5-HT6 receptor

The 5-HT₆ receptor, also known as the 5-hydroxytryptamine (serotonin) receptor 6 (HTR6), is a human gene.cite web | title = Entrez Gene: HTR6 5-hydroxytryptamine (serotonin) receptor 6| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3362| accessdate = ] cite journal | author = Kohen R, Metcalf MA, Khan N, Druck T, Huebner K, Lachowicz JE, Meltzer HY, Sibley DR, Roth BL, Hamblin MW | title = Cloning, characterization, and chromosomal localization of a human 5-HT₆ serotonin receptor | journal = J. Neurochem. | volume = 66 | issue = 1 | pages = 47–56 | year = 1996 | pmid = 8522988 | doi = 10.1046/j.1471-4159.1996.66010047.x | issn = ] The 5-HT₆ receptor is primarily expressed in the brain and is involved in glutamatergic and cholinergic neuronal activity.cite journal | author = Woolley ML, Marsden CA, Fone KC | title = 5-HT₆ receptors | journal = Curr Drug Targets CNS Neurol Disord | volume = 3 | issue = 1 | pages = 59–79 | year = 2004 | pmid = 14965245 | doi = | issn = ] It is a potential target for drugs treating cognitive diseases, schizophrenia, anxiety and obesity.cite journal | author = Holenz J, Pauwels PJ, Díaz JL, Mercè R, Codony X, Buschmann H | title = Medicinal chemistry strategies to 5-HT₆ receptor ligands as potential cognitive enhancers and antiobesity agents | journal = Drug Discov. Today | volume = 11 | issue = 7-8 | pages = 283–99 | year = 2006 | pmid = 16580970 | doi = 10.1016/j.drudis.2006.02.004 | issn = ]

Ligands

Full agonists

Agonists for the 5-HT₆ receptor include:
* 2-ethyl-5-methoxy-N,N-dimethyltryptamine (EMDT)cite journal | author = Glennon RA, Lee M, Rangisetty JB, Dukat M, Roth BL, Savage JE, McBride A, Rauser L, Hufeisen S, Lee DK | title = 2-Substituted tryptamines: agents with selectivity for 5-HT₆ serotonin receptors | journal = J. Med. Chem. | volume = 43 | issue = 5 | pages = 1011–8 | year = 2000 | pmid = 10715164 | doi = 10.1021/jm990550b | issn = ]
* arylsulfonyl-tryptaminescite journal | author = 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 | title = Discovery of N1-(6-chloroimidazo [2,1-b] [1,3] thiazole-5-sulfonyl)tryptamine as a potent, selective, and orally active 5-HT₆ receptor agonist | journal = J. Med. Chem. | volume = 50 | issue = 23 | pages = 5535–8 | year = 2007 | pmid = 17948978 | doi = 10.1021/jm070521y | issn = ]
* arylsulfonyl-heterocycles.cite journal | author = Elokdah H, Li D, McFarlane G, Bernotas RC, Robichaud AJ, Magolda RL, Zhang GM, Smith D, Schechter LE | title = Novel 1-(azacyclyl)-3-arylsulfonyl-1H-pyrrolo [2,3-b] pyridines as 5-HT₆ agonists and antagonists | journal = Bioorg. Med. Chem. | volume = 15 | issue = 18 | pages = 6208–26 | year = 2007 | pmid = 17624788 | doi = 10.1016/j.bmc.2007.06.024 | issn = ]
*EMD-386,088 (5-Chloro-2-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H -indole) - potent and selective 5HT₆ agonist (EC₅₀ 1nM)cite journal | author = Mattsson C, Sonesson C, Sandahl A, Greiner HE, Gassen M, Plaschke J, Leibrock J, Böttcher H | title = 2-Alkyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoles as novel 5-HT6 receptor agonists | journal = Bioorg. Med. Chem. Lett. | volume = 15 | issue = 19 | pages = 4230–4 | year = 2005 | month = October | pmid = 16055331 | doi = 10.1016/j.bmcl.2005.06.067 | url = | issn = ]
*WAY-181,187
*WAY-208,466

Antagonists

*SB-258,585 (4-Iodo-N- [4-methoxy-3-(4-methyl-1-piperazinyl)phenyl] benzenesulfonamide)
*SB-399,885

