5-HT2C receptor

{{short description|Serotonin receptor protein distributed mainly in the choroid plexus}} {{DISPLAYTITLE:5-HT_2C receptor}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox_gene}}

The '''5-HT_2C receptor''' is a subtype of the 5-HT2 receptor that binds the endogenous neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). Like all 5-HT2 receptors, it is a G protein-coupled receptor (GPCR) that is coupled to G_q/G₁₁ and mediates excitatory neurotransmission. ''HTR2C'' denotes the human gene encoding for the receptor,<ref name="entrez">{{cite web | title = Entrez Gene: HTR2C 5-hydroxytryptamine (serotonin) receptor 2C | url = https://www.ncbi.nlm.nih.gov/gene/3358?ordinalpos=2&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum }}</ref><ref name="Stam_1994">{{cite journal | vauthors = Stam NJ, Vanderheyden P, van Alebeek C, Klomp J, de Boer T, van Delft AM, Olijve W | title = Genomic organisation and functional expression of the gene encoding the human serotonin 5-HT2C receptor | journal = European Journal of Pharmacology | volume = 269 | issue = 3 | pages = 339–348 | date = November 1994 | pmid = 7895773 | doi = 10.1016/0922-4106(94)90042-6 }}</ref> that in humans is located on the X chromosome. As males have one copy of the gene and females have one of the two copies of the gene repressed, polymorphisms at this receptor can affect the two sexes to differing extent.

== Structure == At the cell surface the receptor exists as a homodimer.<ref name="HerrickDavis_2012">{{cite journal | vauthors = Herrick-Davis K, Grinde E, Lindsley T, Cowan A, Mazurkiewicz JE | title = Oligomer size of the serotonin 5-hydroxytryptamine 2C (5-HT2C) receptor revealed by fluorescence correlation spectroscopy with photon counting histogram analysis: evidence for homodimers without monomers or tetramers | journal = The Journal of Biological Chemistry | volume = 287 | issue = 28 | pages = 23604–23614 | date = July 2012 | pmid = 22593582 | pmc = 3390635 | doi = 10.1074/jbc.M112.350249 | doi-access = free }}</ref> The crystal structure has been known since 2018.<ref name="Peng_2018">{{cite journal | vauthors = Peng Y, McCorvy JD, Harpsøe K, Lansu K, Yuan S, Popov P, Qu L, Pu M, Che T, Nikolajsen LF, Huang XP, Wu Y, Shen L, Bjørn-Yoshimoto WE, Ding K, Wacker D, Han GW, Cheng J, Katritch V, Jensen AA, Hanson MA, Zhao S, Gloriam DE, Roth BL, Stevens RC, Liu ZJ | title = 5-HT_2C Receptor Structures Reveal the Structural Basis of GPCR Polypharmacology | journal = Cell | volume = 172 | issue = 4 | pages = 719–730.e14 | date = February 2018 | pmid = 29398112 | pmc = 6309861 | doi = 10.1016/j.cell.2018.01.001 }}</ref>

== Distribution == 5-HT_2C receptors are located mainly in the choroid plexus,<ref>{{cite journal | vauthors = Abramowski D, Rigo M, Duc D, Hoyer D, Staufenbiel M | title = Localization of the 5-hydroxytryptamine2C receptor protein in human and rat brain using specific antisera | journal = Neuropharmacology | volume = 34 | issue = 12 | pages = 1635–1645 | date = December 1995 | pmid = 8788961 | doi = 10.1016/0028-3908(95)00138-7 | s2cid = 45542707 }}</ref> and in rats is also found in many other brain regions in high concentrations, including parts of the hippocampus, anterior olfactory nucleus, substantia nigra, several brainstem nuclei, amygdala, subthalamic nucleus and lateral habenula. 5-HT_2C receptors are also found on epithelial cells lining the ventricles.<ref>{{cite journal | vauthors = Hoffman BJ, Mezey E | title = Distribution of serotonin 5-HT1C receptor mRNA in adult rat brain | journal = FEBS Letters | volume = 247 | issue = 2 | pages = 453–462 | date = April 1989 | pmid = 2714444 | doi = 10.1016/0014-5793(89)81390-0 | s2cid = 23825490 | doi-access = free | bibcode = 1989FEBSL.247..453H }}</ref>

== Function ==

The 5-HT_2C receptor is one of the many binding sites for serotonin. Activation of this receptor by serotonin inhibits dopamine and norepinephrine release in certain areas of the brain.<ref name="Alex_2005">{{cite journal | vauthors = Alex KD, Yavanian GJ, McFarlane HG, Pluto CP, Pehek EA | title = Modulation of dopamine release by striatal 5-HT2C receptors | journal = Synapse | volume = 55 | issue = 4 | pages = 242–251 | date = March 2005 | pmid = 15668911 | doi = 10.1002/syn.20109 | s2cid = 11405860 }}</ref>

5-HT_2C receptors are claimed to significantly regulate mood, anxiety, feeding, and reproductive behavior.<ref name="Heisler_2007">{{cite journal | vauthors = Heisler LK, Zhou L, Bajwa P, Hsu J, Tecott LH | title = Serotonin 5-HT(2C) receptors regulate anxiety-like behavior | journal = Genes, Brain, and Behavior | volume = 6 | issue = 5 | pages = 491–496 | date = July 2007 | pmid = 17451451 | doi = 10.1111/j.1601-183X.2007.00316.x | doi-access = free }}</ref> 5-HT_2C receptors regulate dopamine release in the striatum, prefrontal cortex, nucleus accumbens, hippocampus, hypothalamus, and amygdala, among others.

Research indicates that some suicide victims have an abnormally high number of 5-HT_2C receptors in the prefrontal cortex.<ref name="Niswender_2001">{{cite journal | vauthors = Niswender CM, Herrick-Davis K, Dilley GE, Meltzer HY, Overholser JC, Stockmeier CA, Emeson RB, Sanders-Bush E | title = RNA editing of the human serotonin 5-HT2C receptor. alterations in suicide and implications for serotonergic pharmacotherapy | journal = Neuropsychopharmacology | volume = 24 | issue = 5 | pages = 478–491 | date = May 2001 | pmid = 11282248 | doi = 10.1016/S0893-133X(00)00223-2 | doi-access = free }}</ref> Agomelatine, which is a 5-HT_2C and 5-HT_2B antagonist as well as a MT₁ and MT₂ agonist, is an effective antidepressant.<ref name="Guaiana_2013">{{cite journal | vauthors = Guaiana G, Gupta S, Chiodo D, Davies SJ, Haederle K, Koesters M | title = Agomelatine versus other antidepressive agents for major depression | journal = The Cochrane Database of Systematic Reviews | volume = 2013 | issue = 12 | date = December 2013 | pmid = 24343836 | pmc = 11289707 | doi = 10.1002/14651858.CD008851.pub2 | article-number = CD008851 }}</ref><ref name="Cipriani_2018">{{cite journal | vauthors = Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, Leucht S, Ruhe HG, Turner EH, Higgins JP, Egger M, Takeshima N, Hayasaka Y, Imai H, Shinohara K, Tajika A, Ioannidis JP, Geddes JR | title = Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis | journal = Lancet | volume = 391 | issue = 10128 | pages = 1357–1366 | date = April 2018 | pmid = 29477251 | pmc = 5889788 | doi = 10.1016/S0140-6736(17)32802-7 }}</ref> It has been found to act, through its 5-HT2C receptor antagonism, as a norepinephrine-dopamine disinhibitor because antagonism of 5-HT_2C results in an increase of dopamine and norepinephrine activity in the frontal cortex.<ref name="Stahl_2009">{{cite book | vauthors = Stahl SM, Muntner N | veditors = Felker A | chapter = Alpha 2 Antagonists as Serotonin and Norepinephrine Disinhibitors (SNDIs) and Serotonin Antagonist/Reuptake Inhibitors (SARIs). | title = Stahl's Illustrated Antidepressants. | pages = 83–96 | date = 2009 | publisher = Cambridge University Press }}</ref>

