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 69
Mouse 7 459 X D-F4 Htr2c 5-hydroxytryptamine (serotonin) receptor 2C 24,73
Rat 7 460 Xq34-q35.1 Htr2c 5-hydroxytryptamine (serotonin) receptor 2C, G protein-coupled 5
Previous and Unofficial Names
Names References
5-HT1C 54
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 Ligands
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 4
pKd 9.1 [4]
[125I]DOI Hs Full agonist 8.7 – 9.0 pKd 22
pKd 8.7 – 9.0 [22]
YM348 Hs Full agonist 9.0 pKi 37
pKi 9.0 [37]
ergotamine Hs Partial agonist 8.7 pKi 38
pKi 8.7 [38]
methysergide Rn Partial agonist 8.7 pKi 65
pKi 8.7 [65]
(+)-LSD Hs Full agonist 8.2 – 9.0 pKi 22,38
pKi 8.2 – 9.0 [22,38]
AL-37350A Hs Full agonist 8.5 pKi 43
pKi 8.5 [43]
LSD Hs Full agonist 8.2 – 8.6 pKi 20
pKi 8.2 – 8.6 [20]
methylergonovine Hs Full agonist 8.3 pKi 38
pKi 8.3 [38]
VER-3323 Hs Full agonist 8.2 pKi 38
pKi 8.2 [38]
lisuride Hs Partial agonist 7.9 – 8.3 pKi 20,22,47
pKi 7.9 – 8.3 [20,22,47]
org 37684 Hs Full agonist 8.1 pKi 38
pKi 8.1 [38]
(+)-DOI Hs Full agonist 8.1 pKi 38
pKi 8.1 [38]
(R)-DOI Hs Full agonist 7.4 – 8.7 pKi 22,38,43,50
pKi 8.4 [43]
pKi 7.4 – 8.7 [22,38,50]
Ro 60-0175 Hs Full agonist 7.7 – 8.2 pKi 37-38
pKi 7.7 – 8.2 [37-38]
DOI Hs Full agonist 7.2 – 8.6 pKi 20,50,66
pKi 7.2 – 8.6 [20,50,66]
ergotamine Rn Partial agonist 7.9 pKi 65
pKi 7.9 [65]
methylergonovine Rn Full agonist 7.9 pKi 65
pKi 7.9 [65]
DOB Hs Full agonist 6.8 – 8.9 pKi 20,38,50
pKi 6.8 – 8.9 [20,38,50]
lorcaserin Hs Full agonist 7.8 pKi 70
pKi 7.8 [70]
org 12962 Hs Full agonist 7.8 pKi 38
pKi 7.8 [38]
α-methyl-5-HT Hs Full agonist 6.9 – 8.6 pKi 22,38
pKi 6.9 – 8.6 [22,38]
5-HT Hs Full agonist 6.8 – 8.6 pKi 20,22,37-38,43
pKi 6.8 – 8.6 [20,22,37-38,43]
S 16924 Hs Full agonist 7.7 pKi 45
pKi 7.7 [45]
aripiprazole Hs Full agonist 7.6 pKi 40
pKi 7.6 [40]
m-CPP Hs Partial agonist 6.5 – 8.5 pKi 20,22,37-38,50,66
pKi 6.5 – 8.5 [20,22,37-38,50,66]
WAY-163909 Hs Full agonist 6.7 – 8.0 pKi 19
pKi 6.7 – 8.0 [19]
5-HT Rn Full agonist 6.7 – 7.9 pKi 32,65
pKi 6.7 – 7.9 [32,65]
5-MeOT Hs Full agonist 6.7 – 7.8 pKi 20
pKi 6.7 – 7.8 [20]
m-CPP Rn Partial agonist 7.2 pKi 65
pKi 7.2 [65]
TFMPP Hs Full agonist 6.5 – 7.8 pKi 20,38
pKi 6.5 – 7.8 [20,38]
GR-127935 Hs Partial agonist 7.0 pKi 59
pKi 7.0 [59]
BW723C86 Hs Full agonist 6.9 – 7.1 pKi 38,66
pKi 6.9 – 7.1 [38,66]
SB 216641 Hs Partial agonist 6.8 pKi 59
pKi 6.8 [59]
RU 24969 Hs Full agonist 6.8 pKi 38
pKi 6.8 [38]
quipazine Hs Full agonist 5.9 – 7.3 pKi 20,22,38
pKi 5.9 – 7.3 [20,22,38]
5-MeO-DMT Hs Full agonist 6.2 – 7.0 pKi 22
pKi 6.2 – 7.0 [22]
DOB Rn Full agonist 6.6 pKi 32
pKi 6.6 [32]
oxymetazoline Hs Full agonist 6.3 – 6.8 pKi 22
pKi 6.3 – 6.8 [22]
pergolide Hs Partial agonist 6.5 pKi 47
pKi 6.5 [47]
tryptamine Hs Full agonist 5.6 – 7.2 pKi 20,38
pKi 5.6 – 7.2 [20,38]
5-MeOT Rn Full agonist 6.3 pKi 32
pKi 6.3 [32]
MK-212 Hs Full agonist 5.6 – 7.0 pKi 20,38,66
pKi 5.6 – 7.0 [20,38,66]
cabergoline Hs Full agonist 6.2 pKi 47
pKi 6.2 [47]
BRL-15572 Hs Partial agonist 6.2 pKi 59
pKi 6.2 [59]
bromocriptine Hs Partial agonist 6.1 pKi 47
pKi 6.1 [47]
5-CT Hs Full agonist 5.2 – 6.7 pKi 20,38
pKi 5.2 – 6.7 [20,38]
CGS-12066 Hs Full agonist 5.6 pKi 38
pKi 5.6 [38]
