5-HT2C receptor

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5-hydroxytryptamine (serotonin) receptor 2C
Identifiers
Symbols HTR2C ; 5-HT2C; HTR1C
External IDs Template:OMIM5 Template:MGI HomoloGene: 20242
RNA expression pattern
More reference expression data
Orthologs
Template:GNF Ortholog box
Species Human Mouse
Entrez n/a n/a
Ensembl n/a n/a
UniProt n/a n/a
RefSeq (mRNA) n/a n/a
RefSeq (protein) n/a n/a
Location (UCSC) n/a n/a
PubMed search n/a n/a

Overview

5-hydroxytryptamine (serotonin) receptor 2C, also known as HTR2C, is a 5-HT2 receptor, but also denotes the human gene encoding it.


Function

Ligands

Numerous (ex-)prescription, illicit and research drugs contain a 5-HT2C component in their binding profile, including fluoxetine, mianserin, clozapine, agomelatine, dextro-norfenfluramine, psilocin, DOI, α-methyl-serotonin, MK-212, m-CPP, FG-7142,[1] Ro60-0175,[2] mesulergine, metergoline, ritanserin, methiothepin, 5-methoxygramine, and many more.[3] Some compounds with a more pronounced selectivity for the 5-HT2C receptor subtype are listed below. Note, that in the following context the term "functional selectivity" does not refer to differentiation of transductional pathways.

Agonists

  • (5aR,9R)-2-[(cyclopropylmethoxy)methyl]-5,5a,6,7,8,9-hexahydro-9-methyl-pyrido[3′,2′:4,5]pyrrolo[1,2-a]pyrazine: potent, full agonist with an outstanding selectivity profile[6]
  • (R)-9-ethyl-1,3,4,10b-tetrahydro-7-trifluoromethylpyrazino[2,1-a]isoindol-6(2H)-one: agonist, >300-fold functional selectivity over 5-HT2B and >70-fold over 5-HT2A[7]
  • Lorcaserin: full agonist, fair selectivity profile[8][9][10]

Antagonists

  • FR260010: silent antagonist, high affinity, selective over 5-HT2A and many other receptors; orally active.[11]
  • RS-102221: silent antagonist, 100-fold selectivity compared to the 5-HT2A and -HT2B receptor subtypes[12]

Mixed response

A more extensive examination on signal transduction was carried out for

Receptor regulation

Agonists promote 5-HT2C receptor internalization leading to tachyphylaxis.[15]