Conversely, many atypical antipsychotic and antidepressants act as 5-HT2C receptor antagonists, like Loxapine, an antipsychotic structurally related to Clozapine and its metabolite Amoxapine, which is an antidepressant in its own right, act as 5-HT2C receptor antagonist.<ref name="Roth_1994">{{cite journal | vauthors = Roth BL, Craigo SC, Choudhary MS, Uluer A, Monsma FJ, Shen Y, Meltzer HY, Sibley DR | title = Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 268 | issue = 3 | pages = 1403–1410 | date = March 1994 | pmid = 7908055 }}</ref> Fluoxetine acts as a direct 5-HT_2C antagonist in addition to inhibiting serotonin reuptake, however, the clinical significance of this action is variable.<ref name="Ni_1997">{{cite journal | vauthors = Ni YG, Miledi R | title = Blockage of 5HT2C serotonin receptors by fluoxetine (Prozac) | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 5 | pages = 2036–2040 | date = March 1997 | pmid = 9050900 | pmc = 20038 | doi = 10.1073/pnas.94.5.2036 | doi-access = free | bibcode = 1997PNAS...94.2036N }}</ref> Several tetracyclic antidepressants, including mirtazapine and Mianserin,<ref name="Stahl_2009" /> as well as certain Tricyclic antidepressant such as Amitriptyline and Clomipramine<ref name="Sanchez_1999">{{cite journal | vauthors = Sánchez C, Hyttel J | title = Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding | journal = Cellular and Molecular Neurobiology | volume = 19 | issue = 4 | pages = 467–489 | date = August 1999 | pmid = 10379421 | pmc = 11545528 | doi = 10.1023/a:1006986824213 }}</ref> are potent 5-HT_2C antagonists; this action may contribute to their efficacy.<ref name="PDSP">{{cite web | vauthors = Roth BL, Driscol J | title = PDSP K_i Database | author1-link = Bryan Roth | url = https://pdsp.unc.edu/databases/kidb.php | access-date = 14 August 2017 | work = Psychoactive Drug Screening Program (PDSP) | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health }}</ref><ref name="Anttila_2001">{{cite journal | vauthors = Anttila SA, Leinonen EV | title = A review of the pharmacological and clinical profile of mirtazapine | journal = CNS Drug Reviews | volume = 7 | issue = 3 | pages = 249–264 | year = 2001 | pmid = 11607047 | pmc = 6494141 | doi = 10.1111/j.1527-3458.2001.tb00198.x }}</ref><ref name="Frazer_1997">{{cite journal | vauthors = Frazer A | title = Pharmacology of antidepressants | journal = Journal of Clinical Psychopharmacology | volume = 17 | issue = Suppl 1 | pages = 2S–18S | date = April 1997 | pmid = 9090573 | doi = 10.1097/00004714-199704001-00002 }}</ref><ref name="Stahl_2009" /> An overactivity of 5-HT_2C receptors may contribute to depressive and anxiety symptoms in a certain population of patients. Activation of 5-HT_2C by serotonin is responsible for many of the negative side effects of SSRI and SNRI medications, such as sertraline, paroxetine, venlafaxine, and others. Some of the initial anxiety caused by SSRIs is due to excessive signalling at 5-HT_2C receptors. 5-HT_2C receptors exhibit constitutive activity ''in vivo'', and may retain the ability to influence neurotransmission in the absence of ligand occupancy. Thus, 5-HT_2C receptors do not require binding by a ligand (serotonin) in order to exhibit influence on neurotransmission. Inverse agonists may be required to fully extinguish 5-HT_2C constitutive activity, and may prove useful in the treatment of 5-HT_2C-mediated conditions in the absence of typical serotonin activity.<ref name="Berg_2005">{{cite journal | vauthors = Berg KA, Harvey JA, Spampinato U, Clarke WP | title = Physiological relevance of constitutive activity of 5-HT2A and 5-HT2C receptors | journal = Trends in Pharmacological Sciences | volume = 26 | issue = 12 | pages = 625–630 | date = December 2005 | pmid = 16269190 | doi = 10.1016/j.tips.2005.10.008 }}</ref> In addition to the evidence for a role of 5-HT_2C receptor stimulation in depressive symptoms there also is evidence that activation of 5-HT_2C receptors may have beneficial effects upon certain aspects of depression, one group of researchers found that direct stimulation of 5-HT_2C receptors with a 5-HT_2C agonist reduced cognitive deficits in mice with a TPH2 loss-of-function mutation.<ref name="DelGuidice_2014">{{cite journal | vauthors = Del'Guidice T, Lemay F, Lemasson M, Levasseur-Moreau J, Manta S, Etievant A, Escoffier G, Doré FY, Roman FS, Beaulieu JM | title = Stimulation of 5-HT2C receptors improves cognitive deficits induced by human tryptophan hydroxylase 2 loss of function mutation | journal = Neuropsychopharmacology | volume = 39 | issue = 5 | pages = 1125–1134 | date = April 2014 | pmid = 24196946 | pmc = 3957106 | doi = 10.1038/npp.2013.313 }}</ref>

5-HT_2C receptors mediate the release and increase of extracellular dopamine in response to many drugs,<ref name="Esposito_2006">{{cite journal | vauthors = Esposito E | title = Serotonin-dopamine interaction as a focus of novel antidepressant drugs | journal = Current Drug Targets | volume = 7 | issue = 2 | pages = 177–185 | date = February 2006 | pmid = 16475959 | doi = 10.2174/138945006775515455 }}</ref><ref name="Bubar_2006">{{cite journal | vauthors = Bubar MJ, Cunningham KA | title = Serotonin 5-HT2A and 5-HT2C receptors as potential targets for modulation of psychostimulant use and dependence | journal = Current Topics in Medicinal Chemistry | volume = 6 | issue = 18 | pages = 1971–1985 | year = 2006 | pmid = 17017968 | doi = 10.2174/156802606778522131 }}</ref> including caffeine, nicotine, amphetamine, morphine, cocaine, and others. 5-HT_2C antagonism increases dopamine release in response to reinforcing drugs, and many dopaminergic stimuli. Feeding, social interaction, and sexual activity all release dopamine subject to inhibition of 5-HT_2C. Increased 5-HT_2C expression reduces dopamine release in both the presence and absence of stimuli.

