5-HT6 receptor: Wikis


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5-hydroxytryptamine (serotonin) receptor 6
Symbols HTR6; 5-HT6; 5-HT6R
External IDs OMIM601109 MGI1196627 HomoloGene673 IUPHAR: 5-HT6 GeneCards: HTR6 Gene
RNA expression pattern
PBB GE HTR6 206944 at tn.png
More reference expression data
Species Human Mouse
Entrez 3362 15565
Ensembl ENSG00000158748 ENSMUSG00000028747
UniProt P50406 Q14AW8
RefSeq (mRNA) NM_000871 NM_021358
RefSeq (protein) NP_000862 NP_067333
Location (UCSC) Chr 1:
19.86 - 19.88 Mb
Chr 4:
138.33 - 138.35 Mb
PubMed search [1] [2]

The 5-HT6 receptor, also known as the 5-hydroxytryptamine (serotonin) receptor 6 (HTR6), is a protein which in humans is encoded by the HTR6 gene.[1][2] The 5-HT6 receptor is primarily expressed in the brain and is involved in glutamatergic and cholinergic neuronal activity.[3] It is a potential target for drugs treating cognitive diseases, schizophrenia, anxiety and obesity.[4][5][6]



A large number of selective 5-HT6 ligands have now been developed and this is a productive current area of research.[7][8][9][10][11][12][13]


Full agonists

Partial Agonists



The receptor is encoded by the HTR6 gene. As the protein is a neuroreceptor it is possible that genetic variations in the gene would have an effect on brain, and research studies have investigated whether polymorphisms is associated with brain-related variables, such as neuropsychiatric disorders. For example, in 2004 one Chinese study reported an association between the C267T (rs1805054) polymorphism and Alzheimer's disease.[25] Others have studied the polymorphism in relation to Parkinson's disease.[26]

