Nomenclature: 5-HT2C receptor

Family: 5-Hydroxytryptamine receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Contents

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 458 Xq24 HTR2C 5-hydroxytryptamine (serotonin) receptor 2C, G protein-coupled 68
Mouse 7 459 X D-F4 Htr2c 5-hydroxytryptamine (serotonin) receptor 2C 23,72
Rat 7 460 Xq34-q35.1 Htr2c 5-hydroxytryptamine (serotonin) receptor 2C, G protein-coupled 4
Previous and Unofficial Names
Names References
5-HT1C 53
HTR1C
5-HT2C
5-hydroxytryptamine (serotonin) receptor 2C
5-HTR2C
5HT-1C
5-HT-1C
5-HT1C
5-hydroxytryptamine receptor 1C
5-hydroxytryptamine receptor 2C
serotonin 1c receptor
serotonin receptor 2C
5-HT2C receptor
5-HT2cR
5HT1c
SR1
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligand(s)
5-HT
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]DOI Rn Full agonist 9.1 pKd 3
pKd 9.1 [3]
[125I]DOI Hs Full agonist 8.7 – 9.0 pKd 21
pKd 8.7 – 9.0 [21]
YM348 Hs Full agonist 9.0 pKi 36
pKi 9.0 [36]
ergotamine Hs Partial agonist 8.7 pKi 37
pKi 8.7 [37]
methysergide Rn Partial agonist 8.7 pKi 64
pKi 8.7 [64]
(+)-LSD Hs Full agonist 8.2 – 9.0 pKi 21,37
pKi 8.2 – 9.0 [21,37]
AL-37350A Hs Full agonist 8.5 pKi 42
pKi 8.5 [42]
LSD Hs Full agonist 8.2 – 8.6 pKi 19
pKi 8.2 – 8.6 [19]
methylergonovine Hs Full agonist 8.3 pKi 37
pKi 8.3 [37]
VER-3323 Hs Full agonist 8.2 pKi 37
pKi 8.2 [37]
lisuride Hs Partial agonist 7.9 – 8.3 pKi 19,21,46
pKi 7.9 – 8.3 [19,21,46]
org 37684 Hs Full agonist 8.1 pKi 37
pKi 8.1 [37]
(+)-DOI Hs Full agonist 8.1 pKi 37
pKi 8.1 [37]
(R)-DOI Hs Full agonist 7.4 – 8.7 pKi 21,37,42,49
pKi 8.4 [42]
pKi 7.4 – 8.7 [21,37,49]
Ro 60-0175 Hs Full agonist 7.7 – 8.2 pKi 36-37
pKi 7.7 – 8.2 [36-37]
DOI Hs Full agonist 7.2 – 8.6 pKi 19,49,65
pKi 7.2 – 8.6 [19,49,65]
ergotamine Rn Partial agonist 7.9 pKi 64
pKi 7.9 [64]
methylergonovine Rn Full agonist 7.9 pKi 64
pKi 7.9 [64]
DOB Hs Full agonist 6.8 – 8.9 pKi 19,37,49
pKi 6.8 – 8.9 [19,37,49]
lorcaserin Hs Full agonist 7.8 pKi 69
pKi 7.8 [69]
org 12962 Hs Full agonist 7.8 pKi 37
pKi 7.8 [37]
α-methyl-5-HT Hs Full agonist 6.9 – 8.6 pKi 21,37
pKi 6.9 – 8.6 [21,37]
5-HT Hs Full agonist 6.8 – 8.6 pKi 19,21,36-37,42
pKi 6.8 – 8.6 [19,21,36-37,42]
S 16924 Hs Full agonist 7.7 pKi 44
pKi 7.7 [44]
aripiprazole Hs Full agonist 7.6 pKi 39
pKi 7.6 [39]
m-CPP Hs Partial agonist 6.5 – 8.5 pKi 19,21,36-37,49,65
pKi 6.5 – 8.5 [19,21,36-37,49,65]
WAY-163909 Hs Full agonist 6.7 – 8.0 pKi 18
pKi 6.7 – 8.0 [18]
5-HT Rn Full agonist 6.7 – 7.9 pKi 31,64
pKi 6.7 – 7.9 [31,64]
5-MeOT Hs Full agonist 6.7 – 7.8 pKi 19