Conditions that increase cytokine levels in the human body may have potential to raise 5-HT_2C gene expression in the brain. This could possibly comprise a link between viral infections and associated depression. Cytokine therapy has been shown to increase 5-HT_2C gene expression, resulting in increased activity of 5-HT_2C receptors in the brain {{Citation needed|date=August 2015}}.

== Endocrinology == Serotonin is involved in basal and stress-induced regulation of hypothalamus and pituitary gland hormones such as prolactin, adrenocorticotropic hormone (ACTH), vasopressin and oxytocin, mainly via actions of receptor subtypes 5-HT_2A and 5-HT_2C.<ref name="Jrgensen_2007">{{cite journal | vauthors = Jørgensen HS | title = Studies on the neuroendocrine role of serotonin | journal = Danish Medical Bulletin | volume = 54 | issue = 4 | pages = 266–288 | date = November 2007 | pmid = 18208678 }}</ref> Therefore, the 5-HT_2C receptor is a significant modulator of the hypothalamic–pituitary–adrenal axis (HPA axis).<ref name="Heisler_2007a">{{cite journal | vauthors = Heisler LK, Pronchuk N, Nonogaki K, Zhou L, Raber J, Tung L, Yeo GS, O'Rahilly S, Colmers WF, Elmquist JK, Tecott LH | title = Serotonin activates the hypothalamic-pituitary-adrenal axis via serotonin 2C receptor stimulation | journal = The Journal of Neuroscience | volume = 27 | issue = 26 | pages = 6956–6964 | date = June 2007 | pmid = 17596444 | pmc = 6672238 | doi = 10.1523/JNEUROSCI.2584-06.2007 | doi-access = free }}</ref> The HPA axis is the main controller of acute sympathetic stress responses related to fight-or-flight response. Prolonged activation and disturbances of the HPA axis contribute to depressive and anxiety symptoms seen in many psychopathological conditions.

Stimulation of 5-HT_2C receptors leads to increase of corticotropin releasing hormone (CRH) and vasopressin mRNA in the paraventricular nucleus and proopiomelanocortin in the anterior pituitary lobe. In rats, restraint stress (which can produce depressive symptoms if being chronic) induces secretion of prolactin, ACTH, vasopressin and oxytocin which is partially mediated via 5-HT_2C receptor. Responses during such conditions as dehydration or haemorrhage causes the release of oxytocin via serotonergic response that is partly mediated by 5-HT_2C. In addition, peripheral release of vasopressin involves serotonergic response which is partially mediated via 5-HT_2C.

Expression of the 5-HT_2C receptor in the CNS is modulated by female sex hormones estradiol and progesterone. Combination of the hormones decrease the receptor concentration in the ventral hippocampus in rats and could thus affect mood.<ref name="Birzniece_2002">{{cite journal | vauthors = Birzniece V, Johansson IM, Wang MD, Bäckström T, Olsson T | title = Ovarian hormone effects on 5-hydroxytryptamine(2A) and 5-hydroxytryptamine(2C) receptor mRNA expression in the ventral hippocampus and frontal cortex of female rats | journal = Neuroscience Letters | volume = 319 | issue = 3 | pages = 157–161 | date = February 2002 | pmid = 11834317 | doi = 10.1016/S0304-3940(01)02570-8 | s2cid = 6902168 }}</ref>

== Genetics ==

Many human polymorphisms have been identified influencing the expression of 5-HT_2C. Significant correlations are suggested, specifically in relation to psychiatric disorders such as depression, OCD, and anxiety-related conditions. Polymorphisms also correlate with susceptibility to a number of conditions including substance use disorders and obesity. There are indications that the alternative splicing of the 5-HT_2C receptor is regulated by a snoRNA called SNORD115, the deletion of which is associated with Prader–Willi syndrome.<ref name="Kishore_2006">{{cite journal | vauthors = Kishore S, Stamm S | title = The snoRNA HBII-52 regulates alternative splicing of the serotonin receptor 2C | journal = Science | volume = 311 | issue = 5758 | pages = 230–232 | date = January 2006 | pmid = 16357227 | doi = 10.1126/science.1118265 | s2cid = 44527461 | doi-access = free | bibcode = 2006Sci...311..230K }}</ref><ref name="Sahoo_2008">{{cite journal | vauthors = Sahoo T, del Gaudio D, German JR, Shinawi M, Peters SU, Person RE, Garnica A, Cheung SW, Beaudet AL | title = Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA cluster | journal = Nature Genetics | volume = 40 | issue = 6 | pages = 719–721 | date = June 2008 | pmid = 18500341 | pmc = 2705197 | doi = 10.1038/ng.158 }}</ref> As the human gene is located in the X chromosome, males have only one copy of the gene whereas women have two, meaning that mutations in the gene affect the phenotype of men even when the allele would be recessive in nature. As women have two copies of the gene, but only one allele is expressed in each cell, they are a mosaic for polymorphisms, meaning that one genetic variant may be prevalent in one tissue and another variant will be prevalent in a different tissue (as with all other x-linked genetic variations).

