Top ▲

D2 receptor

Click here for help

Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 215

Nomenclature: D2 receptor

Family: Dopamine receptors

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 443 11q23.2 DRD2 dopamine receptor D2 9,45
Mouse 7 444 9 26.72 cM Drd2 dopamine receptor D2 88
Rat 7 444 8q23 Drd2 dopamine receptor D2 9,24
Gene and Protein Information Comments
The human D2 receptor exists as two alternatively spliced isoforms [44]. The 443 amino acid receptor is the long form (D2L). The short form (D2S) is 414 amino acids long.
Previous and Unofficial Names Click here for help
D2A and D2B | dopamine D2 receptor | dopamine receptor 2 | D2R | D2 receptor | D2(415) and D2(444)
Database Links Click here for help
Specialist databases
GPCRdb drd2_human (Hs), drd2_mouse (Mm), drd2_rat (Rn)
Other databases
Alphafold
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the D2 dopamine receptor bound to the atypical antipsychotic drug risperidone
PDB Id:  6CM4
Ligand:  risperidone
Resolution:  2.9Å
Species:  Human
References:  132
Natural/Endogenous Ligands Click here for help
dopamine

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
rotigotine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 10.2 pKi 37
pKi 10.2 (Ki 6x10-11 M) [37]
aripiprazole Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Partial agonist 9.7 pKi 104
pKi 9.7 [104]
brexpiprazole Small molecule or natural product Approved drug Hs Partial agonist 9.5 pKi 76
pKi 9.5 (Ki 3x10-10 M) [76]
lisuride Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 9.2 – 9.5 pKi 86
pKi 9.2 – 9.5 [86]
aripiprazole Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 9.1 pKi 138
pKi 9.1 (Ki 8x10-10 M) [138]
cabergoline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Partial agonist 9.0 – 9.2 pKi 86
pKi 9.0 – 9.2 [86]
terguride Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 9.1 pKi 86
pKi 9.1 [86]
roxindole Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 8.6 pKi 86
pKi 8.6 [86]
UNC9975 Small molecule or natural product Hs Biased agonist 8.6 pKi 3
pKi 8.6 (Ki 2.6x10-9 M) [3]
Description: β-arrestin 2 biased agonist.
UNC0006 Small molecule or natural product Hs Biased agonist 8.3 pKi 3
pKi 8.3 (Ki 5x10-9 M) [3]
Description: β-arrestin 2 biased agonist.
cariprazine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 8.2 pKi 1
pKi 8.2 (Ki 5.7x10-9 M) [1]
Description: Binding affinity to human dopamine D2L receptor
MLS1547 Small molecule or natural product Hs Biased agonist 8.2 pKi 40
pKi 8.2 (Ki 5.9x10-9 M) [40]
Description: Biased agonist for G-protein coupling to Gi.
(-)-N-porphynorapomorphine Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.5 – 8.9 pKi 41,102
pKi 7.5 – 8.9 [41,102]
ropinirole Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Agonist 8.1 pKi 49
pKi 8.1 (Ki 7.2x10-9 M) [49]
LP-44 Small molecule or natural product Click here for species-specific activity table Hs Agonist 8.1 pKi 71
pKi 8.1 (Ki 7.3x10-9 M) [71]
sumanirole Small molecule or natural product Hs Full agonist 8.1 pKi 83
pKi 8.1 (Ki 9x10-9 M) [83]
bromocriptine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 7.3 – 8.3 pKi 41,86,102
pKi 7.3 – 8.3 [41,86,102]
apomorphine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Partial agonist 7.6 pKi 120
pKi 7.6 [120]
pergolide Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 7.5 – 7.6 pKi 86
pKi 7.5 – 7.6 [86]
bromocriptine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Partial agonist 7.3 pKi 120
pKi 7.3 [120]
UNC9994 Small molecule or natural product Hs Biased agonist 7.1 pKi 3
pKi 7.1 (Ki 7.9x10-8 M) [3]
Description: β-arrestin 2 biased agonist.
compound 3 [PMID: 23134120] Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.9 pKi 121
