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5-HT2C

Previous and Unofficial Names
Names References
5-HT1C 231
Structural Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Name Reference
Human 7 458 Xq24 HTR2C 227
Rat 7 460 Xq34-q35.1 Htr2c 226
Mouse 7 459 X D-F4 Htr2c 162,228
Contents:
Previous and Unofficial Names
Structural Information
Database Links
Agonists
Antagonists
Transduction Mechanisms
Tissue Distribution
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Biologically Significant Variants
Receptor Comments
Database Links
ChEMBL Target 108 (Hs), 11864 (Mm), 12689 (Rn)
Ensembl ENSG00000147246 (Hs), ENSMUSG00000041380 (Mm), ENSRNOG00000030877 (Rn)
Entrez Gene 3358 (Hs), 15560 (Mm), 25187 (Rn)
GeneCards HTR2C (Hs)
HomoloGene 20242 (Hs)
OMIM 312861 (Hs)
PharmGKB Gene PA194 (Hs)
Protein Ontology (PRO) PRO:000001168 (Hs)
RefSeq Nucleotide NM_000868 (Hs), NM_008312 (Mm), NM_012765 (Rn)
RefSeq Protein NP_000859 (Hs), NP_032338 (Mm), NP_036897 (Rn)
UniGene Hs. 149037 (Hs)
UniProt P28335 (Hs), P34968 (Mm), P08909 (Rn)
Wikipedia 5-HT2C
Search for 3D structures on the PDB
Search using keywords: 5-Hydroxytryptamine receptors 5-HT2C Search using accession numbers: P08909 || P28335 || P34968
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 62
[125I]DOI Hs Full agonist 8.7 – 9.0 pKd 253
YM348 Hs Full agonist 9.0 pKi 255
ergotamine Hs Partial agonist 8.7 pKi 182
methysergide Rn Partial agonist 8.7 pKi 190
(+)-LSD Hs Full agonist 8.2 – 9.0 pKi 182,253
AL-37350A Hs Full agonist 8.5 pKi 186
(R)-DOI Hs Full agonist 8.4 pKi 186
LSD Hs Full agonist 8.2 – 8.6 pKi 254
methylergonovine Hs Full agonist 8.3 pKi 182
VER-3323 Hs Full agonist 8.2 pKi 182
lisuride Hs Partial agonist 8.0 – 8.3 pKi 69,254
(+)-DOI Hs Full agonist 8.1 pKi 182
org 37684 Hs Full agonist 8.1 pKi 182
(R)-DOI Hs Full agonist 7.4 – 8.7 pKi 182,192,253
(+)-lisuride Hs Partial agonist 7.9 – 8.1 pKi 253
Ro 60-0175 Hs Full agonist 7.7 – 8.2 pKi 182,255
DOI Hs Full agonist 7.2 – 8.6 pKi 192,223,254
ergotamine Rn Partial agonist 7.9 pKi 190
methylergonovine Rn Full agonist 7.9 pKi 190
DOB Hs Full agonist 6.8 – 8.9 pKi 182,192,254
org 12962 Hs Full agonist 7.8 pKi 182
α-methyl-5-HT Hs Full agonist 6.9 – 8.6 pKi 182,253
5-HT Hs Full agonist 6.8 – 8.6 pKi 182,186,253-255
S 16924 Hs Full agonist 7.7 pKi 66
aripiprazole Hs Full agonist 7.6 pKi 193
m-CPP Hs Partial agonist 6.5 – 8.5 pKi 182,192,223,253-255
WAY-163909 Hs Full agonist 6.7 – 8.0 pKi 257
5-HT Rn Full agonist 6.7 – 7.9 pKi 190,256
5-MeOT Hs Full agonist 6.7 – 7.8 pKi 254
m-CPP Rn Partial agonist 7.2 pKi 190
TFMPP Hs Full agonist 6.5 – 7.8 pKi 182,254
BW723C86 Hs Full agonist 6.9 – 7.1 pKi 182,223
GR-127935 Hs Partial agonist 7.0 pKi 58
RU 24969 Hs Full agonist 6.8 pKi 182
SB 216641 Hs Partial agonist 6.8 pKi 58
quipazine Hs Full agonist 5.9 – 7.3 pKi 182,253-254
5-MeO-DMT Hs Full agonist 6.2 – 7.0 pKi 253
DOB Rn Full agonist 6.6 pKi 256
oxymetazoline Hs Full agonist 6.3 – 6.8 pKi 253
pergolide Hs Partial agonist 6.5 pKi 69
tryptamine Hs Full agonist 5.6 – 7.2 pKi 182,254