==Ligands== ===Agonists=== {{Main|5-HT2C receptor agonist}}

{{div col|colwidth=15em}} * A-372,159 * AL-38022A * Aporphines and noraporphines (e.g., MQ02-439, nornuciferine, asimilobine, 11-chloroasimilobine, 11-methoxyasimilobine, (''S'')-glaucine)<ref name="QinZhangWang2025">{{cite journal | vauthors = Qin W, Zhang B, Wang Q, Jiang G, Cui J, Chen F, Wang L, Chen J, Tian S, Zhen XC, Shui W, Ye N | title = Discovery of New N-H Aporphine Derivatives As Brain-Penetrant Gq-Biased 5-HT2C Receptor Agonists and Dual 5-HT2C/5-HT2A Receptor Agonists | journal = J Med Chem | volume = 68 | issue = 21 | pages = 23300–23323 | date = November 2025 | pmid = 41108743 | doi = 10.1021/acs.jmedchem.5c02115 | url = }}</ref><ref name="MaoZhangLi2020">{{cite journal | vauthors = Mao Q, Zhang B, Li W, Tian S, Shui W, Ye N | title = Identification of Novel 1-O-Substituted Aporphine Analogues as Potent 5-HT2C Receptor Agonists | journal = ACS Chem Neurosci | volume = 11 | issue = 4 | pages = 549–559 | date = February 2020 | pmid = 31968160 | doi = 10.1021/acschemneuro.9b00563 | url = }}</ref><ref name="HengCheeThy2019">{{cite journal | vauthors = Heng HL, Chee CF, Thy CK, Tee JT, Chin SP, Herr DR, Buckle MJ, Paterson IC, Doughty SW, Abd Rahman N, Chung LY | title = In vitro functional evaluation of isolaureline, dicentrine and glaucine enantiomers at 5-HT2 and α1 receptors | journal = Chem Biol Drug Des | volume = 93 | issue = 2 | pages = 132–138 | date = February 2019 | pmid = 30216681 | doi = 10.1111/cbdd.13390 | url = }}</ref> * ATHX-105 * Bexicaserin * BMB-101 * BMB-105 * BMB-201 * Centhaquine<ref name="Adhikari_2025">{{cite journal | vauthors = Adhikari AS, Yadav A, Pandit S, Kumar S, Pandey VK, Maurya AK, Umrao D, Chand D, Maity D, Gayen JR, Srivastava KR, Yadav PN, Majumdar N | title = Synthesis and Evaluation of Novel Aza-Aromatics as Dual 5-HT2A and 5-HT2C Receptor Agonists | journal = ACS Medicinal Chemistry Letters | date = 26 November 2025 | doi = 10.1021/acsmedchemlett.5c00505 | issn = 1948-5875 | url = https://pubs.acs.org/doi/10.1021/acsmedchemlett.5c00505 | access-date = 29 November 2025 | url-access = subscription }}</ref> * CP-132,484 * CP-809,101 * CPD-1<ref name="Rodriguez_2017">{{cite journal | vauthors = Rodriguez MM, Overshiner C, Leander JD, Li X, Morrow D, Conway RG, Nelson DL, Briner K, Witkin JM | title = Behavioral Effects of a Novel Benzofuranyl-Piperazine Serotonin-2C Receptor Agonist Suggest a Potential Therapeutic Application in the Treatment of Obsessive-Compulsive Disorder | journal = Frontiers in Psychiatry | volume = 8 | pages = 89 | year = 2017 | pmid = 28588509 | pmc = 5438973 | doi = 10.3389/fpsyt.2017.00089 | doi-access = free }}</ref> * DLX-2270 * Fenfluramine * KB-128 * Lisuride * Lorcaserin * LY03020 * Mesulergine * MK-212 * Naphthylisopropylamine * Norfenfluramine * NU-1223 * ORG-12962 * ORG-37684 * Oxaflozane * PF-04479745<ref name="Storer_2014">{{cite journal | vauthors = Storer RI, Brennan PE, Brown AD, Bungay PJ, Conlon KM, Corbett MS, DePianta RP, Fish PV, Heifetz A, Ho DK, Jessiman AS, McMurray G, de Oliveira CA, Roberts LR, Root JA, Shanmugasundaram V, Shapiro MJ, Skerten M, Westbrook D, Wheeler S, Whitlock GA, Wright J | title = Multiparameter optimization in CNS drug discovery: design of pyrimido[4,5-d]azepines as potent 5-hydroxytryptamine 2C (5-HT₂C) receptor agonists with exquisite functional selectivity over 5-HT₂A and 5-HT₂B receptors | journal = Journal of Medicinal Chemistry | volume = 57 | issue = 12 | pages = 5258–5269 | date = June 2014 | pmid = 24878222 | doi = 10.1021/jm5003292 }}</ref> * PNU-22394 * PNU-181731 * PRX-00933 * Psychedelics ** Lysergamides (e.g., LSD) ** Phenethylamines (e.g., mescaline, 2C-B, DOI, DOM, MDA, 25I-NBOMe) ** Phenylpiperazines (e.g., mCPP, TFMPP) ** Tryptamines (e.g., DMT, psilocin, psilocybin, 5-MeO-DMT, bufotenin, CPI-CG-8) * Ro60-0175 * Vabicaserin * VR-1065 * WAY-629 * WAY-161,503 * WAY-163,909 * WAY-261240 * YM-348 {{div col end}}

===Antagonists=== {{div col|colwidth=15em}} * Agomelatine * CEPC<ref>{{cite journal | vauthors = McCorvy JD, Harland AA, Maglathlin R, Nichols DE | title = A 5-HT(2C) receptor antagonist potentiates a low dose amphetamine-induced conditioned place preference | journal = Neuroscience Letters | volume = 505 | issue = 1 | pages = 10–13 | date = November 2011 | pmid = 21827831 | pmc = 3213641 | doi = 10.1016/j.neulet.2011.07.036 }}</ref> * Clozapine * Cyclobenzaprine * Eltoprazine * Etoperidone * Flibanserin<ref>{{cite journal | vauthors = Stahl SM, Sommer B, Allers KA | title = Multifunctional pharmacology of flibanserin: possible mechanism of therapeutic action in hypoactive sexual desire disorder | journal = The Journal of Sexual Medicine | volume = 8 | issue = 1 | pages = 15–27 | date = January 2011 | pmid = 20840530 | doi = 10.1111/j.1743-6109.2010.02032.x }}</ref> * Fluoxetine * FR260010 * Methysergide * Mianserin * Mirtazapine * Nefazodone * Norfluoxetine * O-Desmethyltramadol * Olanzapine * Promethazine * Puerarin * RS-102,221 * SB-200,646 * SB-221,284 * SB-228,357 * SB-242,084 * SDZ SER-082 * Tedatioxetine * Tramadol * Trazodone {{div col end}}

====Peripherally selective antagonists==== * BW-501C67 * Sarpogrelate * Xylamidine

===Inverse agonists=== {{div col|colwidth=15em}} * Antidepressants {{Citation needed |date=March 2017}} ** Tricyclics (Amitriptyline and Nortriptyline most notably)<ref>Roth BL, Driscol J. "PDSP K_i Database". ''Psychoactive Drug Screening Program (PDSP)''. University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.</ref> ** Tetracyclics (Mirtazapine, Mianserin, Amoxapine, etc.) * Antihistamines (Cyproheptadine, Hydroxyzine, Latrepirdine, etc.) * Antipsychotics ** Typicals (Chlorpromazine, Fluphenazine, Loxapine, Thioridazine, etc.) ** Atypicals (Clozapine, Olanzapine, Risperidone, Ziprasidone, etc.) * Cinanserin * Deramciclane * Ketanserin * LY-53,857 * Metergoline * Methiothepin * Pizotifen * Ritanserin * S-32212<ref name="Dekeyne_2012">{{cite journal | vauthors = Dekeyne A, Brocco M, Loiseau F, Gobert A, Rivet JM, Di Cara B, Cremers TI, Flik G, Fone KC, Watson DJ, Papp M, Sharp T, Serres F, Cespuglio R, Olivier B, Chan JS, Lavielle G, Millan MJ | title = S32212, a novel serotonin type 2C receptor inverse agonist/α2-adrenoceptor antagonist and potential antidepressant: II. A behavioral, neurochemical, and electrophysiological characterization | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 340 | issue = 3 | pages = 765–780 | date = March 2012 | pmid = 22178753 | doi = 10.1124/jpet.111.187534 | s2cid = 11363664 }}</ref> * SB-206,553 * SB-228,357 * SB-242,084 * SB-243,213 * SB-247853 * Tenilapine <ref>Haut FL, Habiger C, Speck K, Wurst K, Mayer P, Korber JN, Müller T, Magauer T. Synthetic Entry to Polyfunctionalized Molecules through the [3+2]-Cycloaddition of Thiocarbonyl Ylides. ''J Am Chem Soc''. 2019 Aug 28;141(34):13352-13357. {{doi|10.1021/jacs.9b07729}} {{pmid|31408334}}</ref> {{div col end}}

