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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/07/26 17:37:33」(JST)

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The 5-HT₆ receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin (5-hydroxytryptamine, 5-HT).^[1] It is a G protein-coupled receptor (GPCR) that is coupled to G_s and mediates excitatory neurotransmission.^[1] HTR6 denotes the human gene encoding for the receptor.^[2]

Distribution

The 5-HT₆ receptor is expressed almost exclusively in the brain.^[3] It is distributed in various areas including, but not limited to, the olfactory tubercle, cerebral cortex (frontal and entorhinal regions), nucleus accumbens, striatum, caudate nucleus, hippocampus, and the molecular layer of the cerebellum.^[1]^[4]^[5] Based on its abundance in extrapyramidal, limbic, and cortical regions it can be suggested that the 5-HT₆ receptor plays a role in functions like motor control, emotionality, cognition, and memory.^[3]^[5]^[6]

Function

Blockade of central 5-HT₆ receptors has been shown to increase glutamatergic and cholinergic neurotransmission in various brain areas,^[7]^[8]^[9]^[10] whereas activation enhances GABAergic signaling in a widespread manner.^[11] Antagonism of 5-HT₆ receptors also facilitates dopamine and norepinephrine release in the frontal cortex,^[10]^[12] while stimulation has the opposite effect.^[11]

Despite the 5-HT₆ receptor having a functionally excitatory action, it is largely co-localized with GABAergic neurons and therefore produces an overall inhibition of brain activity.^[11] In parallel with this, 5-HT₆ antagonists improve cognition, learning, and memory,^[13] and agents such as latrepirdine, Lu AE58054, and SB-742,457 are being developed as novel treatments for Alzheimer's disease and other forms of dementia.^[10]^[14]^[15] 5-HT₆ antagonists have also been shown to reduce appetite and produce weight loss, and as a result, PRX-07034, BVT-5,182, and BVT-74,316 are being investigated for the treatment of obesity.^[16]^[17]

Recently, the 5-HT₆ agonists WAY-181,187 and WAY-208,466 have been demonstrated to be active in rodent models of depression, anxiety, and obsessive-compulsive disorder (OCD), and such agents may be useful treatments for these conditions.^[11]^[18] Additionally, it can be inferred that 5-HT₆ activation likely plays a major role in the therapeutic benefits of serotonergic antidepressants like the selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs).

Ligands

A large number of selective 5-HT₆ ligands have now been developed and this is a productive current area of research.^[19]^[20]^[21]^[22]^[23]^[24]^[25]

Full agonists

EMD-386,088 - potent and selective 5HT₆ agonist (EC₅₀ 1nM)^[26]
2-Ethyl-5-methoxy-N,N-dimethyltryptamine (EMDT)^[27]
WAY-181,187^[11]
WAY-208,466^[11]
N1-(6-chloroimidazo[2,1-b][1,3]thiazole-5-sulfonyl)tryptamine (compound 11q)^[28]
N-(inden-5-yl)imidazothiazole-5-sulfonamide (43): K_i = 4.5nM, EC₅₀ = 0.9nM, E_max = 98%^[29]
E-6837 - Full agonist at human 5-HT₆ receptors

Partial Agonists

E-6801^[30]
E-6837 - partial agonist at rat 5-HT₆ receptors. Orally active in rats, and caused weight loss with chronic administration^[31]

Antagonists

BVT-5182^[32]
BVT-74316^[16]
Cerlapirdine
EGIS-12233 - mixed 5-HT₆ / 5-HT₇ antagonist
Latrepirdine (non-selective)^[33] and analogues^[34]
Lu AE58054
MS-245
PRX-07034
SB-258,585
SB-271,046
SB-357,134
SB-399,885
SB-742,457
Ro04-6790
Atypical antipsychotics (olanzapine, asenapine, clozapine)
WAY-255315 / SAM-315: Ki = 1.1nM, IC = 13nM^[35]

Genetics

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.^[36] Others have studied the polymorphism in relation to Parkinson's disease.^[37]