5-MeOT Rn Full agonist 6.3 pKi 256
MK-212 Hs Full agonist 5.6 – 7.0 pKi 182,223,254
BRL-15572 Hs Partial agonist 6.2 pKi 58
cabergoline Hs Full agonist 6.2 pKi 69
bromocriptine Hs Partial agonist 6.1 pKi 69
5-CT Hs Full agonist 5.2 – 6.7 pKi 182,254
8-OH-DPAT Hs Full agonist 5.6 pKi 182
CGS-12066 Hs Full agonist 5.6 pKi 182
LY344864 Hs Full agonist 5.5 pKi 64
SL65.0155 Hs Partial agonist 5.3 pKi 67
quinpirole Hs Full agonist 5.0 – 5.5 pKi 69,182
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 8.7 – 9.3 pKd 202,253
methysergide Rn Antagonist 9.3 pKi 256
mesulergine Rn Inverse agonist 9.2 pKi 256
mianserin Rn Antagonist 8.8 – 9.4 pKi 204,256
sertindole Hs Inverse agonist 9.0 – 9.2 pKi 193,245
SB 228357 Hs Antagonist 9.0 – 9.1 pKi 197,200
mesulergine Hs Inverse agonist 8.7 – 9.3 pKi 55,182,195
ritanserin Hs Antagonist 8.2 – 9.6 pKi 182
methysergide Hs Antagonist 8.6 – 9.1 pKi 182,254
metergoline Hs Inverse agonist 8.8 pKi 182
mianserin Hs Inverse agonist 8.3 – 9.2 pKi 54,182,253
amoxapine Rn Antagonist 8.7 pKi 204
SB 221284 Hs Antagonist 8.7 pKi 182
SB 242084 Hs Antagonist 8.2 – 9.0 pKi 182,201
zotepine Hs Inverse agonist 8.6 pKi 245
amitriptyline Rn Antagonist 8.4 pKi 204
methiothepin Hs Inverse agonist 8.4 pKi 182
RS-102221 Rn Antagonist 8.4 pKi 198
RS-102221 Hs Antagonist 8.3 – 8.4 pKi 182,198
tiospirone Hs Inverse agonist 8.3 pKi 245
olanzapine Hs Inverse agonist 8.1 – 8.2 pKi 193,245
ziprasidone Hs Inverse agonist 7.9 – 8.4 pKi 193,245
SDZ SER-082 Hs Antagonist 8.1 pKi 182
clozapine Hs Inverse agonist 7.4 – 8.7 pKi 66,182,193-194,245,253
cyamemazine Hs Antagonist 7.9 pKi 55
loxapine Hs Inverse agonist 7.8 – 8.0 pKi 193,245
chlorpromazine Hs Antagonist 7.6 – 8.2 pKi 193,245
SB 206553 Hs Antagonist 7.8 – 7.9 pKi 182,199
EGIS-7625 Hs Antagonist 7.7 pKi 195
SB 215505 Hs Antagonist 7.7 pKi 197
MDL-100,907 Hs Antagonist 7.5 – 7.7 pKi 182,197
risperidone Hs Inverse agonist 7.5 – 7.6 pKi 193,245
sarpogrelate Hs Antagonist 7.4 pKi 202
xanomeline Hs Antagonist 7.4 pKi 73
fluoxetine Rn Antagonist 7.3 pKi 190
terguride Hs Antagonist 7.3 pKi 69
thioridazine Hs Antagonist 7.2 – 7.3 pKi 193,245
ketanserin Hs Antagonist 6.8 – 7.5 pKi 182,196,202,253
S33084 Hs Antagonist 7.1 pKi 75
apomorphine Hs Antagonist 7.0 pKi 69
LY334362 Hs Antagonist 7.0 pKi 196
perphenazine Hs Antagonist 6.9 pKi 193
MDL-11,939 Hs Antagonist 6.6 pKi 182
trazodone Hs Antagonist 6.6 pKi 182
trazodone Rn Antagonist 6.4 – 6.7 pKi 190,204
norfluoxetine Rn Antagonist 6.5 pKi 190
roxindole Hs Antagonist 6.5 pKi 69
trifluoperazine Hs Antagonist 6.4 pKi 193
RS-127445 Hs Antagonist 6.3 pKi 182
agomelatine Hs Antagonist 6.2 pKi 203
MPDT Rn Antagonist 6.2 pKi 59
SB 224289 Hs Antagonist 6.2 pKi 128
duloxetine Hs Antagonist 6.0 pKi 205
spiperone Hs Antagonist 5.6 – 6.2 pKi 182,245,253
AMI-193 Hs Antagonist 5.8 pKi 182
SB 224289 Hs Antagonist 5.7 pKi 182
SB 204741 Hs Antagonist 5.6 pKi 182
AC-90179 Hs Inverse agonist 5.5 pKi 64
SB 243213 Hs Antagonist 9.0 pEC50 200
View species-specific antagonist tables