===Positive allosteric modulators=== Exogenous PAMs of the serotonin 5-HT_2C receptor include:<ref name="De_Deurwaerdere_2020">{{cite journal | vauthors = De Deurwaerdère P, Chagraoui A, Cunningham KA | title = Editorial: Contemporary Perspective on 5-HT_2C Receptor Function and Its Pharmacological Targeting | journal = Frontiers in Pharmacology | volume = 11 | date = 2020 | pmid = 33324228 | pmc = 7724505 | doi = 10.3389/fphar.2020.606414 | doi-access = free | article-number = 606414 }}</ref>

* CYD-1-79<ref name="Wild_2019">{{cite journal | vauthors = Wild CT, Miszkiel JM, Wold EA, Soto CA, Ding C, Hartley RM, White MA, Anastasio NC, Cunningham KA, Zhou J | title = Design, Synthesis, and Characterization of 4-Undecylpiperidine-2-carboxamides as Positive Allosteric Modulators of the Serotonin (5-HT) 5-HT_2C Receptor | journal = Journal of Medicinal Chemistry | volume = 62 | issue = 1 | pages = 288–305 | date = January 2019 | pmid = 29620897 | pmc = 6533912 | doi = 10.1021/acs.jmedchem.8b00401 }}</ref> * CTW-0415<ref name="Wold_2020">{{cite journal | vauthors = Wold EA, Garcia EJ, Wild CT, Miszkiel JM, Soto CA, Chen J, Pazdrak K, Fox RG, Anastasio NC, Cunningham KA, Zhou J | title = Discovery of 4-Phenylpiperidine-2-Carboxamide Analogues as Serotonin 5-HT_2C Receptor-Positive Allosteric Modulators with Enhanced Drug-like Properties | journal = Journal of Medicinal Chemistry | volume = 63 | issue = 14 | pages = 7529–7544 | date = July 2020 | pmid = 32567857 | pmc = 8434884 | doi = 10.1021/acs.jmedchem.9b01953 }}</ref> * VA012<ref>{{cite journal | vauthors = García-Cárceles J, Decara JM, Vázquez-Villa H, Rodríguez R, Codesido E, Cruces J, Brea J, Loza MI, Alén F, Botta J, McCormick PJ, Ballesteros JA, Benhamú B, Rodríguez de Fonseca F, López-Rodríguez ML | title = A Positive Allosteric Modulator of the Serotonin 5-HT_2C Receptor for Obesity | journal = Journal of Medicinal Chemistry | volume = 60 | issue = 23 | pages = 9575–9584 | date = December 2017 | pmid = 29116785 | doi = 10.1021/acs.jmedchem.7b00994 }}</ref>

== Interactions ==

The 5-HT_2C receptor has been shown to interact with MPDZ.<ref name="Becamel_2001">{{cite journal | vauthors = Becamel C, Figge A, Poliak S, Dumuis A, Peles E, Bockaert J, Lubbert H, Ullmer C | title = Interaction of serotonin 5-hydroxytryptamine type 2C receptors with PDZ10 of the multi-PDZ domain protein MUPP1 | journal = The Journal of Biological Chemistry | volume = 276 | issue = 16 | pages = 12974–12982 | date = April 2001 | pmid = 11150294 | doi = 10.1074/jbc.M008089200 | doi-access = free }}</ref><ref name="Ullmer_1998">{{cite journal | vauthors = Ullmer C, Schmuck K, Figge A, L��bbert H | title = Cloning and characterization of MUPP1, a novel PDZ domain protein | journal = FEBS Letters | volume = 424 | issue = 1–2 | pages = 63–68 | date = March 1998 | pmid = 9537516 | doi = 10.1016/S0014-5793(98)00141-0 | doi-access = free | bibcode = 1998FEBSL.424...63U }}</ref>

== RNA editing ==

5HT2CR pre-mRNA can be the subject of RNA editing.<ref name="Burns_1997">{{cite journal | vauthors = Burns CM, Chu H, Rueter SM, Hutchinson LK, Canton H, Sanders-Bush E, Emeson RB | title = Regulation of serotonin-2C receptor G-protein coupling by RNA editing | journal = Nature | volume = 387 | issue = 6630 | pages = 303–308 | date = May 1997 | pmid = 9153397 | doi = 10.1038/387303a0 | s2cid = 4247011 | bibcode = 1997Natur.387..303B }}</ref> It is the only serotonin receptor as well as the only member of the large family of 7 transmembrane receptors (7TMRs) known to be edited. Different levels of editing result in a variety of effects on receptor function.

=== Type ===

The type of RNA editing that occurs in the pre-mRNA of the 5HT2CR is Adenosine to Inosine (A to I) editing.

A to I RNA editing is catalyzed by a family of adenosine deaminases acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre-mRNAs and deaminate them to inosine. Inosines are recognised as guanosine by the cells translational machinery. There are three members of the ADAR family ADARs 1–3 with ADAR1 and ADAR2 being the only enzymatically active members. ADAR3 is thought to have a regulatory role in the brain. ADAR1 and ADAR2 are widely expressed in tissues while ADAR3 is restricted to the brain. The double stranded regions of RNA are formed by base-pairing between residues in the close to region of the editing site with residues usually in a neighboring intron but can be an exonic sequence. The region that base pairs with the editing region is known as an Editing Complementary Sequence (ECS).

ADARs bind interact directly with the dsRNA substrate via their double stranded RNA binding domains. If an editing site occurs within a coding sequence, it can result in a codon change. This can lead to translation of a protein isoform due to a change in its primary protein structure. Therefore, editing can also alter protein function. A to I editing occurs in a non coding RNA sequences such as introns, untranslated regions (UTRs), LINEs, SINEs ( especially Alu repeats) The function of A to I editing in these regions is thought to involve creation of splice sites and retention of RNAs in the nucleus amongst others.

=== Location ===

Editing occurs in 5 different closely located sites within exon 5, which corresponds to the second intracellular loop of the final protein. The sites are known as A, B, C′ (previously called E), C and D, and are predicted to occur within amino acid positions 156, 158 and 160. Several codon changes can occur due to A-to-I editing at these sites. Thirty-two different mRNA variants can occur leading to 24 different protein isoforms.