References

^ ^a ^b ^c 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. PMID 8522988.
^ "Entrez Gene: HTR6 5-hydroxytryptamine (serotonin) receptor 6".
^ ^a ^b Woolley ML, Marsden CA, Fone KC (February 2004). "5-ht6 receptors". Current Drug Targets. CNS and Neurological Disorders 3 (1): 59–79. doi:10.2174/1568007043482561. PMID 14965245.
^ Ruat M, Traiffort E, Arrang JM, et al. (May 1993). "A novel rat serotonin (5-HT6) receptor: molecular cloning, localization and stimulation of cAMP accumulation". Biochemical and Biophysical Research Communications 193 (1): 268–76. doi:10.1006/bbrc.1993.1619. PMID 8389146.
^ ^a ^b Gérard C, Martres MP, Lefèvre K, et al. (January 1997). "Immuno-localization of serotonin 5-HT6 receptor-like material in the rat central nervous system". Brain Research 746 (1-2): 207–19. doi:10.1016/S0006-8993(96)01224-3. PMID 9037500.
^ Hamon M, Doucet E, Lefèvre K, et al. (August 1999). "Antibodies and antisense oligonucleotide for probing the distribution and putative functions of central 5-HT6 receptors". Neuropsychopharmacology 21 (2 Suppl): 68S–76S. doi:10.1016/S0893-133X(99)00044-5. PMID 10432491.
^ Dawson LA, Nguyen HQ, Li P (May 2000). "In vivo effects of the 5-HT(6) antagonist SB-271046 on striatal and frontal cortex extracellular concentrations of noradrenaline, dopamine, 5-HT, glutamate and aspartate". British Journal of Pharmacology 130 (1): 23–6. doi:10.1038/sj.bjp.0703288. PMC 1572041. PMID 10780993.
^ Dawson LA, Nguyen HQ, Li P (November 2001). "The 5-HT(6) receptor antagonist SB-271046 selectively enhances excitatory neurotransmission in the rat frontal cortex and hippocampus". Neuropsychopharmacology 25 (5): 662–8. doi:10.1016/S0893-133X(01)00265-2. PMID 11682249.
^ King MV, Sleight AJ, Woolley ML, Topham IA, Marsden CA, Fone KC (August 2004). "5-HT6 receptor antagonists reverse delay-dependent deficits in novel object discrimination by enhancing consolidation--an effect sensitive to NMDA receptor antagonism". Neuropharmacology 47 (2): 195–204. doi:10.1016/j.neuropharm.2004.03.012. PMID 15223298.
^ ^a ^b ^c Upton N, Chuang TT, Hunter AJ, Virley DJ (July 2008). "5-HT6 receptor antagonists as novel cognitive enhancing agents for Alzheimer's disease". Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics 5 (3): 458–69. doi:10.1016/j.nurt.2008.05.008. PMID 18625457.
^ ^a ^b ^c ^d ^e ^f Schechter LE, Lin Q, Smith DL, et al. (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.
^ Lacroix LP, Dawson LA, Hagan JJ, Heidbreder CA (February 2004). "5-HT6 receptor antagonist SB-271046 enhances extracellular levels of monoamines in the rat medial prefrontal cortex". Synapse 51 (2): 158–64. doi:10.1002/syn.10288. PMID 14618683.
^ King MV, Marsden CA, Fone KC (September 2008). "A role for the 5-HT(1A), 5-HT4 and 5-HT6 receptors in learning and memory". Trends in Pharmacological Sciences 29 (9): 482–92. doi:10.1016/j.tips.2008.07.001. PMID 19086256.
^ Geldenhuys WJ, Van der Schyf CJ (2008). "Serotonin 5-HT6 receptor antagonists for the treatment of Alzheimer's disease". Current Topics in Medicinal Chemistry 8 (12): 1035–48. doi:10.2174/156802608785161420. PMID 18691131.
^ Geldenhuys WJ, Van der Schyf CJ (July 2009). "The serotonin 5-HT6 receptor: a viable drug target for treating cognitive deficits in Alzheimer's disease". Expert Review of Neurotherapeutics 9 (7): 1073–85. doi:10.1586/ern.09.51. PMID 19589055.
^ ^a ^b 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". Pharmacology & Therapeutics 117 (2): 207–31. doi:10.1016/j.pharmthera.2007.08.006. PMID 18068807.
^ Frassetto A, Zhang J, Lao JZ, et al. (October 2008). "Reduced sensitivity to diet-induced obesity in mice carrying a mutant 5-HT6 receptor". Brain Research 1236: 140–4. doi:10.1016/j.brainres.2008.08.012. PMID 18755168.
^ Carr GV, Schechter LE, Lucki I (March 2010). "Antidepressant and anxiolytic effects of selective 5-HT(6) receptor agonists in rats". Psychopharmacology 213 (2-3): 499–507. doi:10.1007/s00213-010-1798-7. PMC 2910165. PMID 20217056.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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. PMC 1752021. PMID 16865095.
^ 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. PMC 1751931. PMID 16783408.
^ 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.
^ Wu, J; Li, Q; Bezprozvanny, I (2008). "Evaluation of Dimebon in cellular model of Huntington's disease.". Molecular neurodegeneration 3: 15. doi:10.1186/1750-1326-3-15. PMC 2577671. PMID 18939977.
^ 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.
^ Liu KG, Robichaud AJ, Bernotas RC, et al. (November 2010). "5-Piperazinyl-3-sulfonylindazoles as potent and selective 5-hydroxytryptamine-6 antagonists". J. Med. Chem. 53 (21): 7639–46. doi:10.1021/jm1007825. PMID 20932009.
^ 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.
^ 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. doi:10.1212/wnl.58.5.828. PMID 11889255.