Explore drug-target interactions for this set of compounds using iPHACE

Primary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
References:  165,167,230
Secondary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
References:  167
Tissue Distribution
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:  169
Medulla oblongata and grey matter of the spinal cord.
Species:  Rat
Technique:  in situ hybridisation.
References:  174
Resting lymphocytes.
Species:  Human
Technique:  RT-PCR.
References:  247
Lumbar dorsal root ganglia.
Species:  Rat
Technique:  RT-PCR.
References:  33
GABAergic cells of the anterior raphe nuclei.
Species:  Rat
Technique:  Double in situ hybridisation.
References:  248
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:  167
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:  167
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:  167
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:  168
Measurement of phosphatidylinositol turnover in rat choroid plexus.
Species:  Rat
Tissue:  Choroid plexus.
Response measured:  Stimulation of phosphatidylinositol turnover.
References:  230
Physiological Functions
Analgesia.
Species:  Mouse
Tissue:  In vivo.
References:  249
Anxiety.
Species:  Rat
Tissue:  In vivo.
References:  250-251
Hyperlocomotion.
Species:  Rat
Tissue:  In vivo.
References:  252
Decrease in food intake.
Species:  Rat
Tissue:  In vivo.
References:  252
Regulation of sleep.
Species:  Mouse
Tissue:  In vivo.
References:  234
Regulation of the response to repeated stress.
Species:  Mouse
Tissue:  In vivo.
References:  236
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:  232
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:  233
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:  234
5-HT2C receptor knockout mice display symptoms of obsessive-compulsive disorder (OCD).
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  235
5-HT2C receptor knockout mice exhibit hyperresponsiveness to repeated stress.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  236
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:  237
Biologically Significant Variants
A -759T allele within the promoter region of the HTR2C gene has a higher transcriptional activity than the more common -759C allele. Hence, a higher frequency of the -759T allele leads to higher basal expression of 5-HT2C receptors and subsequent protection against antipsychotic-induced weight gain.
Type:  Single nucleotide polymorphism.
Species:  Human
References:  238
RNA editing of the 5-HT2C receptor results in the expression of 14 different isoforms in the human brain. The isoforms have different levels of constitutive activity, with the unedited receptor displaying the highest degree and the fully edited receptor displaying no constitutive activity. RNA editing alters receptor-mediated activation of G13 and arachidonic acid production. 5-HT has lower affinity and potency for the fully edited isoform. Atypical antipsychotic drugs display inverse agonist activity at the unedited isoform of the human 5-HT2C receptor.
Type:  RNA editing.
Species:  Human
References:  239-246
Receptor Comments
A non-functional short (248aa) splice-variant of the h 5-HT2C receptor has been described [229].

To cite this receptor data page, please use the following:

Rodrigo Andrade, Nicholas M. Barnes, Gordon Baxter, Joel Bockaert, Theresa Branchek, Marlene L. Cohen, Aline Dumuis, Richard M. Eglen, Manfred Göthert, Mark Hamblin, Michel Hamon, Paul R. Hartig, René Hen, Katharine Herrick-Davis, Rebecca Hills, Daniel Hoyer, Patrick P. A. Humphrey, Klaus Peter Latté, Luc Maroteaux, Graeme R. Martin, Derek N. Middlemiss, Ewan Mylecharane, Stephen J. Peroutka, Pramod R. Saxena, Andrew Sleight, Carlos M. Villalon, Frank Yocca.
5-Hydroxytryptamine receptors: 5-HT2C. Last modified on 2010-06-30. Accessed on 2010-09-03. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=8.


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