pKi 6.7 – 7.8 [19]
m-CPP Rn Partial agonist 7.2 pKi 64
pKi 7.2 [64]
TFMPP Hs Full agonist 6.5 – 7.8 pKi 19,37
pKi 6.5 – 7.8 [19,37]
GR-127935 Hs Partial agonist 7.0 pKi 58
pKi 7.0 [58]
BW723C86 Hs Full agonist 6.9 – 7.1 pKi 37,65
pKi 6.9 – 7.1 [37,65]
SB 216641 Hs Partial agonist 6.8 pKi 58
pKi 6.8 [58]
RU 24969 Hs Full agonist 6.8 pKi 37
pKi 6.8 [37]
quipazine Hs Full agonist 5.9 – 7.3 pKi 19,21,37
pKi 5.9 – 7.3 [19,21,37]
5-MeO-DMT Hs Full agonist 6.2 – 7.0 pKi 21
pKi 6.2 – 7.0 [21]
DOB Rn Full agonist 6.6 pKi 31
pKi 6.6 [31]
oxymetazoline Hs Full agonist 6.3 – 6.8 pKi 21
pKi 6.3 – 6.8 [21]
pergolide Hs Partial agonist 6.5 pKi 46
pKi 6.5 [46]
tryptamine Hs Full agonist 5.6 – 7.2 pKi 19,37
pKi 5.6 – 7.2 [19,37]
5-MeOT Rn Full agonist 6.3 pKi 31
pKi 6.3 [31]
MK-212 Hs Full agonist 5.6 – 7.0 pKi 19,37,65
pKi 5.6 – 7.0 [19,37,65]
cabergoline Hs Full agonist 6.2 pKi 46
pKi 6.2 [46]
BRL-15572 Hs Partial agonist 6.2 pKi 58
pKi 6.2 [58]
bromocriptine Hs Partial agonist 6.1 pKi 46
pKi 6.1 [46]
5-CT Hs Full agonist 5.2 – 6.7 pKi 19,37
pKi 5.2 – 6.7 [19,37]
CGS-12066 Hs Full agonist 5.6 pKi 37
pKi 5.6 [37]
8-OH-DPAT Hs Full agonist 5.6 pKi 37
pKi 5.6 [37]
LY344864 Hs Full agonist 5.5 pKi 54
pKi 5.5 [54]
SL65.0155 Hs Partial agonist 5.3 pKi 48
pKi 5.3 [48]
(-)-quinpirole Hs Full agonist 5.0 – 5.5 pKi 37,46
pKi 5.0 – 5.5 [37,46]
lorcaserin Hs Full agonist 8.1 pEC50 69
pEC50 8.1 [69]
[3H]LSD Hs Agonist - -
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]mesulergine Hs Inverse agonist 9.3 – 8.7 pKd 21,61
pKd 9.3 – 8.7 (Kd 5x10-10 – 2.2x10-9 M) [21,61]
methysergide Rn Antagonist 9.3 pKi 31
pKi 9.3 [31]
mesulergine Rn Inverse agonist 9.2 pKi 31
pKi 9.2 [31]
mianserin Rn Antagonist 8.8 – 9.4 pKi 31,60
pKi 8.8 – 9.4 [31,60]
sertindole Hs Inverse agonist 9.0 – 9.2 pKi 33,39
pKi 9.0 – 9.2 [33,39]
SB 228357 Hs Antagonist 9.0 – 9.1 pKi 7,63
pKi 9.0 – 9.1 [7,63]
FR260010 Hs Antagonist 9.0 pKi 30
pKi 9.0 (Ki 1.1x10-9 M) [30]
mesulergine Hs Inverse agonist 8.7 – 9.3 pKi 29,37-38
pKi 8.7 – 9.3 [29,37-38]
ritanserin Hs Antagonist 8.2 – 9.6 pKi 37
pKi 8.2 – 9.6 [37]
methysergide Hs Antagonist 8.6 – 9.1 pKi 19,37
pKi 8.6 – 9.1 [19,37]
metergoline Hs Inverse agonist 8.8 pKi 37
pKi 8.8 [37]
mianserin Hs Inverse agonist 8.3 – 9.2 pKi 21,37,47
pKi 8.3 – 9.2 [21,37,47]
SB 221284 Hs Antagonist 8.7 pKi 37
pKi 8.7 [37]
amoxapine Rn Antagonist 8.7 pKi 60
pKi 8.7 [60]
zotepine Hs Inverse agonist 8.6 pKi 33
pKi 8.6 [33]
SB 242084 Hs Antagonist 8.2 – 9.0 pKi 35,37
pKi 8.2 – 9.0 [35,37]
methiothepin Hs Inverse agonist 8.4 pKi 37
pKi 8.4 [37]
amitriptyline Rn Antagonist 8.4 pKi 60