External links

"5-HT₆". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
serotonin 6 receptor at the US National Library of Medicine Medical Subject Headings (MeSH)

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

English Journal

Olanzapine for the prevention and treatment of chronic nausea and chemotherapy-induced nausea and vomiting.

Navari RM.Author information Indiana University School of Medicine South Bend, Harper Cancer Research Institute, 1234 Notre Dame Avenue, South Bend, IN 46617, USA. Electronic address: navari.1@nd.edu.AbstractOlanzapine is an atypical antipsychotic agent of the thiobenzodiazepine class. It blocks multiple neurotransmitter receptors including dopaminergic at D1, D2, D3, D4 brain receptors, serotonergic at 5-HT2a, 5-HT2c, 5-HT3, 5-HT6 receptors, catecholamines at alpha1 adrenergic receptors, acetylcholine at muscarinic receptors, and histamine at H1 receptors. Olanzapine has five times the affinity for 5-HT2 receptors than D2 receptors and has been used to treat schizophrenia and delirium. Olanzapine's activity at multiple receptors, particularly at the D2, 5-HT2c, and 5-HT3 receptors which appear to be involved in nausea and emesis, has prompted its use in the treatment of nausea and vomiting refractory to standard antiemetics. Case reports and formal clinical trials have demonstrated its efficacy in the treatment of chronic nausea, the prevention of chemotherapy-induced nausea and emesis, and the treatment of breakthrough chemotherapy-induced nausea and emesis. Phase II and phase III clinical trials have demonstrated that there is a significant improvement in nausea when olanzapine is added to guideline directed prophylactic antiemetic agents 5-HT3 receptor antagonists and tachykinin NK1 receptor antagonists in patients receiving moderately or highly emetogenic chemotherapy Common side effects of olanzapine when used over a period of months include weight gain as well as an association with the onset of diabetes mellitus, but these effects have not been seen with short term use of daily doses of less than one week.
European journal of pharmacology.Eur J Pharmacol.2014 Jan 5;722:180-6. doi: 10.1016/j.ejphar.2013.08.048. Epub 2013 Oct 21.
Olanzapine is an atypical antipsychotic agent of the thiobenzodiazepine class. It blocks multiple neurotransmitter receptors including dopaminergic at D1, D2, D3, D4 brain receptors, serotonergic at 5-HT2a, 5-HT2c, 5-HT3, 5-HT6 receptors, catecholamines at alpha1 adrenergic receptors, acetylcholine
PMID 24157985

Co-administration of 5-HT6 receptor antagonists with clozapine, risperidone, and a 5-HT2A receptor antagonist: effects on prepulse inhibition in rats.