#An Isoleucine to Valine (I/V) at amino acid position 157,161. #An Isoleucine to a Methionine(I/M) at amino acid position 157 #An Aspartate to a Serine (N/S)at 159 #An Aspartate to Asparagine(N/D) at 159 #An Asparagine to a Glycine(N/G) at 159.

These codon changes which can occur due to A to I editing at these sites can lead to a maximum of 32 different mRNA variants leading to 24 different protein isoforms. The number of protein isoforms is less than 32 since some amino acids are encoded by more than one codon.<ref name="Fitzgerald_1999">{{cite journal | vauthors = Fitzgerald LW, Iyer G, Conklin DS, Krause CM, Marshall A, Patterson JP, Tran DP, Jonak GJ, Hartig PR | title = Messenger RNA editing of the human serotonin 5-HT2C receptor | journal = Neuropsychopharmacology | volume = 21 | issue = 2 Suppl | pages = 82S–90S | date = August 1999 | pmid = 10432493 | doi = 10.1016/S0893-133X(99)00004-4 | doi-access = free }}</ref> Another editing site, site F has also been located in the exon complementary sequence (ECS) of intron 5.<ref name="Flomen_2004">{{cite journal | vauthors = Flomen R, Knight J, Sham P, Kerwin R, Makoff A | title = Evidence that RNA editing modulates splice site selection in the 5-HT2C receptor gene | journal = Nucleic Acids Research | volume = 32 | issue = 7 | pages = 2113–2122 | year = 2004 | pmid = 15087490 | pmc = 407821 | doi = 10.1093/nar/gkh536 }}</ref> The ECS required for formation of double stranded RNA structure is found within intron 5.<ref name="Burns_1997" />

=== Conservation ===

RNA editing of this receptor occurs at 4 locations in the rat.<ref name="Burns_1997" /> Editing also occurs in the mouse.<ref name="Hackler_2006">{{cite journal | vauthors = Hackler EA, Airey DC, Shannon CC, Sodhi MS, Sanders-Bush E | title = 5-HT(2C) receptor RNA editing in the amygdala of C57BL/6J, DBA/2J, and BALB/cJ mice | journal = Neuroscience Research | volume = 55 | issue = 1 | pages = 96–104 | date = May 2006 | pmid = 16580757 | doi = 10.1016/j.neures.2006.02.005 | s2cid = 3799598 }}</ref> The initial demonstration of RNA editing in rat.<ref name="Burns_1997" /> The predominant isoform in rat brain is VNV which differs from the most common type found in humans.<ref name="Burns_1997" /><ref name="Niswender_1999">{{cite journal | vauthors = Niswender CM, Copeland SC, Herrick-Davis K, Emeson RB, Sanders-Bush E | title = RNA editing of the human serotonin 5-hydroxytryptamine 2C receptor silences constitutive activity | journal = The Journal of Biological Chemistry | volume = 274 | issue = 14 | pages = 9472–9478 | date = April 1999 | pmid = 10092629 | doi = 10.1074/jbc.274.14.9472 | doi-access = free }}</ref> The editing complementary sequence is known to be conserved across Mammalia.

=== Regulation ===

The 5-HT_2c receptor is the only serotonin receptor edited despite its close sequence similarities to other family members.<ref name="Niswender_1999" /> 5HT2CR is different due to possessing an imperfect inverted repeat at the end of exon 5 and the beginning of intron 5 allowing formation of an RNA duplex producing the dsRNA required by ADARs for editing. Disruption of this inverted repeat was demonstrated to cease all editing.<ref name="Burns_1997" /> The different 5HT2CR mRNA isoforms are expressed differently throughout the brain, yet not all of the 24 have been detected perhaps due to tissue specific expression or low frequency editing of a particular type. Those isoforms that are not expressed at all or at a very low frequency are linked by being edited only at site C' and/or site B but not at site A. Some examples of differences in frequency of editing and site edited in different parts of the human brain of 5HT2CR include low frequency of editing in cerebellum and nearly all editing is at site D while in the hippocampus editing frequency is higher with site A being the main editing site. Site C' is only found edited in the thalamus. The most common isoform in human brain is the VSV isoform.<ref name="Fitzgerald_1999" /><ref name="Niswender_1999" /><ref name="Wang_2000">{{cite journal | vauthors = Wang Q, O'Brien PJ, Chen CX, Cho DS, Murray JM, Nishikura K | title = Altered G protein-coupling functions of RNA editing isoform and splicing variant serotonin2C receptors | journal = Journal of Neurochemistry | volume = 74 | issue = 3 | pages = 1290–1300 | date = March 2000 | pmid = 10693963 | doi = 10.1046/j.1471-4159.2000.741290.x | doi-access = free }}</ref>

Mice knock out and other studies have been used to determine which ADAR enzyme are involved in editing. Editing at A and B sites has been demonstrated to be due to ADAR1 editing.<ref name="Yang_2004">{{cite journal | vauthors = Yang W, Wang Q, Kanes SJ, Murray JM, Nishikura K | title = Altered RNA editing of serotonin 5-HT2C receptor induced by interferon: implications for depression associated with cytokine therapy | journal = Brain Research. Molecular Brain Research | volume = 124 | issue = 1 | pages = 70–78 | date = April 2004 | pmid = 15093687 | doi = 10.1016/j.molbrainres.2004.02.010 }}</ref><ref name="Sukma_2005">{{cite journal | vauthors = Sukma M, Tohda M, Watanabe H, Matsumoto K | title = The mRNA expression differences of RNA editing enzymes in differentiated and undifferentiated NG108-15 cells | journal = Journal of Pharmacological Sciences | volume = 98 | issue = 4 | pages = 467–470 | date = August 2005 | pmid = 16082172 | doi = 10.1254/jphs.SC0050074 | doi-access = free }}</ref><ref name="Tohda_2004">{{cite journal | vauthors = Tohda M, Sukma M, Watanabe H | title = RNA editing and short variant of serotonin 2C receptor mRNA in neuronally differentiated NG108-15 cells | journal = Journal of Pharmacological Sciences | volume = 96 | issue = 2 | pages = 164–169 | date = October 2004 | pmid = 15492466 | doi = 10.1254/jphs.FP0040227 | doi-access = free }}</ref> Also since ADAR1 expression is increased in response to the presence of interferon α, it was also observed that editing at A and B sites was also increased because of this.<ref name="Yang_2004" /> C' and D sites require ADAR2 and editing is decreased by the presence of ADAR1 with editing of C' site only observed in ADAR1 double knock out mice.<ref name="Hartner_2004">{{cite journal | vauthors = Hartner JC, Schmittwolf C, Kispert A, Müller AM, Higuchi M, Seeburg PH | title = Liver disintegration in the mouse embryo caused by deficiency in the RNA-editing enzyme ADAR1 | journal = The Journal of Biological Chemistry | volume = 279 | issue = 6 | pages = 4894–4902 | date = February 2004 | pmid = 14615479 | doi = 10.1074/jbc.M311347200 | doi-access = free }}</ref> The C site has been shown to be mainly edited by ADAR2 but in presence of upregulated expression of ADAR1, there was an increase in editing of this site and the enzymes presence can also result in limited editing in ADAR 2 knock out mice.<ref name="Yang_2004" /><ref name="Hartner_2004" /> This demonstrates that there must be some form interaction between the two A to I editing enzymes. Also such interactions and tissue specific expression of ADARs interaction may explain the variety in editing patterns in different regions of the brain.