pKi 8.4 [60]
RS-102221 Rn Antagonist 8.4 pKi 5
pKi 8.4 [5]
RS-102221 Hs Antagonist 8.3 – 8.4 pKi 5,37
pKi 8.3 – 8.4 [5,37]
tiospirone Hs Inverse agonist 8.3 pKi 33
pKi 8.3 [33]
olanzapine Hs Inverse agonist 8.1 – 8.2 pKi 33,39
pKi 8.1 – 8.2 [33,39]
ziprasidone Hs Inverse agonist 7.9 – 8.4 pKi 33,39
pKi 7.9 – 8.4 [33,39]
SDZ SER-082 Hs Antagonist 8.1 pKi 37
pKi 8.1 [37]
clozapine Hs Inverse agonist 7.4 – 8.7 pKi 21,33,37,39,44,70
pKi 7.4 – 8.7 [21,33,37,39,44,70]
cyamemazine Hs Antagonist 7.9 pKi 29
pKi 7.9 [29]
loxapine Hs Inverse agonist 7.8 – 8.0 pKi 33,39
pKi 7.8 – 8.0 [33,39]
chlorpromazine Hs Antagonist 7.6 – 8.2 pKi 33,39
pKi 7.6 – 8.2 [33,39]
SB 206553 Hs Antagonist 7.8 – 7.9 pKi 34,37
pKi 7.8 – 7.9 [34,37]
SB 215505 Hs Antagonist 7.7 pKi 63
pKi 7.7 [63]
EGIS-7625 Hs Antagonist 7.7 pKi 38
pKi 7.7 [38]
volinanserin Hs Antagonist 7.5 – 7.7 pKi 37,63
pKi 7.5 – 7.7 [37,63]
risperidone Hs Inverse agonist 7.5 – 7.6 pKi 33,39
pKi 7.5 – 7.6 [33,39]
mirtazapine Hs Antagonist 7.41 pKi 20
pKi 7.41 (Ki 3.9x10-8 M) [20]
sarpogrelate Hs Antagonist 7.4 pKi 61
pKi 7.4 [61]
xanomeline Hs Antagonist 7.4 pKi 71
pKi 7.4 [71]
terguride Hs Antagonist 7.3 pKi 46
pKi 7.3 [46]
fluoxetine Rn Antagonist 7.3 pKi 64
pKi 7.3 [64]
thioridazine Hs Antagonist 7.2 – 7.3 pKi 33,39
pKi 7.2 – 7.3 [33,39]
ketanserin Hs Antagonist 6.8 – 7.5 pKi 8,21,37,61
pKi 6.8 – 7.5 [8,21,37,61]
S33084 Hs Antagonist 7.1 pKi 45
pKi 7.1 [45]
LY334362 Hs Antagonist 7.0 pKi 8
pKi 7.0 [8]
apomorphine Hs Antagonist 7.0 pKi 46
pKi 7.0 [46]
perphenazine Hs Antagonist 6.9 pKi 39
pKi 6.9 [39]
MDL-11,939 Hs Antagonist 6.6 pKi 37
pKi 6.6 [37]
trazodone Hs Antagonist 6.6 pKi 37
pKi 6.6 [37]
trazodone Rn Antagonist 6.4 – 6.7 pKi 60,64
pKi 6.4 – 6.7 [60,64]
norfluoxetine Rn Antagonist 6.5 pKi 64
pKi 6.5 [64]
roxindole Hs Antagonist 6.5 pKi 46
pKi 6.5 [46]
trifluoperazine Hs Antagonist 6.4 pKi 39
pKi 6.4 [39]
RS-127445 Hs Antagonist 6.3 pKi 37
pKi 6.3 [37]
agomelatine Hs Antagonist 6.2 pKi 43
pKi 6.2 [43]
MPDT Rn Antagonist 6.2 pKi 28
pKi 6.2 [28]
duloxetine Hs Antagonist 6.0 pKi 11
pKi 6.0 [11]
SB 224289 Hs Antagonist 5.7 – 6.2 pKi 37,66
pKi 6.2 [66]
pKi 5.7 [37]
spiperone Hs Antagonist 5.6 – 6.2 pKi 21,33,37
pKi 5.6 – 6.2 [21,33,37]
spiramide Hs Antagonist 5.8 pKi 37
pKi 5.8 [37]
SB 204741 Hs Antagonist 5.6 pKi 37
pKi 5.6 [37]
AC-90179 Hs Inverse agonist 5.5 pKi 54
pKi 5.5 [54]
SB 243213 Hs Antagonist 9.0 pEC50 7
pEC50 9.0 [7]
View species-specific antagonist tables
Antagonist Comments
Mirtazapine is an antagonist of α2-adrenoceptors and serotonin 5-HT2a and 5-HT2c receptors.