Genetics

The receptor is coded 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.cite journal | author = Kan R, Wang B, Zhang C, Yang Z, Ji S, Lu Z, Zheng C, Jin F, Wang L | title = Association of the HTR6 polymorphism C267T with late-onset Alzheimer's disease in Chinese | journal = Neurosci. Lett. | volume = 372 | issue = 1-2 | pages = 27–9 | year = 2004 | month = November | pmid = 15531082 | doi = 10.1016/j.neulet.2004.09.007 | url = | issn = ] Others have studied the polymorphism in relation to Parkinson's disease.cite journal | author = 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 | title = Association of the 5-HT6 receptor gene polymorphism C267T with Parkinson's disease | journal = Neurology | volume = 58 | issue = 5 | pages = 828–9 | year = 2002 | month = March | pmid = 11889255 | url = http://www.neurology.org/cgi/content/citation/58/5/828 | issn = ]

ee also

* 5-HT receptor

References

Further reading

PBB_Further_reading
citations =
*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 |year= 2002 |pmid= 11888546 |doi=
*cite journal | author=Raymond JR, Mukhin YV, Gelasco A, "et al." |title=Multiplicity of mechanisms of serotonin receptor signal transduction. |journal=Pharmacol. Ther. |volume=92 |issue= 2-3 |pages= 179–212 |year= 2002 |pmid= 11916537 |doi=
*cite journal | author=Van Oekelen D, Luyten WH, Leysen JE |title=5-HT2A and 5-HT2C receptors and their atypical regulation properties. |journal=Life Sci. |volume=72 |issue= 22 |pages= 2429–49 |year= 2003 |pmid= 12650852 |doi=
*cite journal | author=Dubertret C, Hanoun N, Adès J, "et al." |title=Family-based association study of the serotonin-6 receptor gene (C267T polymorphism) in schizophrenia. |journal=Am. J. Med. Genet. B Neuropsychiatr. Genet. |volume=126 |issue= 1 |pages= 10–5 |year= 2004 |pmid= 15048641 |doi= 10.1002/ajmg.b.20120
*cite journal | author=Ullmer C, Schmuck K, Kalkman HO, Lübbert H |title=Expression of serotonin receptor mRNAs in blood vessels. |journal=FEBS Lett. |volume=370 |issue= 3 |pages= 215–21 |year= 1995 |pmid= 7656980 |doi=
*cite journal | author=Kohen R, Metcalf MA, Khan N, "et al." |title=Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor. |journal=J. Neurochem. |volume=66 |issue= 1 |pages= 47–56 |year= 1996 |pmid= 8522988 |doi=
*cite journal | author=Orlacchio A, Kawarai T, Paciotti E, "et al." |title=Association study of the 5-hydroxytryptamine(6) receptor gene in Alzheimer's disease. |journal=Neurosci. Lett. |volume=325 |issue= 1 |pages= 13–6 |year= 2002 |pmid= 12023056 |doi=
*cite journal | author=Strausberg RL, Feingold EA, Grouse LH, "et al." |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899
*cite journal | author=Ham BJ, Kim YH, Choi MJ, "et al." |title=Serotonergic genes and personality traits in the Korean population. |journal=Neurosci. Lett. |volume=354 |issue= 1 |pages= 2–5 |year= 2004 |pmid= 14698468 |doi=
*cite journal | author=Bernotas R, Lenicek S, Antane S, "et al." |title=1-(2-Aminoethyl)-3-(arylsulfonyl)-1H-indoles as novel 5-HT6 receptor ligands. |journal=Bioorg. Med. Chem. Lett. |volume=14 |issue= 22 |pages= 5499–502 |year= 2005 |pmid= 15482912 |doi= 10.1016/j.bmcl.2004.09.003
*cite journal | author=Gerhard DS, Wagner L, Feingold EA, "et al." |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504
*cite journal | author=Kang H, Lee WK, Choi YH, "et al." |title=Molecular analysis of the interaction between the intracellular loops of the human serotonin receptor type 6 (5-HT6) and the alpha subunit of GS protein. |journal=Biochem. Biophys. Res. Commun. |volume=329 |issue= 2 |pages= 684–92 |year= 2005 |pmid= 15737640 |doi= 10.1016/j.bbrc.2005.02.040
*cite journal | author=Tao WA, Wollscheid B, O'Brien R, "et al." |title=Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry. |journal=Nat. Methods |volume=2 |issue= 8 |pages= 591–8 |year= 2005 |pmid= 16094384 |doi= 10.1038/nmeth776
*cite journal | author=Lorke DE, Lu G, Cho E, Yew DT |title=Serotonin 5-HT2A and 5-HT6 receptors in the prefrontal cortex of Alzheimer and normal aging patients. |journal=BMC neuroscience |volume=7 |issue= |pages= 36 |year= 2006 |pmid= 16640790 |doi= 10.1186/1471-2202-7-36
*cite journal | author=Yun HM, Kim S, Kim HJ, "et al." |title=The novel cellular mechanism of human 5-HT6 receptor through an interaction with Fyn. |journal=J. Biol. Chem. |volume=282 |issue= 8 |pages= 5496–505 |year= 2007 |pmid= 17189269 |doi= 10.1074/jbc.M606215200

External links

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