5-HT<sub>6</sub> receptor | 5-Hydroxytryptamine receptors | IUPHAR/BPS Guide to PHARMACOLOGY

5-HT6 receptor

Target id: 11

Nomenclature: 5-HT6 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.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for 5-HT6 receptor in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 440 1p36-p35 HTR6 5-hydroxytryptamine receptor 6 21
Mouse 7 440 4 D3 Htr6 5-hydroxytryptamine (serotonin) receptor 6 20
Rat 7 436 5 Htr6 5-hydroxytryptamine receptor 6 28,38
Previous and Unofficial Names
5-HT6 | serotonin receptor 6 | ST-B17 | 5-hydroxytryptamine (serotonin) receptor 6, G protein-coupled
Database Links
Specialist databases
GPCRDB 5ht6r_human (Hs), 5ht6r_mouse (Mm), 5ht6r_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
5-hydroxytryptamine

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]LSD Hs Full agonist 8.7 pKd 5
pKd 8.7 (Kd 2x10-9 M) [5]
[3H]LSD Rn Full agonist 8.6 – 8.7 pKd 4,25
pKd 8.6 – 8.7 [4,25]
5-hydroxytryptamine Rn Full agonist 7.9 pKd 4
pKd 7.9 [4]
E6801 Hs Partial agonist 8.7 pKi 17
pKi 8.7 (Ki 1.9x10-9 M) [17]
WAY-181187 Hs Agonist 8.7 pKi 39
pKi 8.7 [39]
Lysergide Hs Full agonist 8.4 pKi 7
pKi 8.4 [7]
WAY-208466 Hs Agonist 8.3 pKi 3
pKi 8.3 (Ki 4.8x10-9 M) [3]
ergotamine Hs Full agonist 8.0 – 8.6 pKi 5,7
pKi 8.0 – 8.6 [5,7]
Lysergide Rn Full agonist 7.8 – 8.7 pKi 4,7
pKi 7.8 – 8.7 [4,7]
lisuride Hs Partial agonist 8.0 – 8.1 pKi 5,7
pKi 8.0 – 8.1 [5,7]
lisuride Rn Partial agonist 7.5 – 8.3 pKi 4,6-7,28
pKi 7.5 – 8.3 [4,6-7,28]
EMDT Hs Full agonist 7.8 pKi 14
pKi 7.8 [14]
ergotamine Rn Full agonist 7.0 – 8.6 pKi 4,6-7
pKi 7.0 – 8.6 [4,6-7]
5-MeOT Rn Full agonist 6.9 – 8.4 pKi 4,6,28
pKi 6.9 – 8.4 [4,6,28]
S 16924 Rn Full agonist 7.6 pKi 27
pKi 7.6 [27]
bromocriptine Hs Full agonist 7.5 pKi 21
pKi 7.5 [21]
bromocriptine Rn Partial agonist 7.5 pKi 6
pKi 7.5 [6]
pergolide Rn Full agonist 7.5 pKi 28
pKi 7.5 [28]
5-MeOT Hs Full agonist 7.4 pKi 21
pKi 7.4 [21]
lergotrile Rn Full agonist 7.4 pKi 28
pKi 7.4 [28]
5-hydroxytryptamine Rn Full agonist 6.6 – 7.9 pKi 4,6-7,28
pKi 6.6 – 7.9 [4,6-7,28]
dimethyltryptamine Hs Full agonist 7.2 pKi 21
pKi 7.2 [21]
5-hydroxytryptamine Hs Full agonist 6.8 – 7.5 pKi 5,7,21
pKi 6.8 – 7.5 [5,7,21]
1-naphthylpiperazine Rn Full agonist 7.0 pKi 28
pKi 7.0 [28]
5-MeO-DMT Rn Full agonist 6.9 pKi 6
pKi 6.9 [6]