====Consequences====

Second, the editing pattern controls the amount of the 5-HT2CR mRNA that leads to the expression of full-length protein through the modulation of alternative splice site selection 76,77. Among three alternative splice donor sites (GU1 to GU3; Fig. 4C), GU2 is the only site that forms the mature mRNA to produce the functional, full-length 5-HT2CR protein. Unedited pre-mRNAs tend to be spliced at the GU1 site, resulting in the truncated, non-functional protein if translated 76,77. However, most pre-mRNAs edited at more than one position are spliced at GU2 77. Thus, when editing is inefficient, increased splicing at GU1 may act as a control mechanism to decrease biosynthesis of the 5-HT2CR-INI and thereby limit serotonin response. Third, RNA editing controls the ultimate physiological output of constitutively active receptors by affecting the cell surface expression of the 5-HT2CR. The 5-HT2CR-VGV, which displays the lowest level of constitutive activity, is fully expressed at the cell surface under basal conditions and is rapidly internalized in the presence of agonist 78; additionally, in vitro, LSD shows negligible activity with this isoform.<ref>{{cite journal | vauthors = Backstrom JR, Chang MS, Chu H, Niswender CM, Sanders-Bush E | title = Agonist-directed signaling of serotonin 5-HT2C receptors: differences between serotonin and lysergic acid diethylamide (LSD) | journal = Neuropsychopharmacology | volume = 21 | issue = 2 Suppl | pages = 77S–81S | date = August 1999 | pmid = 10432492 | doi = 10.1016/S0893-133X(99)00005-6 | s2cid = 25007217 | doi-access = free }}</ref> In contrast, the 5-HT2CR-INI is constitutively internalized and accumulates in endosomes 78.

'''Structure'''

As mentioned editing results in several codon changes. The editing sites are found in the second intracellular domain of the protein which is also the receptors G protein coupling domain. Therefore, editing of these sites can affect the affinity of the receptor for G protein binding.<ref name="Burns_1997" />

'''Function'''

Editing results in reduced affinity for specific G proteins which in turn affects internal signalling via second messengers (Phospholipase C signalling system). The fully edited isoform, VGV, considerably reduces 5-HT potency, G-protein coupling and agonist binding, compared to the unedited protein isoform, INI. 72–76. Most evidence for the effect of editing on function comes from downstream measurements of receptor activity, radio ligand binding and functional studies. Inhibitory effects are linked to the extent of editing. Those isoforms with a higher level of editing require higher levels of serotonin to activate the phospholipase c pathway. Unedited INI form has a greater tendency to isomerise to an active form which can more easily interact with G proteins. This indicates that RNA editing here may be a mechanism for regulating neuronal excitability by stabilising receptor signalling.<ref name="Burns_1997" /><ref name="Niswender_1999" />

Editing is also thought to function in cell surface expression of the receptor subtype. The fully edited VGV, which has the lowest level of constitutive activity, is fully expressed at the cell surface while the non-edited INI is internalised and accumulates in endosome.<ref name="Marion_2004">{{cite journal | vauthors = Marion S, Weiner DM, Caron MG | title = RNA editing induces variation in desensitization and trafficking of 5-hydroxytryptamine 2c receptor isoforms | journal = The Journal of Biological Chemistry | volume = 279 | issue = 4 | pages = 2945–2954 | date = January 2004 | pmid = 14602721 | doi = 10.1074/jbc.M308742200 | doi-access = free }}</ref>

Editing is also thought to influence splicing. Three different spliced isoforms of the receptor exist. Editing regulates the amount of 5HT2CR mRNA which leads to translation of the full length protein selection of alternative splice sites. t76,77. These splice sites are termed Gu1, Gu2, GU3. Only GU2 site splicing results in translation of the full length receptor while editing at GU1 is known to result in translation of a truncated protein. This is thought to be a regulatory mechanism to decrease the amount of unedited isoform INI to limit serotonin response when editing is inefficient. Most of the pre-mRNAs which are edited are spliced at the GU2 site.<ref name="Flomen_2004" /><ref name="Wang_2000" />

'''Dysregulation'''

Serotonin family of receptors are often linked to pathology of several human mental conditions such as Schizophrenia, anxiety, Bipolar disorder and major depression.<ref name="Baxter_1995">{{cite journal | vauthors = Baxter G, Kennett G, Blaney F, Blackburn T | title = 5-HT2 receptor subtypes: a family re-united? | journal = Trends in Pharmacological Sciences | volume = 16 | issue = 3 | pages = 105–110 | date = March 1995 | pmid = 7792930 | doi = 10.1016/S0165-6147(00)88991-9 }}</ref> There have been several experimental investigations into the effects of alternative editing patterns of the 5HT2CR and these conditions with a wide variability in results especially those relating to schizophrenia.<ref name="Iwamoto_2003">{{cite journal | vauthors = Iwamoto K, Kato T | title = RNA editing of serotonin 2C receptor in human postmortem brains of major mental disorders | journal = Neuroscience Letters | volume = 346 | issue = 3 | pages = 169–172 | date = August 2003 | pmid = 12853111 | doi = 10.1016/S0304-3940(03)00608-6 | s2cid = 24977282 }}</ref> Some studies have noted that there is an increase in RNA editing at site A in depressed suicide victims.<ref name="Niswender_2001" /><ref name="Iwamoto_2003" /> E site editing was observed to be increased in individuals with major depression.<ref name="Gurevich_2002">{{cite journal | vauthors = Gurevich I, Tamir H, Arango V, Dwork AJ, Mann JJ, Schmauss C | title = Altered editing of serotonin 2C receptor pre-mRNA in the prefrontal cortex of depressed suicide victims | journal = Neuron | volume = 34 | issue = 3 | pages = 349–356 | date = April 2002 | pmid = 11988167 | doi = 10.1016/S0896-6273(02)00660-8 | doi-access = free }}</ref> In rat models this increase is also observed and can be reversed with fluoxetine with some suggestion that E site editing maybe linked to major depression.<ref name="Iwamoto_2005">{{cite journal | vauthors = Iwamoto K, Nakatani N, Bundo M, Yoshikawa T, Kato T | title = Altered RNA editing of serotonin 2C receptor in a rat model of depression | journal = Neuroscience Research | volume = 53 | issue = 1 | pages = 69–76 | date = September 2005 | pmid = 16005997 | doi = 10.1016/j.neures.2005.06.001 | s2cid = 25363004 }}</ref><ref name="Gurevich_2002a">{{cite journal | vauthors = Gurevich I, Englander MT, Adlersberg M, Siegal NB, Schmauss C | title = Modulation of serotonin 2C receptor editing by sustained changes in serotonergic neurotransmission | journal = The Journal of Neuroscience | volume = 22 | issue = 24 | pages = 10529–10532 | date = December 2002 | pmid = 12486144 | pmc = 6758441 | doi = 10.1523/JNEUROSCI.22-24-10529.2002 | doi-access = free }}</ref>