8-OH-DPAT Hs Full agonist 5.6 pKi 38
pKi 5.6 [38]
LY344864 Hs Full agonist 5.5 pKi 55
pKi 5.5 [55]
SL65.0155 Hs Partial agonist 5.3 pKi 49
pKi 5.3 [49]
quinpirole Hs Full agonist 5.0 – 5.5 pKi 38,47
pKi 5.0 – 5.5 [38,47]
lorcaserin Hs Full agonist 8.1 pEC50 70
pEC50 8.1 [70]
[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 22,62
pKd 9.3 – 8.7 (Kd 5x10-10 – 2.2x10-9 M) [22,62]
methysergide Rn Antagonist 9.3 pKi 32
pKi 9.3 [32]
mesulergine Rn Inverse agonist 9.2 pKi 32
pKi 9.2 [32]
mianserin Rn Antagonist 8.8 – 9.4 pKi 32,61
pKi 8.8 – 9.4 [32,61]
sertindole Hs Inverse agonist 9.0 – 9.2 pKi 34,40
pKi 9.0 – 9.2 [34,40]
SB 228357 Hs Antagonist 9.0 – 9.1 pKi 8,64
pKi 9.0 – 9.1 [8,64]
FR260010 Hs Antagonist 9.0 pKi 31
pKi 9.0 (Ki 1.1x10-9 M) [31]
mesulergine Hs Inverse agonist 8.7 – 9.3 pKi 30,38-39
pKi 8.7 – 9.3 [30,38-39]
ritanserin Hs Antagonist 8.2 – 9.6 pKi 38
pKi 8.2 – 9.6 [38]
methysergide Hs Antagonist 8.6 – 9.1 pKi 20,38
pKi 8.6 – 9.1 [20,38]
metergoline Hs Inverse agonist 8.8 pKi 38
pKi 8.8 [38]
mianserin Hs Inverse agonist 8.3 – 9.2 pKi 22,38,48
pKi 8.3 – 9.2 [22,38,48]
SB 221284 Hs Antagonist 8.7 pKi 38
pKi 8.7 [38]
amoxapine Rn Antagonist 8.7 pKi 61
pKi 8.7 [61]
zotepine Hs Inverse agonist 8.6 pKi 34
pKi 8.6 [34]
SB 242084 Hs Antagonist 8.2 – 9.0 pKi 36,38
pKi 8.2 – 9.0 [36,38]
methiothepin Hs Inverse agonist 8.4 pKi 38
pKi 8.4 [38]
amitriptyline Rn Antagonist 8.4 pKi 61
pKi 8.4 [61]
RS-102221 Rn Antagonist 8.4 pKi 6
pKi 8.4 [6]
RS-102221 Hs Antagonist 8.3 – 8.4 pKi 6,38
pKi 8.3 – 8.4 [6,38]
tiospirone Hs Inverse agonist 8.3 pKi 34
pKi 8.3 [34]
olanzapine Hs Inverse agonist 8.1 – 8.2 pKi 34,40
pKi 8.1 – 8.2 [34,40]
ziprasidone Hs Inverse agonist 7.9 – 8.4 pKi 34,40
pKi 7.9 – 8.4 [34,40]
SDZ SER-082 Hs Antagonist 8.1 pKi 38
pKi 8.1 [38]
clozapine Hs Inverse agonist 7.4 – 8.7 pKi 22,34,38,40,45,71
pKi 7.4 – 8.7 [22,34,38,40,45,71]
cyamemazine Hs Antagonist 7.9 pKi 30
pKi 7.9 [30]
loxapine Hs Inverse agonist 7.8 – 8.0 pKi 34,40
pKi 7.8 – 8.0 [34,40]
chlorpromazine Hs Antagonist 7.6 – 8.2 pKi 34,40
pKi 7.6 – 8.2 [34,40]
SB 206553 Hs Antagonist 7.8 – 7.9 pKi 35,38
pKi 7.8 – 7.9 [35,38]
SB 215505 Hs Antagonist 7.7 pKi 64
pKi 7.7 [64]
EGIS-7625 Hs Antagonist 7.7 pKi 39
pKi 7.7 [39]
volinanserin Hs Antagonist 7.5 – 7.7 pKi 38,64
pKi 7.5 – 7.7 [38,64]
risperidone Hs Inverse agonist 7.5 – 7.6 pKi 34,40
pKi 7.5 – 7.6 [34,40]
mirtazapine Hs Antagonist 7.41 pKi 21
pKi 7.41 (Ki 3.9x10-8 M) [21]
pKi 7.41 (Ki 3.9x10-8 M) [21]
sarpogrelate Hs Antagonist 7.4 pKi 62
pKi 7.4 [62]
xanomeline Hs Antagonist 7.4 pKi 72
pKi 7.4 [72]
terguride Hs Antagonist 7.3 pKi 47
pKi 7.3 [47]
fluoxetine Rn Antagonist 7.3 pKi 65
pKi 7.3 [65]
thioridazine Hs Antagonist 7.2 – 7.3 pKi 34,40
pKi 7.2 – 7.3 [34,40]
ketanserin Hs Antagonist 6.8 – 7.5 pKi 9,22,38,62
pKi 6.8 – 7.5 [9,22,38,62]
S33084 Hs Antagonist 7.1 pKi 46
pKi 7.1 [46]
LY334362 Hs Antagonist 7.0 pKi 9
pKi 7.0 [9]
apomorphine Hs Antagonist 7.0 pKi 47
pKi 7.0 [47]
perphenazine Hs Antagonist 6.9 pKi 40
pKi 6.9 [40]
vortioxetine Hs Antagonist 6.74 pKi 2
pKi 6.74 (Ki 1.8x10-7 M) [2]
glemanserin Hs Antagonist 6.6 pKi 38
pKi 6.6 [38]
trazodone Hs Antagonist 6.6 pKi 38
pKi 6.6 [38]
trazodone Rn Antagonist 6.4 – 6.7 pKi 61,65
pKi 6.4 – 6.7 [61,65]