Primary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
References:  16-17,40
Secondary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
References:  40
Tissue Distribution
Resting lymphocytes.
Species:  Human
Technique:  RT-PCR.
References:  41
Lumbar dorsal root ganglia.
Species:  Rat
Technique:  RT-PCR.
References:  55
CNS: choroid plexuses, retrosplenial, piriform and entorhinal cortex, anterior olfactory nucleus, lateral septal nucleus, subthalamic nucleus, amygdala, subiculum and ventral part of CA3, lateral habenula, substantia nigra pars compacta, several brainstem nuclei and the whole grey matter of the spinal cord.
Species:  Rat
Technique:  in situ hybridisation.
References:  56
Medulla oblongata and grey matter of the spinal cord.
Species:  Rat
Technique:  in situ hybridisation.
References:  25
GABAergic cells of the anterior raphe nuclei.
Species:  Rat
Technique:  Double in situ hybridisation.
References:  67
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Measurement of IP and IP3 levels in AV12 cells transfected with the mouse 5-HT2C receptor.
Species:  Mouse
Tissue:  AV12 cells.
Response measured:  IP and IP3 production.
References:  40
Measurement of cAMP levels in AV12 cells transfected with the mouse 5-HT2C receptor.
Species:  Mouse
Tissue:  AV12 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  40
Measurement of cAMP levels in AV12 cells transfected with the human 5-HT2C receptor.
Species:  Human
Tissue:  AV12 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  40
Measurement of intracellular Ca2+ levels using a fluorometric imaging plate reader (FLIPR) in CHO-K1 cells transfected with the human 5-HT2C receptor.
Species:  Human
Tissue:  CHO-K1 cells.
Response measured:  Increase in intracellular [Ca2+].
References:  57
Measurement of phosphatidylinositol turnover in rat choroid plexus.
Species:  Rat
Tissue:  Choroid plexus.
Response measured:  Stimulation of phosphatidylinositol turnover.
References:  16
Physiological Functions
Analgesia.
Species:  Mouse
Tissue:  In vivo.
References:  13
Anxiety.
Species:  Rat
Tissue:  In vivo.
References:  1,27
Hyperlocomotion.
Species:  Rat
Tissue:  In vivo.
References:  24
Decrease in food intake.
Species:  Rat
Tissue:  In vivo.
References:  24
Regulation of sleep.
Species:  Mouse
Tissue:  In vivo.
References:  26
Regulation of the response to repeated stress.
Species:  Mouse
Tissue:  In vivo.
References:  15
Physiological Consequences of Altering Gene Expression
5-HT2C receptor knockout mice have increased susceptibility to audiogenic epileptic seizures.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  6
5-HT2C receptor knockout mice exhibit increased food intake followed by the development of late-onset obesity. They also have reduced β3-adrenoceptor levels in white adipose tissue, linked to enhanced adiposity.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  52
5-HT2C receptor knockout mice exhibit abnormal wakefulness and rapid eye movement sleep (REM).
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  26
5-HT2C receptor knockout mice display symptoms of obsessive-compulsive disorder (OCD).