== See also == * 5-HT receptor * 5-HT₂ receptor * Anxiety/Aggression-Driven Depression * Norepinephrine-dopamine disinhibitor

== References == {{Reflist|33em}}

==External links== * {{UCSC gene info|HTR2C}} * {{PDBe-KB2|P28335|5-hydroxytryptamine receptor 2C}}

== Further reading == {{Refbegin|33em}} * {{cite journal | vauthors = Niswender CM, Sanders-Bush E, Emeson RB | title = Identification and characterization of RNA editing events within the 5-HT2C receptor | journal = Annals of the New York Academy of Sciences | volume = 861 | issue = 1 | pages = 38–48 | date = December 1998 | pmid = 9928237 | doi = 10.1111/j.1749-6632.1998.tb10171.x | s2cid = 25127011 | bibcode = 1998NYASA.861...38N }} * {{cite journal | vauthors = Hoyer D, Hannon JP, Martin GR | title = Molecular, pharmacological and functional diversity of 5-HT receptors | journal = Pharmacology, Biochemistry, and Behavior | volume = 71 | issue = 4 | pages = 533–554 | date = April 2002 | pmid = 11888546 | doi = 10.1016/S0091-3057(01)00746-8 | s2cid = 25543069 }} * {{cite journal | vauthors = Raymond JR, Mukhin YV, Gelasco A, Turner J, Collinsworth G, Gettys TW, Grewal JS, Garnovskaya MN | title = Multiplicity of mechanisms of serotonin receptor signal transduction | journal = Pharmacology & Therapeutics | volume = 92 | issue = 2–3 | pages = 179–212 | year = 2002 | pmid = 11916537 | doi = 10.1016/S0163-7258(01)00169-3 }} * {{cite journal | vauthors = Van Oekelen D, Luyten WH, Leysen JE | title = 5-HT2A and 5-HT2C receptors and their atypical regulation properties | journal = Life Sciences | volume = 72 | issue = 22 | pages = 2429–2449 | date = April 2003 | pmid = 12650852 | doi = 10.1016/S0024-3205(03)00141-3 }} * {{cite journal | vauthors = Reynolds GP, Templeman LA, Zhang ZJ | title = The role of 5-HT2C receptor polymorphisms in the pharmacogenetics of antipsychotic drug treatment | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 29 | issue = 6 | pages = 1021–1028 | date = July 2005 | pmid = 15953671 | doi = 10.1016/j.pnpbp.2005.03.019 | s2cid = 30964513 }} * {{cite journal | vauthors = Millan MJ | title = Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies | journal = Therapie | volume = 60 | issue = 5 | pages = 441–460 | year = 2006 | pmid = 16433010 | doi = 10.2515/therapie:2005065 }} * {{cite journal | vauthors = Milatovich A, Hsieh CL, Bonaminio G, Tecott L, Julius D, Francke U | title = Serotonin receptor 1c gene assigned to X chromosome in human (band q24) and mouse (bands D-F4) | journal = Human Molecular Genetics | volume = 1 | issue = 9 | pages = 681–684 | date = December 1992 | pmid = 1302605 | doi = 10.1093/hmg/1.9.681 }} * {{cite journal | vauthors = Saltzman AG, Morse B, Whitman MM, Ivanshchenko Y, Jaye M, Felder S | title = Cloning of the human serotonin 5-HT2 and 5-HT1C receptor subtypes | journal = Biochemical and Biophysical Research Communications | volume = 181 | issue = 3 | pages = 1469–1478 | date = December 1991 | pmid = 1722404 | doi = 10.1016/0006-291X(91)92105-S }} * {{cite journal | vauthors = Lappalainen J, Zhang L, Dean M, Oz M, Ozaki N, Yu DH, Virkkunen M, Weight F, Linnoila M, Goldman D | title = Identification, expression, and pharmacology of a Cys23-Ser23 substitution in the human 5-HT2c receptor gene (HTR2C) | journal = Genomics | volume = 27 | issue = 2 | pages = 274–279 | date = May 1995 | pmid = 7557992 | doi = 10.1006/geno.1995.1042 | url = https://zenodo.org/record/1229657 }} * {{cite journal | vauthors = Tecott LH, Sun LM, Akana SF, Strack AM, Lowenstein DH, Dallman MF, Julius D | title = Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors | journal = Nature | volume = 374 | issue = 6522 | pages = 542–546 | date = April 1995 | pmid = 7700379 | doi = 10.1038/374542a0 | s2cid = 4368727 | bibcode = 1995Natur.374..542T }} * {{cite journal | vauthors = Stam NJ, Vanderheyden P, van Alebeek C, Klomp J, de Boer T, van Delft AM, Olijve W | title = Genomic organisation and functional expression of the gene encoding the human serotonin 5-HT2C receptor | journal = European Journal of Pharmacology | volume = 269 | issue = 3 | pages = 339–348 | date = November 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pmid = 9241279 | doi = 10.1038/ng0897-387 | s2cid = 21333874 }} * {{cite journal | vauthors = Ullmer C, Schmuck K, Figge A, Lübbert H | title = Cloning and characterization of MUPP1, a novel PDZ domain protein | journal = FEBS Letters | volume = 424 | issue = 1–2 | pages = 63–68 | date = March 1998 | pmid = 9537516 | doi = 10.1016/S0014-5793(98)00141-0 | doi-access = free | bibcode = 1998FEBSL.424...63U }} * {{cite journal | vauthors = Samochowiec J, Smolka M, Winterer G, Rommelspacher H, Schmidt LG, Sander T | title = Association analysis between a Cys23Ser substitution polymorphism of the human 5-HT2c receptor gene and neuronal hyperexcitability | journal = American Journal of Medical Genetics | volume = 88 | issue = 2 | pages = 126–130 | date = April 1999 | pmid = 10206230 | doi = 10.1002/(SICI)1096-8628(19990416)88:2<126::AID-AJMG6>3.0.CO;2-M }} * {{cite journal | vauthors = Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, 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{{G protein-coupled receptors}} {{Cell signaling}} {{Serotonergics}} {{Obsessive–compulsive disorder}}

{{DEFAULTSORT:5-Ht2c Receptor}} Category:Serotonin receptors