5-benzyloxytryptamine Rn Full agonist 6.5 – 7.2 pKi 4,6,28
pKi 6.5 – 7.2 [4,6,28]
2-methyl-5-HT Rn Full agonist 6.2 – 7.3 pKi 4
pKi 6.2 – 7.3 [4]
DM-1451 Rn Full agonist 6.5 pKi 25
pKi 6.5 [25]
TFMPP Hs Full agonist 6.4 pKi 21
pKi 6.4 [21]
TFMPP Rn Full agonist 6.3 pKi 28
pKi 6.3 [28]
tryptamine Rn Full agonist 5.8 – 6.8 pKi 4,28
pKi 5.8 – 6.8 [4,28]
RU 24969 Hs Full agonist 6.2 pKi 21
pKi 6.2 [21]
OPC 4392 Rn Full agonist 6.2 pKi 25
pKi 6.2 [25]
5-CT Hs Full agonist 6.1 pKi 21
pKi 6.1 [21]
5-CT Rn Full agonist 5.5 – 6.7 pKi 4,6,28
pKi 5.5 – 6.7 [4,6,28]
LY 165,163 Rn Full agonist 6.1 pKi 28
pKi 6.1 [28]
CGS-12066 Rn Full agonist 6.1 pKi 28
pKi 6.1 [28]
BRL-15572 Hs Partial agonist 5.9 pKi 34
pKi 5.9 [34]
xanomeline Hs Full agonist 5.9 pKi 42
pKi 5.9 [42]
GR 127935 Hs Partial agonist 5.8 pKi 34
pKi 5.8 [34]
capeserod Hs Partial agonist 5.6 pKi 29
pKi 5.6 [29]
donitriptan Hs Partial agonist 5.6 pKi 18
pKi 5.6 [18]
m-chlorophenylpiperazine Rn Full agonist 5.6 pKi 28
pKi 5.6 [28]
α-methyl-5-HT Rn Full agonist 5.5 pKi 6
pKi 5.5 [6]
EMD-386088 Hs Agonist 8.1 pIC50 26
pIC50 8.1 (IC50 7.4x10-9 M) [26]
[3H]5-CT 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
[125I]SB258585 Hs Antagonist 9.0 pKd 16
pKd 9.0 (Kd 1x10-9 M) [16]
[3H]Ro 63-0563 Hs Antagonist 8.3 pKd 7
pKd 8.3 (Kd 5x10-9 M) [7]
[11C]GSK215083 Hs Antagonist 9.8 pKi 31
pKi 9.8 (Ki 1.6x10-10 M) [31]
intepirdine Hs Antagonist 9.8 pKi 23
pKi 9.8 (Ki 1.7x10-10 M) [23]
Description: HeLa cell membrane assay, displacing [3H]LSD
idalopirdine Hs Antagonist 9.1 pKi 23
pKi 9.1 (Ki 8.3x10-10 M) [23]
SB399885 Hs Antagonist 9.0 pKi 16
pKi 9.0 (Ki 1x10-9 M) [16]
zotepine Rn Inverse agonist 8.9 pKi 37
pKi 8.9 [37]
SB 271046 Hs Antagonist 8.9 pKi 10
pKi 8.9 (Ki 1.26x10-9 M) [10]
cerlapirdine Hs Antagonist 8.9 pKi 13
pKi 8.9 (Ki 1.3x10-9 M) [13]
methiothepin Hs Antagonist 8.2 – 9.4 pKi 5,7,21
pKi 8.2 – 9.4 [5,7,21]
SB258585 Hs Antagonist 8.5 pKi 15
pKi 8.5 [15]
SB357134 Hs Antagonist 8.5 pKi 11
pKi 8.5 [11]
methiothepin Rn Antagonist 7.5 – 9.4 pKi 4,6-7,28
pKi 7.5 – 9.4 [4,6-7,28]
chlorpromazine Rn Inverse agonist 8.4 pKi 37
pKi 8.4 [37]
zotepine Hs Inverse agonist 8.3 pKi 35
pKi 8.3 [35]
thioridazine Rn Inverse agonist 8.2 pKi 37
pKi 8.2 [37]
Ro 63-0563 Hs Antagonist 7.9 – 8.4 pKi 7,40
pKi 7.9 – 8.4 (Ki 1.26x10-8 – 3.98x10-9 M) [7,40]
olanzapine Rn Inverse agonist 7.6 – 8.6 pKi 22,37