See also


  1. ^ "Entrez Gene: HTR6 5-hydroxytryptamine (serotonin) receptor 6". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3362. 
  2. ^ Kohen R, Metcalf MA, Khan N, Druck T, Huebner K, Lachowicz JE, Meltzer HY, Sibley DR, Roth BL, Hamblin MW (1996). "Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor". J. Neurochem. 66 (1): 47–56. doi:10.1046/j.1471-4159.1996.66010047.x (inactive 2010-01-04). PMID 8522988. 
  3. ^ Woolley ML, Marsden CA, Fone KC (2004). "5-HT6 receptors". Curr Drug Targets CNS Neurol Disord 3 (1): 59–79. doi:10.2174/1568007043482561. PMID 14965245. 
  4. ^ Holenz J, Pauwels PJ, Díaz JL, Mercè R, Codony X, Buschmann H (2006). "Medicinal chemistry strategies to 5-HT6 receptor ligands as potential cognitive enhancers and antiobesity agents". Drug Discov. Today 11 (7-8): 283–99. doi:10.1016/j.drudis.2006.02.004. PMID 16580970. 
  5. ^ Geldenhuys WJ, Van der Schyf CJ (2008). "Serotonin 5-HT6 receptor antagonists for the treatment of Alzheimer's disease". Curr Top Med Chem 8 (12): 1035–48. doi:10.2174/156802608785161420. PMID 18691131. http://www.bentham-direct.org/pages/content.php?CTMC/2008/00000008/00000012/0004R.SGM. 
  6. ^ Johnson CN, Ahmed M, Miller ND (September 2008). "5-HT6 receptor antagonists: prospects for the treatment of cognitive disorders including dementia". Curr Opin Drug Discov Devel 11 (5): 642–54. PMID 18729016. 
  7. ^ Trani G, Baddeley SM, Briggs MA, Chuang TT, Deeks NJ, Johnson CN, Khazragi AA, Mead TL, Medhurst AD, Milner PH, Quinn LP, Ray AM, Rivers DA, Stean TO, Stemp G, Trail BK, Witty DR (October 2008). "Tricyclic azepine derivatives as selective brain penetrant 5-HT6 receptor antagonists". Bioorg. Med. Chem. Lett. 18 (20): 5698–700. doi:10.1016/j.bmcl.2008.08.010. PMID 18793848. 
  8. ^ Liu KG, Lo JR, Comery TA, Zhang GM, Zhang JY, Kowal DM, Smith DL, Di L, Kerns EH, Schechter LE, Robichaud AJ (February 2009). "Identification of a series of benzoxazoles as potent 5-HT6 ligands". Bioorg. Med. Chem. Lett. 19 (4): 1115–7. doi:10.1016/j.bmcl.2008.12.107. PMID 19152787. 
  9. ^ Lee M, Rangisetty JB, Pullagurla MR, et al (2005). "1-(1-Naphthyl)piperazine as a novel template for 5-HT6 serotonin receptor ligands". Bioorg. Med. Chem. Lett. 15 (6): 1707–11. doi:10.1016/j.bmcl.2005.01.031. PMID 15745826. 
  10. ^ Sikazwe D, Bondarev ML, Dukat M, Rangisetty JB, Roth BL, Glennon RA (2006). "Binding of sulfonyl-containing arylalkylamines at human 5-HT6 serotonin receptors". J. Med. Chem. 49 (17): 5217–25. doi:10.1021/jm060469q. PMID 16913710. 
  11. ^ Zhou P, Yan Y, Bernotas R, et al (2005). "4-(2-Aminoethoxy)-N-(phenylsulfonyl)indoles as novel 5-HT6 receptor ligands". Bioorg. Med. Chem. Lett. 15 (5): 1393–6. doi:10.1016/j.bmcl.2005.01.005. PMID 15713394. 
  12. ^ Ahmed M, Briggs MA, Bromidge SM, et al (2005). "Bicyclic heteroarylpiperazines as selective brain penetrant 5-HT6 receptor antagonists". Bioorg. Med. Chem. Lett. 15 (21): 4867–71. doi:10.1016/j.bmcl.2005.06.107. PMID 16143522. 
  13. ^ Alcalde E, Mesquida N, Frigola J, López-Pérez S, Mercè R (October 2008). "Indene-based scaffolds. Design and synthesis of novel serotonin 5-HT6 receptor ligands". Org. Biomol. Chem. 6 (20): 3795–810. doi:10.1039/b808641a. PMID 18843410. 
  14. ^ Mattsson C, Sonesson C, Sandahl A, Greiner HE, Gassen M, Plaschke J, Leibrock J, Böttcher H (October 2005). "2-Alkyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoles as novel 5-HT6 receptor agonists". Bioorg. Med. Chem. Lett. 15 (19): 4230–4. doi:10.1016/j.bmcl.2005.06.067. PMID 16055331. 
  15. ^ Glennon RA, Lee M, Rangisetty JB, Dukat M, Roth BL, Savage JE, McBride A, Rauser L, Hufeisen S, Lee DK (2000). "2-Substituted tryptamines: agents with selectivity for 5-HT6 serotonin receptors". J. Med. Chem. 43 (5): 1011–8. doi:10.1021/jm990550b. PMID 10715164. 
