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D2 receptor

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Target id: 215

Nomenclature: D2 receptor

Family: Dopamine receptors

Contents:

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 8,44
Mouse 7 444 9 26.72 cM Drd2 dopamine receptor D2 86
Rat 7 444 8q23 Drd2 dopamine receptor D2 8,23
Gene and Protein Information Comments
The human D2 receptor exists as two alternatively spliced isoforms [43]. 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 | D2R | dopamine D2 receptor | dopamine receptor 2 | 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 P14416 (Hs), P61168 (Mm), P61169 (Rn)
ChEMBL Target CHEMBL217 (Hs), CHEMBL3427 (Mm), CHEMBL339 (Rn)
DrugBank Target P14416 (Hs)
Ensembl Gene ENSG00000149295 (Hs), ENSMUSG00000032259 (Mm), ENSRNOG00000008428 (Rn)
Entrez Gene 1813 (Hs), 13489 (Mm), 24318 (Rn)
Human Protein Atlas ENSG00000149295 (Hs)
KEGG Gene hsa:1813 (Hs), mmu:13489 (Mm), rno:24318 (Rn)
OMIM 126450 (Hs)
Orphanet ORPHA121177 (Hs)
Pharos P14416 (Hs)
RefSeq Nucleotide NM_000795 (Hs), NM_010077 (Mm), NM_012547 (Rn)
RefSeq Protein NP_000786 (Hs), NP_034207 (Mm), NP_036679 (Rn)
UniProtKB P14416 (Hs), P61168 (Mm), P61169 (Rn)
Wikipedia DRD2 (Hs)
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:  130
Natural/Endogenous Ligands Click here for help
dopamine

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Agonists
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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 Hs Agonist 10.2 pKi 36
⤷ pKi 10.2 (Ki 6x10-11 M) [36]
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 102
⤷ pKi 9.7 [102]
brexpiprazole Small molecule or natural product Approved drug Hs Partial agonist 9.5 pKi 74
⤷ pKi 9.5 (Ki 3x10-10 M) [74]
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 84
⤷ pKi 9.2 – 9.5 [84]
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 136
⤷ pKi 9.1 (Ki 8x10-10 M) [136]
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 84
⤷ pKi 9.0 – 9.2 [84]
terguride Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 9.1 pKi 84
⤷ pKi 9.1 [84]
roxindole Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 8.6 pKi 84
⤷ pKi 8.6 [84]
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 39
⤷ pKi 8.2 (Ki 5.9x10-9 M) [39]
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 40,100
⤷ pKi 7.5 – 8.9 [40,100]
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 48
⤷ pKi 8.1 (Ki 7.2x10-9 M) [48]
LP-44 Small molecule or natural product Click here for species-specific activity table Hs Agonist 8.1 pKi 69
⤷ pKi 8.1 (Ki 7.3x10-9 M) [69]
sumanirole Small molecule or natural product Hs Full agonist 8.1 pKi 81
⤷ pKi 8.1 (Ki 9x10-9 M) [81]
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 40,84,100
⤷ pKi 7.3 – 8.3 [40,84,100]
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 118
⤷ pKi 7.6 [118]
pergolide Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 7.5 – 7.6 pKi 84
⤷ pKi 7.5 – 7.6 [84]
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 118
⤷ pKi 7.3 [118]
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 119
⤷ pKi 6.9 (Ki 1.18x10-7 M) [119]
piribedil Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 6.8 – 6.9 pKi 84
⤷ pKi 6.8 – 6.9 [84]
LP-211 Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.8 pKi 70
⤷ pKi 6.8 (Ki 1.42x10-7 M) [70]
LP-12 Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.7 pKi 69
⤷ pKi 6.7 (Ki 2.24x10-7 M) [69]
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 24,40,84,100,116
⤷ pKi 5.7 – 7.5 [24,40,84,100,116]
7-OH-DPAT Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.6 – 7.6 pKi 24,40,73
⤷ pKi 5.6 – 7.6 [24,40,73]
HS665 Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.3 pKi 119
⤷ pKi 6.3 (Ki 4.5x10-7 M) [119]
quinpirole Small molecule or natural product Click here for species-specific activity table Hs Full agonist 4.9 – 7.7 pKi 24,83,90,116,118,127
⤷ pKi 4.9 – 7.7 [24,83,90,116,118,127]
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 83,100
⤷ pKi 5.1 – 7.4 [83,100]
7-OH-DPAT Small molecule or natural product Rn Full agonist 6.2 pKi 32
⤷ pKi 6.2 [32]
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 24,40,100
⤷ pKi 4.7 – 7.2 [24,40,100]
PD 128907 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.4 – 6.4 pKi 92,100
⤷ pKi 5.4 – 6.4 [92,100]
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 102,118
⤷ pKi 5.3 – 6.4 [102,118]
7-trans-OH-PIPAT Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.6 pKi 32
⤷ pKi 5.6 [32]
quinelorane Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.5 – 5.7 pKi 85,116
⤷ pKi 5.5 – 5.7 [85,116]
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 45
⤷ pKi 5.4 (Ki 3.964x10-6 M) [45]
quinpirole Small molecule or natural product Click here for species-specific activity table Rn Full agonist 5.2 pKi 118
⤷ pKi 5.2 [118]
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 50
⤷ pIC50 6.2 (IC50 6.66x10-7 M) [50]
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 [45] 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 [68].
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 [113].
Antagonists
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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 75
⤷ pKd 10.9 [75]
[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 23,51,139
⤷ pKd 10.2 (Kd 5.7x10-11 M) [23,51,139]
[3H]raclopride Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Antagonist 8.9 pKd 65
⤷ pKd 8.9 (Kd 1.2x10-9 M) [65]
[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 102
⤷ pKi 10.7 [102]
benperidol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 10.6 pKi 109
⤷ pKi 10.6 (Ki 2.7x10-11 M) [109]
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 88
⤷ pKi 9.9 (Ki 1.4x10-10 M) [88]
pipotiazine Small molecule or natural product Approved drug Primary target of this compound Hs Antagonist 9.7 pKi 117
⤷ pKi 9.7 (Ki 2x10-10 M) [117]
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 10
⤷ pKi 9.4 (Ki 4.4x10-10 M) [10]
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 62,106
⤷ pKi 8.9 – 9.6 (Ki 1.4x10-9 – 2.6x10-10 M) [62,106]
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 107
⤷ pKi 9.2 (Ki 6x10-10 M) [107]
eticlopride Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 9.2 pKi 73,123
⤷ pKi 9.2 [73,123]
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 62,108
⤷ pKi 8.9 – 9.0 (Ki 1.3x10-9 – 9.6x10-10 M) [62,108]
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 112
⤷ pKi 8.9 (Ki 1.2x10-9 M) [112]
terguride Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.9 pKi 84
⤷ pKi 8.9 [84]
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 73,85,118,123
⤷ pKi 8.4 – 9.4 [73,85,118,123]
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 99
⤷ pKi 8.8 (Ki 1.44x10-9 M) [99]
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 40
⤷ pKi 8.8 (Ki 1.5x10-9 M) [40]
nafadotride Small molecule or natural product Click here for species-specific activity table Rn Antagonist 8.8 pKi 102
⤷ pKi 8.8 [102]
lurasidone Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 8.8 pKi 54
⤷ pKi 8.8 (Ki 1.68x10-9 M) [54]
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 10
⤷ pKi 8.7 (Ki 2.1x10-9 M) [10]
mesoridazine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.7 pKi 31
⤷ pKi 8.7 (Ki 2.2x10-9 M) [31]
roxindole Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.6 pKi 84
⤷ pKi 8.6 [84]
ziprasidone Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.6 pKi 10
⤷ pKi 8.6 (Ki 2.8x10-9 M) [10]
chlorprothixene Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.5 pKi 128
⤷ pKi 8.5 (Ki 2.96x10-9 M) [128]
nafadotride Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.5 pKi 101
⤷ pKi 8.5 [101]
raclopride Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.7 – 9.3 pKi 102,118
⤷ pKi 7.7 – 9.3 [102,118]
domperidone Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 8.5 pKi 118
⤷ pKi 8.5 [118]
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 61-62,106
⤷ pKi 8.0 – 8.9 (Ki 9.1x10-9 – 1.2x10-9 M) [61-62,106]
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 12
⤷ pKi 8.4 (Ki 3.61x10-9 M) [12]
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 118
⤷ pKi 8.3 [118]
(+)-sulpiride Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.2 pKi 40
⤷ pKi 8.2 (Ki 6x10-9 M) [40]
L-741,626 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.9 – 8.5 pKi 46,64
⤷ pKi 7.9 – 8.5 [46,64]
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 40,116
⤷ pKi 7.9 – 8.4 (Ki 1.26x10-8 – 3.98x10-9 M) [40,116]
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 62,108
⤷ pKi 7.9 – 8.3 (Ki 1.2x10-8 – 5x10-9 M) [62,108]
(+)-butaclamol Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.5 – 8.7 pKi 24,40,73,123
⤷ pKi 7.5 – 8.7 [24,40,73,123]
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 40,73,83,116,124
⤷ pKi 7.4 – 8.8 [40,73,83,116,124]
raclopride Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.0 pKi 85
⤷ pKi 8.0 (Ki 1x10-8 M) [85]
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 105
⤷ pKi 8.0 (Ki 1.1x10-8 M) [105]
(-)-stepholidine Small molecule or natural product Hs Antagonist 7.9 pKi 82
⤷ pKi 7.9 (Ki 1.16x10-8 M) [82]
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 40,116
⤷ pKi 7.0 – 8.8 [40,116]
amisulpride Small molecule or natural product Approved drug Primary target of this compound Hs Antagonist 7.8 – 8.0 pKi 77,116,118
⤷ pKi 7.9 – 8.0 [77,116]
pKi 7.8 [118]
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 118
⤷ pKi 7.6 [118]
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 24
⤷ pKi 7.2 – 7.9 (Ki 6x10-8 – 1.2x10-8 M) [24]
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 79
⤷ pKi 7.5 (Ki 2.88x10-8 M) [79]
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 118
⤷ pKi 7.5 [118]
lumateperone Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.5 pKi 71,115
⤷ pKi 7.5 (Ki 3.2x10-8 M) [71,115]
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 40,116
⤷ pKi 7.0 – 7.6 [40,116]
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 10
⤷ pKi 7.2 (Ki 6.9x10-8 M) [10]
(-)-sulpiride Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 6.3 – 8.0 pKi 40,116,123
⤷ pKi 6.3 – 8.0 (Ki 5.2x10-7 – 1x10-8 M) [40,116,123]
R-VK4-40 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.1 pKi 56
⤷ pKi 7.1 (Ki 7.58x10-8 M) [56]
(+)-sulpiride Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.0 pKi 118
⤷ pKi 7.0 [118]
ML321 Small molecule or natural product Primary target of this compound Hs Antagonist 7.0 pKi 133-134
⤷ pKi 7.0 (Ki 1x10-7 M) [133-134]
trans-flupenthixol Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.9 pKi 40
⤷ pKi 6.9 (Ki 1.2x10-7 M) [40]
EGIS-11150 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]
(+)-UH232 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.4 – 7.1 pKi 40,118
⤷ pKi 6.4 – 7.1 [40,118]
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 25
⤷ pKi 6.5 (Ki 3x10-7 M) [25]
(+)-UH232 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 6.4 pKi 118
⤷ pKi 6.4 [118]
clozapine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 5.8 – 6.9 pKi 40,73,112,116,123
⤷ pKi 5.8 – 6.9 [40,73,112,116,123]
clozapine Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 6.2 pKi 118
⤷ pKi 6.2 [118]
(+)-S-14297 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.5 pKi 85
⤷ pKi 5.5 [85]
(+)-SCH-23390 Small molecule or natural product Hs Antagonist 5.3 pKi 40
⤷ pKi 5.3 [40]
iloperidone Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 7.0 pIC50 121
⤷ pIC50 7.0 (IC50 1.1x10-7 M) [121]
Description: Measuring displacement of [3H]spiperone from rat striatum.
metopimazine Small molecule or natural product Approved drug N/A Antagonist - -
⤷
alizapride Small molecule or natural product Approved drug N/A Antagonist - -
⤷
View species-specific antagonist tables
Antagonist Comments
Terguride/roxindole have been reported to act as partial agonists at the D2S receptor and as antagonists at the D2L receptor.
Perphenazine is an antagonist at both the D2S and D2L receptors [122].
The approved drug mesoridazine, although consisting of 4 stereoisomers, appears to be selective for the D2 receptor [31], especially when examining the data for the two highest affinity isomers, compounds 2 and 5. Across the 3 dopamine receptors, compounds 2 and 5 have the same order of potency (D2>D3>D1). The data shown in the table above is for compound 2. Mesoridazine is also a selective antagonist of the serotonin 5-HT2A receptor.
Zotepine has a Ki of 5.4nM for the D2S receptor isoform [105].
The β-arrestin biased ligands UNC9975, UNC0006 and UNC9994, do not activate D2 receptor-mediated Gi-regulated inhibition of cAMP production, but rather are functionally-selective antagonists of the interaction between D2 receptor and β-arrestin-2 [3].
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
SB269652 Small molecule or natural product