Fijał K, Popik P, Nikiforuk A.Author information Department of Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.AbstractRATIONALE: Some novel antipsychotics manifest antagonistic activity at serotonin-6 receptors; however, little is known about the role of 5-HT6 receptors in ameliorating sensory gating deficits.
Psychopharmacology.Psychopharmacology (Berl).2014 Jan;231(1):269-81. doi: 10.1007/s00213-013-3234-2. Epub 2013 Aug 18.
RATIONALE: Some novel antipsychotics manifest antagonistic activity at serotonin-6 receptors; however, little is known about the role of 5-HT6 receptors in ameliorating sensory gating deficits.OBJECTIVE: We evaluated the effects of the combined administration of the 5-HT6 receptor antagonist SB 2710
PMID 23954911

The synthesis and comparative receptor binding affinities of novel, isomeric pyridoindolobenzazepine scaffolds.

Rajagopalan R1, Bandyopadhyaya A1, Rajagopalan DR1, Rajagopalan P2.Author information 1Daya Drug Discoveries, Inc., University of Missouri, St. Louis, One University Blvd., St. Louis, MO 63303, USA.2Daya Drug Discoveries, Inc., University of Missouri, St. Louis, One University Blvd., St. Louis, MO 63303, USA. Electronic address: ramajayam30@yahoo.com.AbstractCompounds 7, 8, and 9, derived from the novel scaffolds 3, 5, and 6, were synthesized and evaluated in vitro. The b,c→c,d shift of the E-phenyl ring resulted in a large decrease (ca. 20- to 1000-fold) in binding to the 5-HT2A, 5-HT2C and H2, receptors, and a modest decrease (ca. 10- to 20-fold) in binding to the 5-HT5A, D2, D5, and α1D, receptors. The b,c→d,e shift resulted in a large decrease in binding to the 5-HT1D, 5-HT2C, 5-HT6, and H1 receptors, a modest decrease in binding to 5-HT1A, 5-HT5A and D2, D5, α2B, and H2 receptors, and a large increase in affinity to the 5-HT3, 5-HT6, and σ1 receptors.
Bioorganic & medicinal chemistry letters.Bioorg Med Chem Lett.2013 Dec 11. pii: S0960-894X(13)01396-6. doi: 10.1016/j.bmcl.2013.12.024. [Epub ahead of print]
Compounds 7, 8, and 9, derived from the novel scaffolds 3, 5, and 6, were synthesized and evaluated in vitro. The b,c→c,d shift of the E-phenyl ring resulted in a large decrease (ca. 20- to 1000-fold) in binding to the 5-HT2A, 5-HT2C and H2, receptors, and a modest decrease (ca. 10- to 20-fold) in
PMID 24365159

Japanese Journal

Pathophysiological Roles of Serotonergic System in Regulating Extrapyramidal Motor Functions

Ohno Yukihiro,Shimizu Saki,Tokudome Kentaro
Biological and Pharmaceutical Bulletin 36(9), 1396-1400, 2013
… It is now known that multiple serotonin (5-hydroxytryptamine; … 5-HT) receptors regulate extrapyramidal motor functions, which are implicated in pathogenesis and/or treatment of various neurological disorders (e.g., Parkinson's disease and drug-induced extrapyramidal motor deficits). …
NAID 130003361521

セロトニン受容体拮抗薬 (特集アルツハイマー病治療薬の現状と期待される治療薬)

武田雅俊
老年精神医学雑誌 21(12), 1361-1367, 2010-12
NAID 40017427219

Stilbene Derivatives as Human 5-HT6 Receptor Antagonists from the Root of Caragana sinica