  16. ^ Schechter LE, Lin Q, Smith DL, Zhang G, Shan Q, Platt B, Brandt MR, Dawson LA, Cole D, Bernotas R, Robichaud A, Rosenzweig-Lipson S, Beyer CE (May 2008). "Neuropharmacological profile of novel and selective 5-HT6 receptor agonists: WAY-181187 and WAY-208466". Neuropsychopharmacology 33 (6): 1323–35. doi:10.1038/sj.npp.1301503. PMID 17625499. 
  17. ^ Cole DC, Stock JR, Lennox WJ, Bernotas RC, Ellingboe JW, Boikess S, Coupet J, Smith DL, Leung L, Zhang GM, Feng X, Kelly MF, Galante R, Huang P, Dawson LA, Marquis K, Rosenzweig-Lipson S, Beyer CE, Schechter LE (November 2007). "Discovery of N1-(6-chloroimidazo[2,1-b][1,3]thiazole-5-sulfonyl)tryptamine as a potent, selective, and orally active 5-HT(6) receptor agonist". Journal of Medicinal Chemistry 50 (23): 5535–8. doi:10.1021/jm070521y. PMID 17948978. 
  18. ^ Alcalde E, Mesquida N, López-Pérez S, Frigola J, Mercè R (2009). "Indene-based scaffolds. 2. An indole-indene switch: discovery of novel indenylsulfonamides as 5-HT6 serotonin receptor agonists". J. Med. Chem. 52 (3): 675–87. doi:10.1021/jm8009469. PMID 19159187. 
  19. ^ Romero G, Sánchez E, Pujol M, Pérez P, Codony X, Holenz J, Buschmann H, Pauwels PJ (August 2006). "Efficacy of selective 5-HT6 receptor ligands determined by monitoring 5-HT6 receptor-mediated cAMP signaling pathways". Br. J. Pharmacol. 148 (8): 1133–43. doi:10.1038/sj.bjp.0706827. PMID 16865095. 
  20. ^ Fisas A, Codony X, Romero G, Dordal A, Giraldo J, Mercé R, Holenz J, Vrang N, Sørensen RV, Heal D, Buschmann H, Pauwels PJ (August 2006). "Chronic 5-HT6 receptor modulation by E-6837 induces hypophagia and sustained weight loss in diet-induced obese rats". Br. J. Pharmacol. 148 (7): 973–83. doi:10.1038/sj.bjp.0706807. PMID 16783408. 
  21. ^ Hugerth A, Brisander M, Wrange U, Kritikos M, Norrlind B, Svensson M, Bisrat M, Ostelius J (February 2006). "Physical characterization of anhydrous and hydrous forms of the hydrochloride salt of BVT.5182 a novel 5-HT6 receptor antagonist". Drug Dev Ind Pharm 32 (2): 185–96. doi:10.1080/03639040500466122. PMID 16537199. 
  22. ^ Heal DJ, Smith SL, Fisas A, Codony X, Buschmann H (February 2008). "Selective 5-HT6 receptor ligands: progress in the development of a novel pharmacological approach to the treatment of obesity and related metabolic disorders". Pharmacol. Ther. 117 (2): 207–31. doi:10.1016/j.pharmthera.2007.08.006. PMID 18068807. 
  23. ^ Wu J, Li Q, Bezprozvanny I. Evaluation of Dimebon in cellular model of Huntington's disease. Molecular Neurodegeneration. 2008 Oct 21;3-15. PMID 18939977
  24. ^ Ivachtchenko AV, Frolov EB, Mitkin OD, Kysil VM, Khvat AV, Okun IM, Tkachenko SE (June 2009). "Synthesis and biological evaluation of novel gamma-carboline analogues of Dimebon as potent 5-HT6 receptor antagonists". Bioorganic & Medicinal Chemistry Letters 19 (12): 3183–7. doi:10.1016/j.bmcl.2009.04.128. PMID 19443217. 
  25. ^ Kan R, Wang B, Zhang C, Yang Z, Ji S, Lu Z, Zheng C, Jin F, Wang L (November 2004). "Association of the HTR6 polymorphism C267T with late-onset Alzheimer's disease in Chinese". Neurosci. Lett. 372 (1-2): 27–9. doi:10.1016/j.neulet.2004.09.007. PMID 15531082. 
  26. ^ Messina D, Annesi G, Serra P, Nicoletti G, Pasqua A, Annesi F, Tomaino C, Cirò-Candiano IC, Carrideo S, Caracciolo M, Spadafora P, Zappia M, Savettieri G, Quattrone A (12 March 2002). "Association of the 5-HT6 receptor gene polymorphism C267T with Parkinson's disease". Neurology 58 (5): 828–9. PMID 11889255. http://www.neurology.org/cgi/content/citation/58/5/828. 

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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