norfluoxetine Rn Antagonist 6.5 pKi 65
pKi 6.5 [65]
roxindole Hs Antagonist 6.5 pKi 47
pKi 6.5 [47]
trifluoperazine Hs Antagonist 6.4 pKi 40
pKi 6.4 [40]
RS-127445 Hs Antagonist 6.3 pKi 38
pKi 6.3 [38]
agomelatine Hs Antagonist 6.2 pKi 44
pKi 6.2 [44]
MPDT Rn Antagonist 6.2 pKi 29
pKi 6.2 [29]
duloxetine Hs Antagonist 6.0 pKi 12
pKi 6.0 [12]
SB 224289 Hs Antagonist 5.7 – 6.2 pKi 38,67
pKi 6.2 [67]
pKi 5.7 [38]
spiperone Hs Antagonist 5.6 – 6.2 pKi 22,34,38
pKi 5.6 – 6.2 [22,34,38]
spiramide Hs Antagonist 5.8 pKi 38
pKi 5.8 [38]
SB 204741 Hs Antagonist 5.6 pKi 38
pKi 5.6 [38]
AC-90179 Hs Inverse agonist 5.5 pKi 55
pKi 5.5 [55]
SB 243213 Hs Antagonist 9.0 pEC50 8
pEC50 9.0 [8]
View species-specific antagonist tables
Antagonist Comments
Mirtazapine is an antagonist of α2-adrenoceptors and serotonin 5-HT2A and 5-HT2C receptors.
Mianserin has activity accross several families of GPCRs, including the histamine H1 receptor, 5-HT receptors and α-adrenoceptors, but may have additional actions. The 5-HT2A, 2B and 2C receptors have been tagged as the primary targets of this drug in view of their high affinity. This does not preclude clinically relevant actions at other molecular targets.
Primary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
References:  17-18,41
Secondary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
References:  41
Tissue Distribution
Resting lymphocytes.
Species:  Human
Technique:  RT-PCR.
References:  42
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:  57
Medulla oblongata and grey matter of the spinal cord.
Species:  Rat
Technique:  in situ hybridisation.
References:  26
Lumbar dorsal root ganglia.
Species:  Rat
Technique:  RT-PCR.
References:  56
GABAergic cells of the anterior raphe nuclei.
Species:  Rat
Technique:  Double in situ hybridisation.
References:  68
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:  41
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:  41
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:  41
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:  58
Measurement of phosphatidylinositol turnover in rat choroid plexus.
Species:  Rat
Tissue:  Choroid plexus.
Response measured:  Stimulation of phosphatidylinositol turnover.
References:  17
Physiological Functions
Analgesia.
Species:  Mouse
Tissue:  In vivo.
References:  14
Anxiety.
Species:  Rat
Tissue:  In vivo.
References:  1,28
Hyperlocomotion.
Species:  Rat
Tissue:  In vivo.
References:  25
Decrease in food intake.
Species:  Rat
Tissue:  In vivo.
References:  25
Regulation of sleep.
Species:  Mouse
Tissue:  In vivo.
References:  27
Regulation of the response to repeated stress.
Species:  Mouse
Tissue:  In vivo.
References:  16
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:  7
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:  53
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:  27
5-HT2C receptor knockout mice display symptoms of obsessive-compulsive disorder (OCD).
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  15
5-HT2C receptor knockout mice exhibit hyperresponsiveness to repeated stress.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  16
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.