pKi 6.9 (Ki 1.18x10-7 M) [121]
piribedil Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 6.8 – 6.9 pKi 86
pKi 6.8 – 6.9 [86]
LP-211 Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.8 pKi 72
pKi 6.8 (Ki 1.42x10-7 M) [72]
LP-12 Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.7 pKi 71
pKi 6.7 (Ki 2.24x10-7 M) [71]
apomorphine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 5.7 – 7.5 pKi 25,41,86,102,118
pKi 5.7 – 7.5 [25,41,86,102,118]
7-OH-DPAT Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.6 – 7.6 pKi 25,41,75
pKi 5.6 – 7.6 [25,41,75]
HS665 Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.3 pKi 121
pKi 6.3 (Ki 4.5x10-7 M) [121]
quinpirole Small molecule or natural product Click here for species-specific activity table Hs Full agonist 4.9 – 7.7 pKi 25,85,92,118,120,129
pKi 4.9 – 7.7 [25,85,92,118,120,129]
pramipexole Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 5.1 – 7.4 pKi 85,102
pKi 5.1 – 7.4 [85,102]
7-OH-DPAT Small molecule or natural product Rn Full agonist 6.2 pKi 33
pKi 6.2 [33]
dopamine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 4.7 – 7.2 pKi 25,41,102
pKi 4.7 – 7.2 [25,41,102]
PD 128907 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.4 – 6.4 pKi 94,102
pKi 5.4 – 6.4 [94,102]
dopamine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Rn Full agonist 5.3 – 6.4 pKi 104,120
pKi 5.3 – 6.4 [104,120]
7-trans-OH-PIPAT Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.6 pKi 33
pKi 5.6 [33]
quinelorane Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.5 – 5.7 pKi 87,118
pKi 5.5 – 5.7 [87,118]
benzquinamide Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Agonist 5.4 pKi 46
pKi 5.4 (Ki 3.964x10-6 M) [46]
quinpirole Small molecule or natural product Click here for species-specific activity table Rn Full agonist 5.2 pKi 120
pKi 5.2 [120]
UNC9975 Small molecule or natural product Hs Biased agonist 9.0 pEC50 3
pEC50 9.0 (EC50 1.1x10-9 M) [3]
Description: This compound shows biased agonism towards D2-mediated β-arrestin-2 translocation measured using the Tango assay.
UNC0006 Small molecule or natural product Hs Biased agonist 8.9 pEC50 3
pEC50 8.9 (EC50 1.2x10-9 M) [3]
Description: Biased agonist of D2-mediated β-arrestin-2 translocation measured using the Tango assay.
UNC9994 Small molecule or natural product Hs Biased agonist 8.2 pEC50 3
pEC50 8.2 (EC50 6.1x10-9 M) [3]
Description: This compound shows biased agonism towards D2-mediated β-arrestin-2 translocation measured using the Tango assay.
aripiprazole Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 7.4 pEC50 3
pEC50 7.4 (EC50 3.8x10-8 M) [3]
Description: Measuring cAMP production via the Gi-coupled signaling pathway
vilazodone Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 6.2 pIC50 51
pIC50 6.2 (IC50 6.66x10-7 M) [51]
View species-specific agonist tables
Agonist Comments
Terguride and roxindole have been reported to be partial agonists at the D2S receptor and antagonists at the D2L receptor.
Although benzquinamide has higher affinity for α-adrenoceptors, it is suggested in [46] that it is more likely that drug-induced modulation of D2 receptor activity is responsible for the drug's antiemetic action.
Allosteric modulation of the D2 receptor by SB269652 only occurs when D2 receptor dimers form, with the ligand assuming a 'bitopic' pose and interacting with different sites on each of the two protomers in the dimer [70].
UNC0006, UNC9994 and UNC9975 are partial biased agonists of β-arrestin 2 recruitment at the D2 receptor as measured using three different assays (β-arrestin-2 translocation Tango assay, DiscoveRx assay and BRET-based β-arrestin-2 recruitment assay) [3]. Tango assay pEC50 values and binding Kis are provided in the table above.
G protein-biased, cariprazine-based partial agonists are reported in [115].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]nemonapride Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Antagonist 10.9 pKd 77
pKd 10.9 [77]
[3H]spiperone Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Ligand has a PDB structure Rn Antagonist 10.2 pKd 24,52,141
pKd 10.2 (Kd 5.7x10-11 M) [24,52,141]
[3H]raclopride Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Antagonist 8.9 pKd 67
pKd 8.9 (Kd 1.2x10-9 M) [67]
[3H]N-methylspiperone Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Rn Antagonist 10.7 pKi 104
pKi 10.7 [104]
benperidol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 10.6 pKi 111
pKi 10.6 (Ki 2.7x10-11 M) [111]
blonanserin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 9.9 pKi 90
pKi 9.9 (Ki 1.4x10-10 M) [90]
pipotiazine Small molecule or natural product Approved drug Primary target of this compound Hs Antagonist 9.7 pKi 119
pKi 9.7 (Ki 2x10-10 M) [119]
risperidone Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 9.4 pKi 11
pKi 9.4 (Ki 4.4x10-10 M) [11]
perphenazine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.9 – 9.6 pKi 64,108
pKi 8.9 – 9.6 (Ki 1.4x10-9 – 2.6x10-10 M) [64,108]
perospirone Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 9.2 pKi 109
pKi 9.2 (Ki 6x10-10 M) [109]
eticlopride Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 9.2 pKi 75,125
pKi 9.2 [75,125]
trifluoperazine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.9 – 9.0 pKi 64,110
pKi 8.9 – 9.0 (Ki 1.3x10-9 – 9.6x10-10 M) [64,110]
asenapine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.9 pKi 114
pKi 8.9 (Ki 1.2x10-9 M) [114]
terguride Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.9 pKi 86
pKi 8.9 [86]
spiperone Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 8.4 – 9.4 pKi 75,87,120,125
pKi 8.4 – 9.4 [75,87,120,125]
fluphenazine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.8 pKi 101
pKi 8.8 (Ki 1.44x10-9 M) [101]
flupentixol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.8 pKi 41
pKi 8.8 (Ki 1.5x10-9 M) [41]
nafadotride Small molecule or natural product Click here for species-specific activity table Rn Antagonist 8.8 pKi 104
pKi 8.8 [104]
lurasidone Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 8.8 pKi 55
pKi 8.8 (Ki 1.68x10-9 M) [55]
olanzapine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.7 pKi 11
pKi 8.7 (Ki 2.1x10-9 M) [11]
mesoridazine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.7 pKi 32
pKi 8.7 (Ki 2.2x10-9 M) [32]
roxindole Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.6 pKi 86
pKi 8.6 [86]
ziprasidone Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.6 pKi 11
pKi 8.6 (Ki 2.8x10-9 M) [11]
chlorprothixene Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.5 pKi 130
pKi 8.5 (Ki 2.96x10-9 M) [130]
nafadotride Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.5 pKi 103
pKi 8.5 [103]
raclopride Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.7 – 9.3 pKi 104,120
pKi 7.7 – 9.3 [104,120]
domperidone Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 8.5 pKi 120
pKi 8.5 [120]
sertindole Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.0 – 8.9 pKi 63-64,108
pKi 8.0 – 8.9 (Ki 9.1x10-9 – 1.2x10-9 M) [63-64,108]
prochlorperazine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.4 pKi 13
pKi 8.4 (Ki 3.61x10-9 M) [13]
haloperidol Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 8.3 pKi 120
pKi 8.3 [120]
(+)-sulpiride Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.2 pKi 41
pKi 8.2 (Ki 6x10-9 M) [41]
L-741,626 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.9 – 8.5 pKi 47,66
pKi 7.9 – 8.5 [47,66]
domperidone Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.9 – 8.4 pKi 41,118
pKi 7.9 – 8.4 (Ki 1.26x10-8 – 3.98x10-9 M) [41,118]
loxapine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.9 – 8.3 pKi 64,110
pKi 7.9 – 8.3 (Ki 1.2x10-8 – 5x10-9 M) [64,110]
(+)-butaclamol Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.5 – 8.7 pKi 25,41,75,125
pKi 7.5 – 8.7 [25,41,75,125]
haloperidol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.4 – 8.8 pKi 41,75,85,118,126
pKi 7.4 – 8.8 [41,75,85,118,126]
raclopride Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.0 pKi 87
pKi 8.0 (Ki 1x10-8 M) [87]
zotepine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.0 pKi 107
pKi 8.0 (Ki 1.1x10-8 M) [107]
(-)-stepholidine Small molecule or natural product Hs Antagonist 7.9 pKi 84
pKi 7.9 (Ki 1.16x10-8 M) [84]
pimozide Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.0 – 8.8 pKi 41,118
pKi 7.0 – 8.8 [41,118]
amisulpride Small molecule or natural product Approved drug Primary target of this compound Hs Antagonist 7.8 – 8.0 pKi 79,118,120
pKi 7.9 – 8.0 [79,118]
pKi 7.8 [120]
cinnarizine Small molecule or natural product Approved drug Ligand has a PDB structure Rn Antagonist 7.9 pKi 58
pKi 7.9 (Ki 1.32x10-8 M) [58]
flunarizine Small molecule or natural product Approved drug Rn Antagonist 6.9 – 8.4 pKi 4,58
pKi 6.9 – 8.4 (Ki 1.12x10-7 – 3.96x10-9 M) [4,58]
pimozide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 7.6 pKi 120
pKi 7.6 [120]
sulpiride Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.2 – 7.9 pKi 25
pKi 7.2 – 7.9 (Ki 6x10-8 – 1.2x10-8 M) [25]
metoclopramide Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Mm Antagonist 7.5 pKi 81
pKi 7.5 (Ki 2.88x10-8 M) [81]
chlorpromazine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 7.5 pKi 120
pKi 7.5 [120]
lumateperone Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.5 pKi 73,117
pKi 7.5 (Ki 3.2x10-8 M) [73,117]
chlorpromazine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.0 – 7.6 pKi 41,118
pKi 7.0 – 7.6 [41,118]
quetiapine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.2 pKi 11
pKi 7.2 (Ki 6.9x10-8 M) [11]
(-)-sulpiride Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.3 – 8.0 pKi 41,118,125
pKi 6.3 – 8.0 (Ki 5.2x10-7 – 1x10-8 M) [41,118,125]
R-VK4-40 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.1 pKi 57
pKi 7.1 (Ki 7.58x10-8 M) [57]
(+)-sulpiride Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.0 pKi 120
pKi 7.0 [120]
ML321 Small molecule or natural product Primary target of this compound Hs Antagonist 7.0 pKi 135-136
pKi 7.0 (Ki 1x10-7 M) [135-136]
trans-flupenthixol Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.9 pKi 41
pKi 6.9 (Ki 1.2x10-7 M) [41]
EGIS-11150 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.9 pKi 42
pKi 6.9 (Ki 1.2x10-7 M) [42]
(+)-UH232 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.4 – 7.1 pKi 41,120
pKi 6.4 – 7.1 [41,120]
promazine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.5 pKi 26
pKi 6.5 (Ki 3x10-7 M) [26]
(+)-UH232 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 6.4 pKi 120
pKi 6.4 [120]
clozapine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 5.8 – 6.9 pKi 41,75,114,118,125
pKi 5.8 – 6.9 [41,75,114,118,125]
clozapine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 6.2 pKi 120
pKi 6.2 [120]
(+)-S-14297 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.5 pKi 87
pKi 5.5 [87]
(+)-SCH-23390 Small molecule or natural product Hs Antagonist 5.3 pKi 41
pKi 5.3 [41]
iloperidone Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 7.0 pIC50 123
pIC50 7.0 (IC50 1.1x10-7 M) [123]
Description: Measuring displacement of [3H]spiperone from rat striatum.
metopimazine Small molecule or natural product