydroxytryptamine (serotonin) receptor 1B, G protein-coupled". https://www.genecards.org/cgi-bin/carddisp.pl?gene=HTR1B.
- ↑ "Serotonin receptors - from molecular biology to clinical applications". Physiological Research 60 (1): 15–25. 2011. doi:10.33549/physiolres.931903. PMID 20945968.
- ↑ "A single in vivo cocaine administration impairs 5-HT(1B) receptor-induced long-term depression in the nucleus accumbens". Journal of Neurochemistry 125 (6): 809–21. Jun 2013. doi:10.1111/jnc.12227. PMID 23452061.
- ↑ "Local potentiation of excitatory synapses by serotonin and its alteration in rodent models of depression". Nature Neuroscience 16 (4): 464–72. Apr 2013. doi:10.1038/nn.3355. PMID 23502536.
- ↑ "Transitions in the transcriptome of the serotonergic and dopaminergic systems in the human brain during adolescence". European Neuropsychopharmacology 24 (7): 1123–32. Jul 2014. doi:10.1016/j.euroneuro.2014.02.009. PMID 24721318.
- ↑ 9.0 9.1 "Mechanisms of action of the 5-HT1B/1D receptor agonists". Archives of Neurology 59 (7): 1084–1088. July 2002. doi:10.1001/archneur.59.7.1084. PMID 12117355.
- ↑ "Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum". Cell 135 (5): 825–37. Nov 2008. doi:10.1016/j.cell.2008.09.059. PMID 19041748.
- Lay summary in: Michael Smith. "Serotonin in Gut Linked to Bone Formation". http://www.medpagetoday.com/Endocrinology/Osteoporosis/11923.
- ↑ 11.0 11.1 "Molecular, pharmacological and functional diversity of 5-HT receptors". Pharmacology Biochemistry and Behavior 71 (4): 533–54. Apr 2002. doi:10.1016/S0091-3057(01)00746-8. PMID 11888546.
- ↑ "Entactogens: How the Name for a Novel Class of Psychoactive Agents Originated". Front Psychiatry 13. 2022. doi:10.3389/fpsyt.2022.863088. PMID 35401275.
- ↑ "MDMA enhances empathy-like behaviors in mice via 5-HT release in the nucleus accumbens". Sci Adv 10 (17). April 2024. doi:10.1126/sciadv.adl6554. PMID 38657057. Bibcode: 2024SciA...10L6554R.
- ↑ "Distinct neural mechanisms for the prosocial and rewarding properties of MDMA". Sci Transl Med 11 (522). December 2019. doi:10.1126/scitranslmed.aaw6435. PMID 31826983.
- ↑ "Systemic enhancement of serotonin signaling reverses social deficits in multiple mouse models for ASD". Neuropsychopharmacology 46 (11): 2000–2010. October 2021. doi:10.1038/s41386-021-01091-6. PMID 34239048.
- ↑ "Behavioral Psychopharmacology of MDMA and MDMA-Like Drugs: A Review of Human and Animal Studies". Addiction Research & Theory (Informa UK Limited) 10 (1): 43–67. 1 January 2002. doi:10.1080/16066350290001704. ISSN 1606-6359.
- ↑ "Serotonin1B receptor activation mimics behavioral effects of presynaptic serotonin release". Neuropsychopharmacology 8 (3): 201–211. May 1993. doi:10.1038/npp.1993.22. PMID 8099482.
- ↑ "Locomotor response to MDMA is attenuated in knockout mice lacking the 5-HT1B receptor". Psychopharmacology (Berlin) 141 (2): 154–161. January 1999. doi:10.1007/s002130050819. PMID 9952039.
- ↑ "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". Neuropsychopharmacology 49 (Suppl 1): 418–594 (466). December 2024. doi:10.1038/s41386-024-02013-y. PMID 39643635.
- ↑ 20.0 20.1 20.2 20.3 Matthew Baggott, "Advantageous benzofuran compositions for mental disorders or enhancement", US patent 20230150963, published 2023 May 18, assigned to Tactogen
- ↑ 21.0 21.1 21.2 Baggott M, "Advantageous benzothiophene compositions for mental disorders or enhancement.", WO patent 2022/010937, published 13 January 2022
- ↑ 22.0 22.1 "The polypharmacology of psychedelics reveals multiple targets for potential therapeutics". Neuron 113 (19): 3129–3142.e9. July 2025. doi:10.1016/j.neuron.2025.06.012. PMID 40683247. https://www.cell.com/cms/10.1016/j.neuron.2025.06.012/attachment/7d8365fe-51f3-4a28-bf40-9999bec837f6/mmc11.pdf.
- ↑ "Simultaneous 5-HT1BR agonist/5-HT6R antagonist action as a potential treatment of Parkinson's disease and its comorbidities". J Pharmacol Exp Ther 392 (2). February 2025. doi:10.1016/j.jpet.2024.100055. PMID 40023605.
- ↑ "Behavioral pharmacology of AR-A000002, a novel, selective 5-hydroxytryptamine(1B) antagonist". The Journal of Pharmacology and Experimental Therapeutics 304 (3): 1072–84. Mar 2003. doi:10.1124/jpet.102.045468. PMID 12604684.
- ↑ "SB-224289--a novel selective (human) 5-HT1B receptor antagonist with negative intrinsic activity". British Journal of Pharmacology 125 (1): 202–8. Sep 1998. doi:10.1038/sj.bjp.0702059. PMID 9776361.
- ↑ "SB-236057-A: a selective 5-HT1B receptor inverse agonist". CNS Drug Reviews 7 (4): 433–44. 2001. doi:10.1111/j.1527-3458.2001.tb00209.x. PMID 11830759.
- ↑ "Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders". Pharmacol. Ther. 159: 1–22. 2016. doi:10.1016/j.pharmthera.2016.01.016. PMID 26826604.
- ↑ "Allelic variants of the tryptophan hydroxylase (A218C) and serotonin 1B receptor (A-161T) and personality traits". Neuropsychobiology 48 (2): 68–71. 2003. doi:10.1159/000072879. PMID 14504413.
Further reading
- "5-HT1B receptors and aggression: a review". European Journal of Pharmacology 526 (1–3): 207–17. Dec 2005. doi:10.1016/j.ejphar.2005.09.066. PMID 16310769.
- "Molecular cloning and functional characterization of a human 5-HT1B serotonin receptor: a homologue of the rat 5-HT1B receptor with 5-HT1D-like pharmacological specificity". Biochemical and Biophysical Research Communications 184 (2): 752–9. Apr 1992. doi:10.1016/0006-291X(92)90654-4. PMID 1315531.
- "Cloning and pharmacological characterization of a novel human 5-hydroxytryptamine1D receptor subtype". Molecular Pharmacology 42 (3): 439–44. Sep 1992. PMID 1328844.
- "A human serotonin 1D receptor variant (5HT1D beta) encoded by an intronless gene on chromosome 6". Proceedings of the National Academy of Sciences of the United States of America 89 (12): 5522–6. Jun 1992. doi:10.1073/pnas.89.12.5522. PMID 1351684. Bibcode: 1992PNAS...89.5522D.
- "Molecular cloning of a human serotonin receptor (S12) with a pharmacological profile resembling that of the 5-HT1D subtype". The Journal of Biological Chemistry 267 (11): 7553–62. Apr 1992. doi:10.1016/S0021-9258(18)42552-5. PMID 1559993.
- "Human serotonin 1D receptor is encoded by a subfamily of two distinct genes: 5-HT1D alpha and 5-HT1D beta". Proceedings of the National Academy of Sciences of the United States of America 89 (8): 3630–4. Apr 1992. doi:10.1073/pnas.89.8.3630. PMID 1565658. Bibcode: 1992PNAS...89.3630W.
- "Cloning and expression of the human 5-HT1B-type receptor gene". Biochemical and Biophysical Research Communications 185 (2): 517–23. Jun 1992. doi:10.1016/0006-291X(92)91655-A. PMID 1610347.
- "Identification of genetic variation in the human serotonin 1D beta receptor gene". Biochemical and Biophysical Research Communications 205 (2): 1194–200. Dec 1994. doi:10.1006/bbrc.1994.2792. PMID 7802650.
- "Human serotonin1B receptor expression in Sf9 cells: phosphorylation, palmitoylation, and adenylyl cyclase inhibition". Biochemistry 32 (43): 11727–33. Nov 1993. doi:10.1021/bi00094a032. PMID 8218242.
- "Differential expression of sumatriptan-sensitive 5-hydroxytryptamine receptors in human trigeminal ganglia and cerebral blood vessels". Molecular Pharmacology 50 (2): 219–23. Aug 1996. PMID 8700126.
- "Autoradiographic mapping of 5-HT(1B) and 5-HT(1D) receptors in the post mortem human brain using [(3)H]GR 125743". Brain Research 915 (1): 47–57. Oct 2001. doi:10.1016/S0006-8993(01)02823-2. PMID 11578619.
- "Oligomerization of G-protein-coupled receptors shown by selective co-immunoprecipitation". The Journal of Biological Chemistry 277 (18): 15482–5. May 2002. doi:10.1074/jbc.M201539200. PMID 11854302.
- "Association of a polymorphism of the serotonin 1B receptor gene and alcohol dependence with inactive aldehyde dehydrogenase-2". Journal of Neural Transmission 109 (4): 513–21. Apr 2002. doi:10.1007/s007020200042. PMID 11956970.
- "Serotonergic system and attention deficit hyperactivity disorder (ADHD): a potential susceptibility locus at the 5-HT(1B) receptor gene in 273 nuclear families from a multi-centre sample". Molecular Psychiatry 7 (7): 718–25. 2003. doi:10.1038/sj.mp.4001048. PMID 12192616.
- "Substance abuse disorder and major depression are associated with the human 5-HT1B receptor gene (HTR1B) G861C polymorphism". Neuropsychopharmacology 28 (1): 163–9. Jan 2003. doi:10.1038/sj.npp.1300000. PMID 12496953.
- "The serotonin 5-HT1B receptor gene and attention deficit hyperactivity disorder". Molecular Psychiatry 8 (1): 98–102. Jan 2003. doi:10.1038/sj.mp.4001244. PMID 12556913.
- "Linkage disequilibrium and haplotype analysis between serotonin receptor 1B gene variations and subtypes of alcoholism". American Journal of Medical Genetics Part B 121B (1): 83–8. Aug 2003. doi:10.1002/ajmg.b.20064. PMID 12898580.
External links
- "5-HT1B". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=2.
- Human HTR1B genome location and HTR1B gene details page in the UCSC Genome Browser.
- Overview of all the structural information available in the PDB for UniProt: P28222 (5-hydroxytryptamine receptor 1B) at the PDBe-KB.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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