See also

References

  1. ↑ Hackler EA, Turner GH, Gresch PJ, Sengupta S, Deutch AY, Avison MJ, Gore JC, Sanders-Bush E (2007). "5-Hydroxytryptamine2C receptor contribution to m-chlorophenylpiperazine and N-methyl-beta-carboline-3-carboxamide-induced anxiety-like behavior and limbic brain activation". J. Pharmacol. Exp. Ther. 320 (3): 1023–9. doi:10.1124/jpet.106.113357. PMID 17138863.
  2. ↑ Higgins GA, Ouagazzal AM, Grottick AJ (2001). "Influence of the 5-HT(2C) receptor antagonist SB242,084 on behaviour produced by the 5-HT2 agonist Ro60-0175 and the indirect 5-HT agonist dexfenfluramine". Br. J. Pharmacol. 133 (4): 459–66. doi:10.1038/sj.bjp.0704082. PMID 11399662.
  3. ↑ Lacivita E, Leopoldo M (2006). "Selective agents for serotonin 2C (5-HT2C) receptor". Curr Top Med Chem. 6 (18): 1927–70. doi:10.2174/156802606778522168. PMID 17017967.
  4. ↑ Kimura Y, Hatanaka K, Naitou Y, Maeno K, Shimada I, Koakutsu A, Wanibuchi F, Yamaguchi T (2004). "Pharmacological profile of YM348, a novel, potent and orally active 5-HT2C receptor agonist". Eur. J. Pharmacol. 483 (1): 37–43. doi:10.1016/j.ejphar.2003.10.004. PMID 14709324.
  5. ↑ Shimada I, Maeno K, Kazuta K, Kubota H, Kimizuka T, Kimura Y, Hatanaka K, Naitou Y, Wanibuchi F, Sakamoto S, Tsukamoto S (2008). "Synthesis and structure-activity relationships of a series of substituted 2-(1H-furo[2,3-g]indazol-1-yl)ethylamine derivatives as 5-HT2C receptor agonists". Bioorg. Med. Chem. 16 (4): 1966–82. doi:10.1016/j.bmc.2007.10.100. PMID 18035544.
  6. ↑ Richter HG, Adams DR, Benardeau A, Bickerdike MJ, Bentley JM, Blench TJ, Cliffe IA, Dourish C, Hebeisen P, Kennett GA, Knight AR, Malcolm CS, Mattei P, Misra A, Mizrahi J, Monck NJ, Plancher JM, Roever S, Roffey JR, Taylor S, Vickers SP (2006). "Synthesis and biological evaluation of novel hexahydro-pyrido[3',2':4,5]pyrrolo[1,2-a]pyrazines as potent and selective 5-HT2C receptor agonists". Bioorg. Med. Chem. Lett. 16 (5): 1207–11. doi:10.1016/j.bmcl.2005.11.083. PMID 16361098.
  7. ↑ Wacker DA, Varnes JG, Malmstrom SE, Cao X, Hung CP, Ung T, Wu G, Zhang G, Zuvich E, Thomas MA, Keim WJ, Cullen MJ, Rohrbach KW, Qu Q, Narayanan R, Rossi K, Janovitz E, Lehman-McKeeman L, Malley MF, Devenny J, Pelleymounter MA, Miller KJ, Robl JA (2007). "Discovery of (R)-9-ethyl-1,3,4,10b-tetrahydro-7-trifluoromethylpyrazino[2,1-a]isoindol- 6(2H)-one, a selective, orally active agonist of the 5-HT2C receptor". J. Med. Chem. 50 (6): 1365–79. doi:10.1021/jm0612968. PMID 17315987.
  8. ↑ Thomsen WJ, Grottick AJ, Menzaghi F, Reyes-Saldana H, Espitia S, Yuskin D, Whelan K, Martin M, Morgan M, Chen W, Al-Shama H, Smith B, Chalmers D, Behan D (2008). "Lorcaserin, A Novel Selective Human 5-HT2C Agonist: In Vitro and In Vivo Pharmacological Characterization". J. Pharmacol. Exp. Ther. doi:10.1124/jpet.107.133348. PMID 18252809.
  9. ↑ Smith BM, Smith JM, Tsai JH, Schultz JA, Gilson CA, Estrada SA, Chen RR, Park DM, Prieto EB, Gallardo CS, Sengupta D, Thomsen WJ, Saldana HR, Whelan KT, Menzaghi F, Webb RR, Beeley NR (2005). "Discovery and SAR of new benzazepines as potent and selective 5-HT2C receptor agonists for the treatment of obesity". Bioorg. Med. Chem. Lett. 15 (5): 1467–70. doi:10.1016/j.bmcl.2004.12.080. PMID 15713408.
  10. ↑ Lam DD, Przydzial MJ, Ridley SH, Yeo GS, Rochford JJ, O'Rahilly S, Heisler LK (2008). "Serotonin 5-HT2C Receptor Agonist Promotes Hypophagia via Downstream Activation of Melanocortin 4 Receptors". Endocrinology. 149 (3): 1323–8. doi:10.1210/en.2007-1321. PMID 18039773.
  11. ↑ Harada K, Aota M, Inoue T, Matsuda R, Mihara T, Yamaji T, Ishibashi K, Matsuoka N (2006). "Anxiolytic activity of a novel potent serotonin 5-HT2C receptor antagonist FR260010: a comparison with diazepam and buspirone". Eur. J. Pharmacol. 553 (1–3): 171–84. doi:10.1016/j.ejphar.2006.09.042. PMID 17074317.
  12. ↑ Bonhaus DW, Weinhardt KK, Taylor M, DeSouza A, McNeeley PM, Szczepanski K, Fontana DJ, Trinh J, Rocha CL, Dawson MW, Flippin LA, Eglen RM (1997). "RS-102221: a novel high affinity and selective, 5-HT2C receptor antagonist". Neuropharmacology. 36 (4–5): 621–9. doi:10.1016/S0028-3908(97)00049-X. PMID 9225287.
  13. ↑ Wood MD, Reavill C, Trail B, Wilson A, Stean T, Kennett GA, Lightowler S, Blackburn TP, Thomas D, Gager TL, Riley G, Holland V, Bromidge SM, Forbes IT, Middlemiss DN (2001). "SB-243213; a selective 5-HT2C receptor inverse agonist with improved anxiolytic profile: lack of tolerance and withdrawal anxiety". Neuropharmacology. 41 (2): 186–99. doi:10.1016/S0028-3908(01)00054-5. PMID 11489455.
  14. ↑ Berg KA, Navailles S, Sanchez TA, Silva YM, Wood MD, Spampinato U, Clarke WP (2006). "Differential effects of 5-methyl-1-{[2-[(2-methyl-3-pyridyl)oxyl]-5-pyridyl]carbamoyl}-6-trifluoromethylindone (SB 243213) on 5-hydroxytryptamine (2C) receptor-mediated responses". J. Pharmacol. Exp. Ther. 319 (1): 260–8. doi:10.1124/jpet.106.104448. PMID 16807362.
  15. ↑ Schlag BD, Lou Z, Fennell M, Dunlop J (2004). "Ligand dependency of 5-hydroxytryptamine 2C receptor internalization". J. Pharmacol. Exp. Ther. 310 (3): 865–70. doi:10.1124/jpet.104.067306. PMID 15113845.