Kim Dong Hyuk,Kim Soon-Hee,Kim Hyoung Ja [他],Jin Changbae,Chung Kwang Chul,Rhim Hyewhon
Biological and Pharmaceutical Bulletin 33(12), 2024-2028, 2010
… The 5-HT6 receptor (5-HT6R) is a member of the class of recently discovered 5-hydroxytryptamine (5-HT) receptors. … Due to the lack of selective 5-HT6R ligands, the cellular signaling mechanisms of the 5-HT6R are poorly understood. …
NAID 130000402338

Related Pictures

★リンクテーブル★

「HT」

5-hydroxytryptamine (serotonin) receptor 6, G protein-coupled
Identifiers
Symbols	HTR6 ; 5-HT6; 5-HT6R
External IDs	OMIM: 601109 MGI: 1196627 HomoloGene: 673 IUPHAR: 5-HT6 ChEMBL: 3371 GeneCards: HTR6 Gene
Gene ontology
Molecular function	• histamine receptor activity; • serotonin receptor activity; • protein binding;
Cellular component	• plasma membrane; • integral to plasma membrane; • dendrite;
Biological process	• G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; • synaptic transmission; • brain development; • learning; • negative regulation of glutamate secretion; • negative regulation of gamma-aminobutyric acid secretion; • positive regulation of gamma-aminobutyric acid secretion; • negative regulation of acetylcholine secretion; • positive regulation of cAMP metabolic process; • response to estradiol stimulus; • positive regulation of dopamine secretion; • response to drug; • regulation of hormone secretion; • long-term synaptic potentiation;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;

　　[★]

「H」

　　[★]

[pmid8522988-1] 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. PMID 8522988.

[entrez-2] "Entrez Gene: HTR6 5-hydroxytryptamine (serotonin) receptor 6".

[pmid14965245-3] Woolley ML, Marsden CA, Fone KC (February 2004). "5-ht6 receptors". Current Drug Targets. CNS and Neurological Disorders 3 (1): 59–79. doi:10.2174/1568007043482561. PMID 14965245.

[pmid8389146-4] Ruat M, Traiffort E, Arrang JM, et al. (May 1993). "A novel rat serotonin (5-HT6) receptor: molecular cloning, localization and stimulation of cAMP accumulation". Biochemical and Biophysical Research Communications 193 (1): 268–76. doi:10.1006/bbrc.1993.1619. PMID 8389146.

[pmid9037500-5] Gérard C, Martres MP, Lefèvre K, et al. (January 1997). "Immuno-localization of serotonin 5-HT6 receptor-like material in the rat central nervous system". Brain Research 746 (1-2): 207–19. doi:10.1016/S0006-8993(96)01224-3. PMID 9037500.

[pmid10432491-6] Hamon M, Doucet E, Lefèvre K, et al. (August 1999). "Antibodies and antisense oligonucleotide for probing the distribution and putative functions of central 5-HT6 receptors". Neuropsychopharmacology 21 (2 Suppl): 68S–76S. doi:10.1016/S0893-133X(99)00044-5. PMID 10432491.

[pmid10780993-7] Dawson LA, Nguyen HQ, Li P (May 2000). "In vivo effects of the 5-HT(6) antagonist SB-271046 on striatal and frontal cortex extracellular concentrations of noradrenaline, dopamine, 5-HT, glutamate and aspartate". British Journal of Pharmacology 130 (1): 23–6. doi:10.1038/sj.bjp.0703288. PMC 1572041. PMID 10780993.

[pmid11682249-8] Dawson LA, Nguyen HQ, Li P (November 2001). "The 5-HT(6) receptor antagonist SB-271046 selectively enhances excitatory neurotransmission in the rat frontal cortex and hippocampus". Neuropsychopharmacology 25 (5): 662–8. doi:10.1016/S0893-133X(01)00265-2. PMID 11682249.

[pmid15223298-9] King MV, Sleight AJ, Woolley ML, Topham IA, Marsden CA, Fone KC (August 2004). "5-HT6 receptor antagonists reverse delay-dependent deficits in novel object discrimination by enhancing consolidation--an effect sensitive to NMDA receptor antagonism". Neuropharmacology 47 (2): 195–204. doi:10.1016/j.neuropharm.2004.03.012. PMID 15223298.

[pmid18625457-10] Upton N, Chuang TT, Hunter AJ, Virley DJ (July 2008). "5-HT6 receptor antagonists as novel cognitive enhancing agents for Alzheimer's disease". Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics 5 (3): 458–69. doi:10.1016/j.nurt.2008.05.008. PMID 18625457.

[pmid17625499-11] ^ ^a ^b ^c ^d ^e ^f Schechter LE, Lin Q, Smith DL, et al. (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.

[pmid14618683-12] Lacroix LP, Dawson LA, Hagan JJ, Heidbreder CA (February 2004). "5-HT6 receptor antagonist SB-271046 enhances extracellular levels of monoamines in the rat medial prefrontal cortex". Synapse 51 (2): 158–64. doi:10.1002/syn.10288. PMID 14618683.

[pmid19086256-13] King MV, Marsden CA, Fone KC (September 2008). "A role for the 5-HT(1A), 5-HT4 and 5-HT6 receptors in learning and memory". Trends in Pharmacological Sciences 29 (9): 482–92. doi:10.1016/j.tips.2008.07.001. PMID 19086256.

[pmid18691131-14] Geldenhuys WJ, Van der Schyf CJ (2008). "Serotonin 5-HT6 receptor antagonists for the treatment of Alzheimer's disease". Current Topics in Medicinal Chemistry 8 (12): 1035–48. doi:10.2174/156802608785161420. PMID 18691131.

[pmid19589055-15] Geldenhuys WJ, Van der Schyf CJ (July 2009). "The serotonin 5-HT6 receptor: a viable drug target for treating cognitive deficits in Alzheimer's disease". Expert Review of Neurotherapeutics 9 (7): 1073–85. doi:10.1586/ern.09.51. PMID 19589055.

[pmid18068807-16] 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". Pharmacology & Therapeutics 117 (2): 207–31. doi:10.1016/j.pharmthera.2007.08.006. PMID 18068807.

[pmid18755168-17] Frassetto A, Zhang J, Lao JZ, et al. (October 2008). "Reduced sensitivity to diet-induced obesity in mice carrying a mutant 5-HT6 receptor". Brain Research 1236: 140–4. doi:10.1016/j.brainres.2008.08.012. PMID 18755168.

[pmid20217056-18] Carr GV, Schechter LE, Lucki I (March 2010). "Antidepressant and anxiolytic effects of selective 5-HT(6) receptor agonists in rats". Psychopharmacology 213 (2-3): 499–507. doi:10.1007/s00213-010-1798-7. PMC 2910165. PMID 20217056.

[pmid18793848-19] 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.

[pmid19152787-20] 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.

[pmid15745826-21] 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.

[pmid16913710-22] 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.

[pmid15713394-23] 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.

[pmid16143522-24] 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.

[pmid18843410-25] 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.

[pmid16055331-26] 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.

[pmid10715164-27] 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.

[pmid17948978-28] 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.

[pmid19159187-29] 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.

[pmid16865095-30] 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. PMC 1752021. PMID 16865095.

[pmid16783408-31] 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. PMC 1751931. PMID 16783408.

[pmid16537199-32] 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.

[33] Wu, J; Li, Q; Bezprozvanny, I (2008). "Evaluation of Dimebon in cellular model of Huntington's disease.". Molecular neurodegeneration 3: 15. doi:10.1186/1750-1326-3-15. PMC 2577671. PMID 18939977.

[pmid19443217-34] 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.

[35] Liu KG, Robichaud AJ, Bernotas RC, et al. (November 2010). "5-Piperazinyl-3-sulfonylindazoles as potent and selective 5-hydroxytryptamine-6 antagonists". J. Med. Chem. 53 (21): 7639–46. doi:10.1021/jm1007825. PMID 20932009.

[pmid15531082-36] 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.

[pmid11889255-37] 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. doi:10.1212/wnl.58.5.828. PMID 11889255.

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5-HT6