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  14
5-HT2C receptor knockout mice exhibit hyperresponsiveness to repeated stress.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  15
Young 5-HT2C receptor knockout mice exhibit increased activity levels which compensates for the parallel increase in food intake. However in older knockout mice, reductions in the energy cost of physical activity lead to an inability to compensate for increased food intake and late-onset obesity is observed.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  51
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Htr2ctm1Knk Htr2ctm1Knk/Y
B6.Cg-Htr2c
MGI:96281  MP:0009642 abnormal blood homeostasis PMID: 19036977 
Htr2ctm1Knk Htr2ctm1Knk/Y
B6.Cg-Htr2c
MGI:96281  MP:0005535 abnormal body temperature PMID: 19036977 
Htr2ctm1Knk Htr2ctm1Knk/Y
B6.Cg-Htr2c
MGI:96281  MP:0005266 abnormal metabolism PMID: 19036977 
Htr2ctm1.1Eme Htr2ctm1.1Eme/Y
involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6
MGI:96281  MP:0001492 abnormal pilomotor reflex PMID: 20394819 
Htr2ctm1Jul Htr2ctm1Jul/Y
B6.129S-Htr2c
MGI:96281  MP:0003638 abnormal response/metabolism to endogenous compounds PMID: 9771748 
Htr2ctm1Jul Htr2ctm1Jul/Y
B6.129S-Htr2c
MGI:96281  MP:0001413 abnormal response to new environment PMID: 9844009 
Htr2ctm1Jul Htr2ctm1Jul/Y
B6.129S-Htr2c
MGI:96281  MP:0001463 abnormal spatial learning PMID: 9844009 
Htr2ctm1Jul Htr2ctm1Jul/Y
B6.129S-Htr2c
MGI:96281  MP:0008752 abnormal tumor necrosis factor level PMID: 9771748 
Htr2ctm1Knk Htr2ctm1Knk/Htr2ctm1Knk
B6.Cg-Htr2c
MGI:96281  MP:0001258 decreased body length PMID: 19036977 
Htr2ctm1Knk Htr2ctm1Knk/Y
B6.Cg-Htr2c
MGI:96281  MP:0001258 decreased body length PMID: 19036977 
Htr2ctm1.1Eme Htr2ctm1.1Eme/Y
involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6
MGI:96281  MP:0001258 decreased body length PMID: 20394819 
Htr2ctm1Knk Htr2ctm1Knk/Htr2ctm1Knk
B6.Cg-Htr2c
MGI:96281  MP:0006086 decreased body mass index PMID: 19036977 
Htr2ctm1Knk Htr2ctm1Knk/Y
B6.Cg-Htr2c
MGI:96281  MP:0006086 decreased body mass index PMID: 19036977 
Htr2ctm1Knk|Mc4rtm1Lowl Htr2ctm1Knk/Y,Mc4rtm1Lowl/Mc4rtm1Lowl
involves: 129S4/SvJae * C57BL/6
MGI:96281  MGI:99457  MP:0006086 decreased body mass index PMID: 19036977 
Htr2ctm1Knk Htr2ctm1Knk/Htr2ctm1Knk
B6.Cg-Htr2c
MGI:96281  MP:0001262 decreased body weight PMID: 19036977 
Htr2ctm1Knk Htr2ctm1Knk/Y
B6.Cg-Htr2c
MGI:96281  MP:0001262 decreased body weight PMID: 19036977 
Htr2ctm1.1Eme Htr2ctm1.1Eme/Y
involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6
MGI:96281  MP:0001262 decreased body weight PMID: 20394819 
Htr2c+|Htr2ctm1.1Eme Htr2ctm1.1Eme/Htr2c+
involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6
MGI:96281  MP:0001262 decreased body weight PMID: 20394819 
Htr2ctm1.1Eme Htr2ctm1.1Eme/Htr2ctm1.1Eme
involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6
MGI:96281  MP:0001262 decreased body weight PMID: 20394819 
Htr2ctm1Knk Htr2ctm1Knk/Y
B6.Cg-Htr2c
MGI:96281  MP:0001780 decreased brown adipose tissue amount PMID: 19036977 
Htr2ctm1Knk Htr2ctm1Knk/Y
B6.Cg-Htr2c
MGI:96281  MP:0005179 decreased circulating cholesterol level PMID: 19036977 
Htr2ctm1Knk Htr2ctm1Knk/Y
B6.Cg-Htr2c
MGI:96281  MP:0005560 decreased circulating glucose level PMID: 19036977 
Htr2ctm1Knk Htr2ctm1Knk/Y
B6.Cg-Htr2c
MGI:96281  MP:0002727 decreased circulating insulin level PMID: 19036977 
Htr2ctm1Knk Htr2ctm1Knk/Y
B6.Cg-Htr2c
MGI:96281  MP:0004701 decreased circulating insulin-like growth factor I level PMID: 19036977 
Htr2ctm1Knk Htr2ctm1Knk/Y
B6.Cg-Htr2c
MGI:96281  MP:0005668 decreased circulating leptin level PMID: 19036977 
Htr2ctm1Knk Htr2ctm1Knk/Y
B6.Cg-Htr2c
MGI:96281  MP:0002644 decreased circulating triglyceride level PMID: 19036977 
Htr2ctm1.1Eme Htr2ctm1.1Eme/Y
involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6