pKi 7.6 – 8.6 [22,37]
dihydroergotamine Rn Antagonist 7.9 – 8.3 pKi 6,28
pKi 7.9 – 8.3 [6,28]
olanzapine Hs Inverse agonist 8.0 pKi 21,35
pKi 8.0 [21,35]
ICI 169369 Hs Antagonist 8.0 pKi 21
pKi 8.0 [21]
clozapine Hs Inverse agonist 7.8 – 8.1 pKi 5,7,21,35
pKi 7.8 – 8.1 [5,7,21,35]
clozapine Rn Inverse agonist 7.5 – 8.4 pKi 4,6-7,22,27-28,37
pKi 7.5 – 8.4 [4,6-7,22,27-28,37]
Ro 63-0563 Rn Antagonist 7.8 – 8.0 pKi 7,40
pKi 7.8 – 8.0 [7,40]
amoxapine Rn Antagonist 7.5 – 8.2 pKi 28,37
pKi 7.5 – 8.2 [28,37]
fluphenazine Rn Inverse agonist 7.8 pKi 37
pKi 7.8 [37]
perphenazine Rn Inverse agonist 7.8 pKi 37
pKi 7.8 [37]
2-bromo-LSD Rn Antagonist 7.8 pKi 28
pKi 7.8 [28]
fluperlapine Rn Inverse agonist 7.8 pKi 37
pKi 7.8 [37]
chlorpromazine Hs Inverse agonist 7.7 – 7.8 pKi 21,35
pKi 7.7 – 7.8 [21,35]
MPDT Hs Antagonist 7.7 pKi 14
pKi 7.7 [14]
bufotenine Rn Antagonist 7.0 – 8.4 pKi 4
pKi 7.0 – 8.4 [4]
Ro 04-6790 Hs Antagonist 7.3 – 7.9 pKi 7,40
pKi 7.3 – 7.9 [7,40]
loxapine Hs Inverse agonist 7.4 – 7.6 pKi 21,35
pKi 7.4 – 7.6 [21,35]
loxapine Rn Inverse agonist 7.2 – 7.8 pKi 28,37
pKi 7.2 – 7.8 [28,37]
Ro 04-6790 Rn Antagonist 7.4 – 7.6 pKi 7,40
pKi 7.4 – 7.6 [7,40]
iloperidone Rn Antagonist 7.4 pKi 22
pKi 7.4 [22]
fluperlapine Hs Inverse agonist 7.3 – 7.5 pKi 21,35
pKi 7.3 – 7.5 [21,35]
fluphenazine Hs Inverse agonist 7.3 – 7.4 pKi 35
pKi 7.3 – 7.4 [35]
amoxapine Hs Antagonist 7.3 pKi 21
pKi 7.3 [21]
α-ergocryptine Rn Antagonist 7.3 pKi 6
pKi 7.3 [6]
iloperidone Hs Antagonist 7.2 pKi 19
pKi 7.2 [19]
pimozide Rn Antagonist 7.2 pKi 37
pKi 7.2 [37]
ritanserin Hs Antagonist 7.0 – 7.4 pKi 5,7,21
pKi 7.0 – 7.4 [5,7,21]
thioridazine Hs Inverse agonist 7.2 pKi 35
pKi 7.2 [35]
dihydroergocristine Rn Antagonist 7.2 pKi 6
pKi 7.2 [6]
ritanserin Rn Antagonist 6.5 – 7.8 pKi 4,6-7,28
pKi 6.5 – 7.8 [4,6-7,28]
mianserin Rn Antagonist 6.9 – 7.4 pKi 4,7,28
pKi 6.9 – 7.4 [4,7,28]
mianserin Hs Antagonist 6.9 – 7.3 pKi 5,7,21
pKi 6.9 – 7.3 [5,7,21]
tiospirone Rn Antagonist 7.1 pKi 37
pKi 7.1 [37]
perphenazine Hs Inverse agonist 7.1 pKi 35
pKi 7.1 [35]
metergoline Rn Antagonist 6.6 – 7.5 pKi 4,6-7,28
pKi 6.6 – 7.5 [4,6-7,28]
amitriptyline Hs Antagonist 6.9 – 7.2 pKi 5,7,21
pKi 6.9 – 7.2 [5,7,21]
metergoline Hs Antagonist 6.4 – 7.4 pKi 5,7,21
pKi 6.4 – 7.4 [5,7,21]
cyproheptadine Rn Antagonist 6.9 pKi 28