Further reading

  • Niswender CM, Sanders-Bush E, Emeson RB (1999). "Identification and characterization of RNA editing events within the 5-HT2C receptor". Ann. N. Y. Acad. Sci. 861: 38–48. PMID 9928237.
  • Hoyer D, Hannon JP, Martin GR (2002). "Molecular, pharmacological and functional diversity of 5-HT receptors". Pharmacol. Biochem. Behav. 71 (4): 533–54. PMID 11888546.
  • Raymond JR, Mukhin YV, Gelasco A; et al. (2002). "Multiplicity of mechanisms of serotonin receptor signal transduction". Pharmacol. Ther. 92 (2–3): 179–212. PMID 11916537.
  • Van Oekelen D, Luyten WH, Leysen JE (2003). "5-HT2A and 5-HT2C receptors and their atypical regulation properties". Life Sci. 72 (22): 2429–49. PMID 12650852.
  • Reynolds GP, Templeman LA, Zhang ZJ (2005). "The role of 5-HT2C receptor polymorphisms in the pharmacogenetics of antipsychotic drug treatment". Prog. Neuropsychopharmacol. Biol. Psychiatry. 29 (6): 1021–8. doi:10.1016/j.pnpbp.2005.03.019. PMID 15953671.
  • Millan MJ (2006). "Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies". Therapie. 60 (5): 441–60. PMID 16433010.
  • Milatovich A, Hsieh CL, Bonaminio G; et al. (1993). "Serotonin receptor 1c gene assigned to X chromosome in human (band q24) and mouse (bands D-F4)". Hum. Mol. Genet. 1 (9): 681–4. PMID 1302605.
  • Saltzman AG, Morse B, Whitman MM; et al. (1992). "Cloning of the human serotonin 5-HT2 and 5-HT1C receptor subtypes". Biochem. Biophys. Res. Commun. 181 (3): 1469–78. PMID 1722404.
  • Lappalainen J, Zhang L, Dean M; et al. (1995). "Identification, expression, and pharmacology of a Cys23-Ser23 substitution in the human 5-HT2c receptor gene (HTR2C)". Genomics. 27 (2): 274–9. doi:10.1006/geno.1995.1042. PMID 7557992.
  • Tecott LH, Sun LM, Akana SF; et al. (1995). "Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors". Nature. 374 (6522): 542–6. doi:10.1038/374542a0. PMID 7700379.
  • Stam NJ, Vanderheyden P, van Alebeek C; et al. (1995). "Genomic organisation and functional expression of the gene encoding the human serotonin 5-HT2C receptor". Eur. J. Pharmacol. 269 (3): 339–48. PMID 7895773.
  • Xie E, Zhu L, Zhao L, Chang LS (1996). "The human serotonin 5-HT2C receptor: complete cDNA, genomic structure, and alternatively spliced variant". Genomics. 35 (3): 551–61. doi:10.1006/geno.1996.0397. PMID 8812491.
  • Burns CM, Chu H, Rueter SM; et al. (1997). "Regulation of serotonin-2C receptor G-protein coupling by RNA editing". Nature. 387 (6630): 303–8. doi:10.1038/387303a0. PMID 9153397.
  • Brennan TJ, Seeley WW, Kilgard M; et al. (1997). "Sound-induced seizures in serotonin 5-HT2c receptor mutant mice". Nat. Genet. 16 (4): 387–90. doi:10.1038/ng0897-387. PMID 9241279.
  • Ullmer C, Schmuck K, Figge A, Lübbert H (1998). "Cloning and characterization of MUPP1, a novel PDZ domain protein". FEBS Lett. 424 (1–2): 63–8. PMID 9537516.
  • Samochowiec J, Smolka M, Winterer G; et al. (1999). "Association analysis between a Cys23Ser substitution polymorphism of the human 5-HT2c receptor gene and neuronal hyperexcitability". Am. J. Med. Genet. 88 (2): 126–30. PMID 10206230.
  • Cargill M, Altshuler D, Ireland J; et al. (1999). "Characterization of single-nucleotide polymorphisms in coding regions of human genes". Nat. Genet. 22 (3): 231–8. doi:10.1038/10290. PMID 10391209.
  • Marshall SE, Bird TG, Hart K, Welsh KI (2000). "Unified approach to the analysis of genetic variation in serotonergic pathways". Am. J. Med. Genet. 88 (6): 621–7. PMID 10581480.
  • Backstrom JR, Price RD, Reasoner DT, Sanders-Bush E (2000). "Deletion of the serotonin 5-HT2C receptor PDZ recognition motif prevents receptor phosphorylation and delays resensitization of receptor responses". J. Biol. Chem. 275 (31): 23620–6. doi:10.1074/jbc.M000922200. PMID 10816555.

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

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