pKi 6.9 [28]
amitriptyline Rn Antagonist 6.5 – 7.2 pKi 4,7,28
pKi 6.5 – 7.2 [4,7,28]
aripiprazole Rn Antagonist 6.8 pKi 25
pKi 6.8 [25]
cyproheptadine Hs Antagonist 6.8 pKi 21
pKi 6.8 [21]
methysergide Hs Antagonist 6.5 – 6.8 pKi 5,7,21
pKi 6.5 – 6.8 [5,7,21]
methysergide Rn Antagonist 6.4 – 6.6 pKi 4,6-7,28
pKi 6.4 – 6.6 [4,6-7,28]
vortioxetine Hs Antagonist 6.5 pKi 1
pKi 6.5 (Ki 3.3x10-7 M) [1]
duloxetine Hs Antagonist 6.4 pKi 12
pKi 6.4 [12]
risperidone Rn Inverse agonist 6.0 – 6.4 pKi 22,37
pKi 6.0 – 6.4 [22,37]
tiospirone Hs Antagonist 6.0 pKi 21
pKi 6.0 [21]
spiperone Rn Antagonist 5.8 pKi 37
pKi 5.8 [37]
fluoxetine Rn Antagonist 5.8 pKi 28
pKi 5.8 [28]
sumatriptan Hs Antagonist 5.6 pKi 21
pKi 5.6 [21]
risperidone Hs Antagonist 5.6 pKi 21
pKi 5.6 [21]
mesulergine Hs Antagonist 5.4 – 5.7 pKi 5,7,21
pKi 5.4 – 5.7 [5,7,21]
mesulergine Rn Antagonist 5.1 – 5.8 pKi 4,7,28
pKi 5.1 – 5.8 [4,7,28]
sumatriptan Rn Antagonist 5.2 pKi 6
pKi 5.2 [6]
View species-specific antagonist tables
Antagonist Comments
5-HT6 receptor antagonists have been developed as potential add-on, cognition-enhancing clinical candidate for Alzheimer's disease. However, none of these have yet shown efficacy in Phase 3 trials: Pfizer's PF-05212377 failed Phase 2 in October 2015, and Lundbeck reported failure of all of its Phase 3 trials of idalopirdine (2016/17). Axovant Science still has RVT-101 (intepirdine) in Phase 3 trial, with reporting expected in the second half of 2017.
Primary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
References:  45
Secondary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
References:  45
Tissue Distribution
Superior cervical ganglia.
Species:  Rat
Technique:  RT-PCR.
References:  33
Thymus, peripheral blood lymphocytes, spleen, mitogen-activated spleen cells.
Species:  Rat
Technique:  RT-PCR.
References:  41
Brain: nucleus accumbens, olfactory tubercle, striatum, hippocampus, anterior corpus.
Species:  Rat
Technique:  in situ hybridisation.
References:  44
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 intracellular Ca2+ levels in HEK 293 cells transfected with the human 5-HT6 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Increase in intracellular Ca2+ levels.
References:  45
Measurement of cAMP levels in HEK 293 cells transfected with the human 5-HT6 receptor.
Species: