DRD2

Summary

DRD2 (dopamine receptor D2, HGNC:3023) is a protein-coding gene on chromosome 11q23.2, encoding D(2) dopamine receptor (P14416). Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.

This gene encodes the D2 subtype of the dopamine receptor. This G-protein coupled receptor inhibits adenylyl cyclase activity. A missense mutation in this gene causes myoclonus dystonia; other mutations have been associated with schizophrenia. Alternative splicing of this gene results in two transcript variants encoding different isoforms. A third variant has been described, but it has not been determined whether this form is normal or due to aberrant splicing.

Source: NCBI Gene 1813 — RefSeq curated summary.

At a glance

• Gene–disease (curated): combined dystonia (Moderate, GenCC)
• GWAS associations: 49
• Clinical variants (ClinVar): 175 total
• Phenotypes (HPO): 11
• Druggable target: yes — 298 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000795

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3023
Approved symbol	DRD2
Name	dopamine receptor D2
Location	11q23.2
Locus type	gene with protein product
Status	Approved
Aliases	D2R
Ensembl gene	ENSG00000149295
Ensembl biotype	protein_coding
OMIM	126450
Entrez	1813

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000346454, ENST00000362072, ENST00000535984, ENST00000538967, ENST00000539420, ENST00000540600, ENST00000542616, ENST00000542968, ENST00000543292, ENST00000544518, ENST00000907485, ENST00000907486, ENST00000907487

RefSeq mRNA: 2 — MANE Select: NM_000795 NM_000795, NM_016574

CCDS: CCDS8361, CCDS8362

Canonical transcript exons

ENST00000362072 — 8 exons

Exon	Start	End
ENSE00001247012	113412556	113412883
ENSE00002282098	113475076	113475398
ENSE00003475700	113414375	113414461
ENSE00003518665	113415421	113415611
ENSE00003641994	113418027	113418136
ENSE00003665261	113424367	113424682
ENSE00003790357	113416863	113416999
ENSE00003850884	113409605	113410920

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 92.52.

FANTOM5 (CAGE): breadth broad, TPM avg 2.3403 / max 243.0619, expressed in 265 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122347	0.8608	146
122348	0.4939	110
122345	0.4323	129
122346	0.2448	84
122338	0.2242	16
122337	0.0333	11
122341	0.0168	8
122344	0.0116	6
122342	0.0074	6
122339	0.0057	3

Top tissues by expression

277 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
putamen	UBERON:0001874	92.52	gold quality
nucleus accumbens	UBERON:0001882	92.18	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.99	gold quality
pituitary gland	UBERON:0000007	91.54	gold quality
caudate nucleus	UBERON:0001873	90.67	gold quality
adenohypophysis	UBERON:0002196	90.28	gold quality
triceps brachii	UBERON:0001509	83.99	silver quality
pancreatic ductal cell	CL:0002079	83.38	silver quality
substantia nigra pars compacta	UBERON:0001965	83.20	gold quality
substantia nigra pars reticulata	UBERON:0001966	83.14	gold quality
vena cava	UBERON:0004087	82.52	gold quality
pons	UBERON:0000988	81.72	silver quality
ventral tegmental area	UBERON:0002691	80.33	silver quality
pharyngeal mucosa	UBERON:0000355	79.70	gold quality
cardia of stomach	UBERON:0001162	79.14	gold quality
buccal mucosa cell	CL:0002336	79.13	gold quality
epithelial cell of pancreas	CL:0000083	79.07	gold quality
midbrain	UBERON:0001891	78.89	gold quality
substantia nigra	UBERON:0002038	78.83	gold quality
tendon of biceps brachii	UBERON:0008188	78.47	gold quality
body of tongue	UBERON:0011876	78.46	gold quality
gluteal muscle	UBERON:0002000	78.36	gold quality
pylorus	UBERON:0001166	78.26	gold quality
inferior vagus X ganglion	UBERON:0005363	78.00	gold quality
superior surface of tongue	UBERON:0007371	77.93	gold quality
lateral globus pallidus	UBERON:0002476	77.92	silver quality
pericardium	UBERON:0002407	77.88	gold quality
nipple	UBERON:0002030	77.71	gold quality
saphenous vein	UBERON:0007318	77.71	gold quality
minor salivary gland	UBERON:0001830	77.67	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.03

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ATF4, EGR1, FOSB, KAT7, KLF11, KLF16, NFKB1, NFKB, REL, RELA, SP1, SP3, TAF1, ZNF804A

miRNA regulators (miRDB)

45 targeting DRD2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4480	99.42	66.02	735
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-5011-3P	98.63	64.81	638
HSA-MIR-4490	98.51	68.47	943
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-326	98.25	66.44	1565

Literature-anchored findings (GeneRIF, showing 40)

• An association has been found between DRD2 exon 8 homozygous A/A genotype and increased dose of dopamine D2 antagonist tiapride for treatment of alcohol withdrawal symptomatology. (PMID:11692072)
• peripheral dopamine D1 and D2 receptors are present in the seminal vesicle tissue (PMID:11783439)
• results suggest that both the DRD2 promoter region and the DAT gene do not play a significant role in conferring vulnerability to alcoholism (Dopamine Transporter DAT) (PMID:11807408)
• nerve growth factor regulates dopamine D(2) receptor expression in prolactinoma cell lines via p75(NGFR)-mediated activation of nuclear factor-kappaB (PMID:11818506)
• Possibly related to attention deficit hyperactivity disorder, but no mutations have been found to be associated. (PMID:11840503)
• seletive intramembrane interactions with adenosine A2A receptors (PMID:11872740)
• no association of polymorphism and methamphetamine abuse in Chinese males (PMID:11901357)
• Patterns of cyclic AMP formation by coexpressed D1 and D2L dopamine receptors in HEK 293 cells. Patterns of cyclic AMP formation by coexpressed D1 and D2L dopamine receptors in HEK 293 cells. (PMID:11918350)
• dopamine depletion results in increased neostriatal binding (PMID:11920160)
• possible influence of monoamine oxydase A (MAO-A), catechol-O-methyltransferase (COMT), serotonin receptor 2A (5-HT2A), dopamine receptor D2 (DRD2), and dopamine receptor D4 (DRD4) gene variants on timing of recurrence in mood disorders (PMID:11992560)
• Lack of association between -141C Ins/Del promoter polymorphism of DRD2 gene and schizophrenia. (PMID:12149917)
• Among the aged with cognitive impairments, the homozygous status for the A2 allele of the DRD2 Taq I polymorphism is associated with diminished cognitive performance and increased atrophy in the striatum. (PMID:12151753)
• protein 4.1N/dopamine receptor interaction is required for localization or stability of dopamine receptors at the neuronal plasma membrane. (PMID:12181426)
• genetic variations in the DRD2 gene were no major predictors of the individually variable adverse effects from antipsychotic treatment in Caucasian schizophrenic patients. (PMID:12192613)
• Gender-specific molecular heterosis of dopamine D2 receptor gene (DRD2) for smoking in schizophrenia (PMID:12210271)
• This study suggests that these polymorphisms are not related to the development of tardive dystonia. (PMID:12210290)
• Based on DRD2 allelic association, the 35 PTSD patients with the A1(+) (A1A1, A1A2) allele consumed more than twice the daily amount of alcohol than the 56 patients with the A1(-) (A2A2) allele (P = 1.94 x 10(-3)). (PMID:12217937)
• a potential role for the dopamine-2 receptor in the genetic etiology of schizophrenia in a genetically homogeneous Portuguese population (PMID:12399954)
• the fourth transmembrane segment (TM4) forms a symmetrical dimer interface in the dopamine D2 receptor (PMID:12496294)
• Significant age-related decline was observed for dopamine receptor mRNAs in the hippocampus and entorhinal cortex (PMID:12509874)
• study suggests that only the TaqI A polymorphism is associated with neuroleptic malignant syndrome, but the -141 C Ins/Del and Ser(9)Gly polymorphisms are not (PMID:12555236)
• There is a lack of association in Japanese patients between neuroleptic malignant syndrome and the TaqI A polymorphism of this gene. (PMID:12605103)
• Results indicate that gender-specific molecular heterosis at Dopamine D2 Receptor (DRD2) gene for smoking is also applicable in healthy individuals. (PMID:12627467)
• higher efficiency activation of Go by the D(2S) receptor may be a function of higher affinity receptor/G protein interaction as well as a greater ability to activate the G protein. (PMID:12663049)
• extrastriatal D(2/3) density in drug-naive schizophrenic patients (PMID:12740603)
• a possible linkage with schizophrenia for the Taq1A marker but not for the Taq1B marker of DRD2 gene. (PMID:12762588)
• Among type 1 alcoholics dopamine transporters are lower in nucleus accumbens and dopamine D(2), but not D(1) or D(3) receptors in nucleus accumbens and amygdala. Lower dopamine receptor density is specific for D(2) receptor and for type 1 alcoholism. (PMID:12781734)
• Reward-related impulsiveness may constitute a risk factor for alcohol dependence, and this core temperament could be partly mediated by the DRD2 gene. (PMID:12782972)
• The human D2 dopamine receptor synergizes with the A2A adenosine receptor to stimulate adenylyl cyclase in PC12 cells. (PMID:12784121)
• dopamine receptor D2 oligomerizes with adenosine A(2A) receptor in living cells (PMID:12804599)
• There is no evidence of molecular heterosis at DRD2 for smoking in schizophrenia. (PMID:12815737)
• Preliminary results of a single photon emission computed tomography (SPECT) study point to striatal D2R density as a predictor of premorbid and clinical features associated with poor prognosis in neuroleptic-naive patients. (PMID:12921907)
• In the most probable of two possible modes of interaction between D2R and A2AR, helix 5 and/or helix 6 and the N-terminal portion of I3 from D2R approached helix 4 and the C-terminal portion of the C-tail from the A2AR, respectively (PMID:12933819)
• the point mutation in position 311 has little impact on the downstream signalling of dopamine d2 receptors (PMID:12967602)
• These results support the hypothesis that specific dopamine agonists stabilize distinct conformations of the D2 receptor that differ in their coupling to G-proteins and to a cytoprotective c-Src/EGFR-mediated PI-3 kinase/Akt pathway. (PMID:12970364)
• In a family based approach 190 German family trios were analyzed for the -141C Ins/Del genotype. Our data do not support the hypothesis that the -141C Ins variant plays a major role in predisposition to schizophrenia (PMID:14509080)
• The findings suggest that the frequency of the -141C Ins/Del polymorphism is lower in Northern Europe compared to other Caucasian and Japanese populations. (PMID:14572625)
• increase in D2 receptor availability in the left putamen and the decrease in D1/D2 ratio imply that alterations in the striatal dopaminergic system as evaluated by PET may be involved in chronic orofacial pain conditions (PMID:14581109)
• region of the third cytoplasmic loop of Dopamine D2 receptor is crucial for determining G(i) protein coupling specificity. (PMID:14581469)
• extracellular loop E2 likely contributes to the binding site in the dopamine D2 receptor (PMID:14704269)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	drd2b	ENSDARG00000011091
danio_rerio	drd2a	ENSDARG00000056926
mus_musculus	Drd2	ENSMUSG00000032259
rattus_norvegicus	Drd2	ENSRNOG00000008428
caenorhabditis_elegans	ser-5	WBGENE00008890

Paralogs (18): ADRB1 (ENSG00000043591), ADRA1A (ENSG00000120907), ADRA2A (ENSG00000150594), GPR101 (ENSG00000165370), ADRB2 (ENSG00000169252), ADRA1B (ENSG00000170214), ADRA1D (ENSG00000171873), OR5T3 (ENSG00000172489), OR56A1 (ENSG00000180934), OR5T1 (ENSG00000181698), OR5T2 (ENSG00000181718), OR56A4 (ENSG00000183389), ADRA2C (ENSG00000184160), OR56A3 (ENSG00000184478), OR13F1 (ENSG00000186881), OR56A5 (ENSG00000188691), ADRB3 (ENSG00000188778), ADRA2B (ENSG00000274286)

Protein

Protein identifiers

D(2) dopamine receptor — P14416 (reviewed: P14416)

Alternative names: Dopamine D2 receptor

All UniProt accessions (4): P14416, A0A1Y8EK52, F8VUV1, Q6LDH7

UniProt curated annotations — full annotation on UniProt →

Function. Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Positively regulates postnatal regression of retinal hyaloid vessels via suppression of VEGFR2/KDR activity, downstream of OPN5.

Subunit / interactions. Forms homo- and heterooligomers with DRD4. The interaction with DRD4 may modulate agonist-induced downstream signaling. Interacts with CADPS and CADPS2. Interacts with GPRASP1, PPP1R9B and CLIC6. Interacts with ARRB2. Interacts with HTR2A. Interacts with GNAI2 isoform sGi2, the interaction allows the creation of an intracellular pool of DRD2 that can be released to cell surface upon agonist stimulation. Interacts with DRD1. Interacts with KCNA2.

Subcellular location. Cell membrane. Golgi apparatus membrane.

Tissue specificity. Expressed in the anterior pituitary gland. Expressed in the anterior pituitary gland.

Post-translational modifications. Palmitoylated. Palmitoylation which is required for proper localization to the plasma membrane and stability of the receptor could be carried on by ZDHHC4, ZDHHC3 and ZDHHC8.

Polymorphism. Genetic variations in DRD2 may determine the genetic susceptibility to alcoholism [MIM:103780]. Genetic variations in DRD2 might be a protective factor against the development of withdrawal symptoms but might also be a risk factor in a highly burdened subgroup of alcoholics with a paternal and grandpaternal history of alcoholism and might contribute to suicide risk in alcoholics.

Similarity. Belongs to the G-protein coupled receptor 1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
P14416-1	1, D2(Long), D2A	yes
P14416-2	2, D2(Short), D2B
P14416-3	3, D2(Longer)

RefSeq proteins (2): NP_000786, NP_057658 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000929	Dopamine_rcpt	Family
IPR001922	Dopamine_D2_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (54 total): helix 14, topological domain 8, transmembrane region 7, sequence variant 4, mutagenesis site 4, glycosylation site 3, region of interest 2, site 2, disulfide bond 2, splice variant 2, chain 1, compositionally biased region 1, lipid moiety-binding region 1, sequence conflict 1, strand 1, turn 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
5AER	X-RAY DIFFRACTION	2.19
9BS9	ELECTRON MICROSCOPY	2.28
9BSB	ELECTRON MICROSCOPY	2.32
7JVR	ELECTRON MICROSCOPY	2.8
6CM4	X-RAY DIFFRACTION	2.87
8IRS	ELECTRON MICROSCOPY	3
6LUQ	X-RAY DIFFRACTION	3.1
7DFP	X-RAY DIFFRACTION	3.1
8TZQ	ELECTRON MICROSCOPY	3.2
8U02	ELECTRON MICROSCOPY	3.28
6VMS	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P14416-F1	72.49	0.37

Antibody-complex structures (SAbDab): 6 — 6VMS, 7DFP, 7JVR, 8IRS, 8TZQ, 9BSB

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 194 (important for receptor activation); 197 (important for receptor activation)

Post-translational modifications (1): 443

Disulfide bonds (2): 107–182, 399–401

Glycosylation sites (3): 5, 17, 23

Mutagenesis-validated functional residues (4):

Position	Phenotype
126	no effect on palmitoylation; no effect on localization to the plasma membrane.
244	no effect on palmitoylation; no effect on localization to the plasma membrane.
253	no effect on palmitoylation; no effect on localization to the plasma membrane.
443	decreased palmitoylation; decreased localization to the plasma membrane; decreased stability.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-390651	Dopamine receptors

MSigDB gene sets: 551 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_POTASSIUM_ION_TRANSPORT, GOBP_FOREBRAIN_NEURON_DEVELOPMENT, GOBP_G_PROTEIN_COUPLED_RECEPTOR_INTERNALIZATION, GOBP_MEMORY, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_EXCRETION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOBP_ACID_SECRETION, GOBP_COGNITION, MODULE_274, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_BEHAVIOR

GO Biological Process (121): temperature homeostasis (GO:0001659), response to hypoxia (GO:0001666), response to amphetamine (GO:0001975), nervous system process involved in regulation of systemic arterial blood pressure (GO:0001976), regulation of heart rate (GO:0002027), regulation of sodium ion transport (GO:0002028), G protein-coupled receptor internalization (GO:0002031), positive regulation of neuroblast proliferation (GO:0002052), positive regulation of receptor internalization (GO:0002092), intracellular calcium ion homeostasis (GO:0006874), autophagy (GO:0006914), adenylate cyclase-inhibiting dopamine receptor signaling pathway (GO:0007195), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), neuron-neuron synaptic transmission (GO:0007270), neuroblast proliferation (GO:0007405), axonogenesis (GO:0007409), synapse assembly (GO:0007416), sensory perception of smell (GO:0007608), long-term memory (GO:0007616), grooming behavior (GO:0007625), locomotory behavior (GO:0007626), adult walking behavior (GO:0007628), intracellular protein localization (GO:0008104), negative regulation of cell population proliferation (GO:0008285), associative learning (GO:0008306), visual learning (GO:0008542), response to xenobiotic stimulus (GO:0009410), response to light stimulus (GO:0009416), response to toxic substance (GO:0009636), response to iron ion (GO:0010039), regulation of dopamine secretion (GO:0014059), response to inactivity (GO:0014854), Wnt signaling pathway (GO:0016055), striatum development (GO:0021756), orbitofrontal cortex development (GO:0021769), cerebral cortex GABAergic interneuron migration (GO:0021853), adenohypophysis development (GO:0021984), negative regulation of cell migration (GO:0030336), peristalsis (GO:0030432), auditory behavior (GO:0031223)

GO Molecular Function (12): dopamine neurotransmitter receptor activity, coupled via Gi/Go (GO:0001591), G-protein alpha-subunit binding (GO:0001965), G protein-coupled receptor activity (GO:0004930), potassium channel regulator activity (GO:0015459), heterotrimeric G-protein binding (GO:0032795), dopamine binding (GO:0035240), ionotropic glutamate receptor binding (GO:0035255), identical protein binding (GO:0042802), dopamine neurotransmitter receptor activity (GO:0004952), signaling receptor binding (GO:0005102), protein binding (GO:0005515), protein-containing complex binding (GO:0044877)

GO Cellular Component (24): Golgi membrane (GO:0000139), acrosomal vesicle (GO:0001669), plasma membrane (GO:0005886), cilium (GO:0005929), lateral plasma membrane (GO:0016328), endocytic vesicle (GO:0030139), axon (GO:0030424), dendrite (GO:0030425), synaptic vesicle membrane (GO:0030672), sperm flagellum (GO:0036126), presynaptic membrane (GO:0042734), dendritic spine (GO:0043197), perikaryon (GO:0043204), axon terminus (GO:0043679), synapse (GO:0045202), postsynaptic membrane (GO:0045211), ciliary membrane (GO:0060170), G protein-coupled receptor complex (GO:0097648), non-motile cilium (GO:0097730), dopaminergic synapse (GO:0098691), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), Golgi apparatus (GO:0005794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Amine ligand-binding receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	3
receptor internalization	2
G protein-coupled dopamine receptor signaling pathway	2
G protein-coupled receptor signaling pathway	2
binding	2
bounding membrane of organelle	2
cellular anatomical structure	2
neuron projection	2
synaptic membrane	2
presynapse	2
postsynapse	2
cilium	2
multicellular organismal-level homeostasis	1
response to stress	1
response to decreased oxygen levels	1
response to amine	1
regulation of systemic arterial blood pressure	1
nervous system process	1
regulation of heart contraction	1
regulation of biological quality	1
sodium ion transport	1
regulation of metal ion transport	1
desensitization of G protein-coupled receptor signaling pathway	1
neuroblast proliferation	1
positive regulation of neurogenesis	1
regulation of neuroblast proliferation	1
positive regulation of neural precursor cell proliferation	1
regulation of receptor internalization	1
positive regulation of receptor-mediated endocytosis	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
phospholipase C activator activity	1
chemical synaptic transmission	1
generation of neurons	1
neural precursor cell proliferation	1
cell morphogenesis involved in neuron differentiation	1

Protein interactions and networks

STRING

2908 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DRD2	SLC6A3	Q01959	995
DRD2	ADORA2A	P29274	987
DRD2	ARRB2	P32121	963
DRD2	ANKK1	Q8NFD2	953
DRD2	DISC1	Q9NRI5	932
DRD2	COMT	P21964	924
DRD2	GNAO1	P09471	911
DRD2	SLC6A4	P31645	909
DRD2	CNR1	P21554	867
DRD2	SST	P01166	849
DRD2	GHRL	Q9UBU3	849
DRD2	TH	P07101	834
DRD2	SAG	P10523	827
DRD2	SSTR2	P30874	821
DRD2	SLC18A2	Q05940	814

IntAct

111 interactions, top by confidence:

A	B	Type	Score
DRD2	DRD2	psi-mi:“MI:2364”(proximity)	0.770
DRD2	DRD2	psi-mi:“MI:0915”(physical association)	0.770
ADORA2A	DRD2	psi-mi:“MI:2364”(proximity)	0.680
DRD2	ADORA2A	psi-mi:“MI:2364”(proximity)	0.680
DRD2	ADORA2A	psi-mi:“MI:0403”(colocalization)	0.680
DISC1	DRD2	psi-mi:“MI:0915”(physical association)	0.540
DRD2	DISC1	psi-mi:“MI:0407”(direct interaction)	0.540
DRD2	SIGMAR1	psi-mi:“MI:2364”(proximity)	0.520
DRD2	SIGMAR1	psi-mi:“MI:0403”(colocalization)	0.520
DRD2	SIGMAR1	psi-mi:“MI:0915”(physical association)	0.520
DRD2	SLC6A3	psi-mi:“MI:0915”(physical association)	0.520
SLC6A3	DRD2	psi-mi:“MI:0915”(physical association)	0.520
CNR1	DRD2	psi-mi:“MI:2364”(proximity)	0.470
CNR1	DRD2	psi-mi:“MI:0915”(physical association)	0.470
DRD2	Disc1	psi-mi:“MI:0407”(direct interaction)	0.440
DRD2	VDAC2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (129): DRD2 (Co-localization), DRD2 (Co-localization), DRD2 (PCA), DRD2 (Affinity Capture-MS), MSRA (Affinity Capture-MS), COLEC12 (Affinity Capture-MS), WDR45 (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), PRKCB (Affinity Capture-Western), CLIC6 (Two-hybrid), DRD2 (Affinity Capture-Western), DRD2 (FRET), NCS1 (Protein-peptide), NEFM (Two-hybrid), NEFM (Reconstituted Complex)

ESM2 similar proteins: B2RPY5, B3DM66, O02824, O73810, O77680, P14416, P15823, P18130, P18841, P18901, P19020, P20288, P21728, P21918, P25115, P30728, P31389, P35348, P35367, P35368, P41596, P42288, P42290, P42291, P43140, P50130, P52702, P53452, P53453, P53454, P60026, P61168, P61169, P97717, P97718, Q16950, Q18775, Q19084, Q24563, Q2YDN1

Diamond homologs: E7EM37, G3M4F8, O02213, O08890, O18935, O19014, O19025, O42384, O42385, O73810, O77715, O77723, O77830, P08908, P08909, P08913, P11614, P14416, P18825, P18871, P19020, P20288, P21917, P22086, P22270, P22909, P24628, P28221, P28222, P28334, P28335, P28564, P28566, P30545, P30728, P30729, P30939, P32304, P32305, P34968

SIGNOR signaling

46 interactions.

A	Effect	B	Mechanism
“Sumanirole maleate”	up-regulates	DRD2	“chemical activation”
DRD2	“up-regulates activity”	GNAI1	binding
DRD2	“up-regulates activity”	GNAI3	binding
DRD2	“up-regulates activity”	GNAO1	binding
DRD2	“up-regulates activity”	GNAZ	binding
dopamine	“up-regulates activity”	DRD2	“chemical activation”
aripiprazole	“up-regulates activity”	DRD2	“chemical activation”
7-[4-[4-(2,3-Dichlorophenyl)-1,4-diazepan-1-yl]butoxy]-3,4-dihydro-1H-quinolin-2-one	“up-regulates activity”	DRD2	“chemical activation”
7-[4-[4-(2,3-Dichlorophenyl)-1,4-diazepan-1-yl]butoxy]-3,4-dihydro-1H-1,8-naphthyridin-2-one	“up-regulates activity”	DRD2	“chemical activation”
5-{3-[4-(2,3-Dichlorophenyl)piperidin-1-yl]propoxy}-1,3-benzothiazole	“up-regulates activity”	DRD2	“chemical activation”
CDK5	“down-regulates activity”	DRD2	phosphorylation
NCS1	“down-regulates activity”	DRD2	binding
DRD2	“up-regulates activity”	GNB5	binding
TSPAN7	“down-regulates quantity”	DRD2	binding
GRK6	“down-regulates activity”	DRD2	phosphorylation
OXTR	“up-regulates activity”	DRD2	binding
lurasidone	“down-regulates activity”	DRD2	“chemical inhibition”
amisulpride	“down-regulates activity”	DRD2	“chemical inhibition”
bromocriptine	“up-regulates activity”	DRD2	“chemical activation”
clozapine	“down-regulates activity”	DRD2	“chemical inhibition”
chlorpromazine	“down-regulates activity”	DRD2	“chemical inhibition”
haloperidol	“down-regulates activity”	DRD2	“chemical inhibition”
apomorphine	“up-regulates activity”	DRD2	“chemical activation”
pimozide	“down-regulates activity”	DRD2	“chemical inhibition”
domperidone	“down-regulates activity”	DRD2	“chemical inhibition”
sulpiride	“down-regulates activity”	DRD2	“chemical inhibition”
Isoetharine	“up-regulates activity”	DRD2	“chemical activation”
“1-phospho-alpha-D-glucuronic acid”	“up-regulates activity”	DRD2	“chemical activation”
“2-N,6-N-Bis(2,3-dihydroxy-N-benzoyl)-L-serine amide”	“up-regulates activity”	DRD2	“chemical activation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 75 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
G alpha (i) signalling events	8	6.5×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	5	16.3×	1e-03
adenylate cyclase-activating G protein-coupled receptor signaling pathway	7	11.8×	3e-04
phospholipase C-activating G protein-coupled receptor signaling pathway	5	9.8×	7e-03
G protein-coupled receptor signaling pathway	13	7.0×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

175 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	46
Benign	48

Top pathogenic / likely-pathogenic (0)

SpliceAI

1412 predictions. Top by Δscore:

Variant	Effect	Δscore
11:113410918:CGC:C	acceptor_gain	1.0000
11:113412551:CTCA:C	donor_loss	1.0000
11:113412552:TCA:T	donor_loss	1.0000
11:113412554:A:AC	donor_gain	1.0000
11:113412554:A:AT	donor_loss	1.0000
11:113412554:AC:A	donor_gain	1.0000
11:113412555:C:CT	donor_gain	1.0000
11:113412555:CC:C	donor_gain	1.0000
11:113412555:CCG:C	donor_gain	1.0000
11:113416858:TGTAC:T	donor_loss	1.0000
11:113416859:GTAC:G	donor_loss	1.0000
11:113416860:TACC:T	donor_loss	1.0000
11:113416861:A:AT	donor_loss	1.0000
11:113416862:CCTG:C	donor_gain	1.0000
11:113417000:CTGCA:C	acceptor_loss	1.0000
11:113418024:CA:C	donor_loss	1.0000
11:113418026:C:CG	donor_loss	1.0000
11:113424363:CTAC:C	donor_loss	1.0000
11:113424364:TAC:T	donor_loss	1.0000
11:113424365:ACCT:A	donor_gain	1.0000
11:113424366:CCTC:C	donor_gain	1.0000
11:113424681:CT:C	acceptor_gain	1.0000
11:113424688:C:CT	acceptor_gain	1.0000
11:113424689:A:T	acceptor_gain	1.0000
11:113475071:CTTA:C	donor_loss	1.0000
11:113475072:TTA:T	donor_loss	1.0000
11:113475073:TAC:T	donor_loss	1.0000
11:113410916:CACGC:C	acceptor_gain	0.9900
11:113410919:GCCTG:G	acceptor_loss	0.9900
11:113410920:CCTGG:C	acceptor_loss	0.9900

AlphaMissense

2942 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:113410748:G:C	F437L	1.000
11:113410748:G:T	F437L	1.000
11:113410750:A:G	F437L	1.000
11:113410760:G:C	F433L	1.000
11:113410760:G:T	F433L	1.000
11:113410761:A:C	F433C	1.000
11:113410761:A:G	F433S	1.000
11:113410762:A:G	F433L	1.000
11:113410769:G:C	N430K	1.000
11:113410769:G:T	N430K	1.000
11:113410783:A:G	Y426H	1.000
11:113410785:A:T	I425N	1.000
11:113410791:G:C	P423R	1.000
11:113410791:G:T	P423H	1.000
11:113410792:G:A	P423S	1.000
11:113410793:G:C	N422K	1.000
11:113410793:G:T	N422K	1.000
11:113410802:G:C	S419R	1.000
11:113410802:G:T	S419R	1.000
11:113410804:T:G	S419R	1.000
11:113410805:G:C	N418K	1.000
11:113410805:G:T	N418K	1.000
11:113410815:C:T	G415D	1.000
11:113410816:C:G	G415R	1.000
11:113410889:G:C	F390L	1.000
11:113410889:G:T	F390L	1.000
11:113410891:A:G	F390L	1.000
11:113410892:G:C	F389L	1.000
11:113410892:G:T	F389L	1.000
11:113410894:A:G	F389L	1.000

dbSNP variants (sampled 300 via entrez): RS1000013665 (11:113463334 T>C), RS1000026823 (11:113474162 G>A), RS1000031874 (11:113474798 C>A), RS1000082310 (11:113475042 G>A), RS1000123040 (11:113416327 T>C), RS1000210894 (11:113445587 C>T), RS1000229570 (11:113417071 A>G), RS1000255535 (11:113427964 C>A), RS1000275641 (11:113457580 C>A,G,T), RS1000319532 (11:113450531 C>A,T), RS1000361595 (11:113462564 A>C), RS1000392716 (11:113462823 T>C), RS1000503237 (11:113456792 T>C), RS1000523005 (11:113416957 G>A), RS1000532000 (11:113444811 G>A)

Disease associations

OMIM: gene MIM:126450 | disease phenotypes: MIM:159900, MIM:181500

GenCC curated gene-disease

Disease	Classification	Inheritance
combined dystonia	Moderate	Autosomal dominant

Mondo (4): dystonic disorder (MONDO:0003441), myoclonic dystonia 11 (MONDO:0008044), schizophrenia (MONDO:0005090), combined dystonia (MONDO:0020065)

Orphanet (2): Myoclonus-dystonia syndrome (Orphanet:36899), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

11 total (12 of 11 shown, HPO-id order):

HPO	Term
HP:0000473	Torticollis
HP:0000716	Depression
HP:0000722	Compulsive behaviors
HP:0000739	Anxiety
HP:0001332	Dystonia
HP:0001336	Myoclonus
HP:0002356	Writer’s cramp
HP:0010531	Spinal myoclonus
HP:0012075	Personality disorder
HP:0025269	Panic attack
HP:0045084	Limb myoclonus
HP:0100753	Schizophrenia

GWAS associations

49 associations (top):

Study	Trait	p-value
GCST000083_3	Select biomarker traits	3.000000e-06
GCST000883_7	Response to antipsychotic treatment in schizophrenia (working memory)	5.000000e-07
GCST002187_9	Systolic blood pressure in sickle cell anemia	9.000000e-07
GCST002539_8	Schizophrenia	3.000000e-11
GCST002666_7	Interferon alpha levels in systemic lupus erythematosus	3.000000e-06
GCST002850_3	Information processing speed	9.000000e-07
GCST003770_48	Neuroticism	4.000000e-10
GCST003980_8	Sleep duration	5.000000e-07
GCST004521_280	Autism spectrum disorder or schizophrenia	5.000000e-09
GCST004860_34	Alcoholic chronic pancreatitis	6.000000e-06
GCST004946_121	Schizophrenia	5.000000e-11
GCST005232_102	Neuroticism	2.000000e-18
GCST005951_69	Body mass index	3.000000e-10
GCST006613_133	Triglycerides	2.000000e-08
GCST006803_30	Schizophrenia	2.000000e-12
GCST007201_124	Schizophrenia	1.000000e-10
GCST007201_207	Schizophrenia	5.000000e-10
GCST007328_19	Alcohol consumption (drinks per week)	2.000000e-13
GCST007576_287	Chronotype	2.000000e-09
GCST007709_293	General factor of neuroticism	7.000000e-14
GCST007709_294	General factor of neuroticism	3.000000e-12
GCST007709_295	General factor of neuroticism	4.000000e-12
GCST007709_296	General factor of neuroticism	3.000000e-10
GCST007709_298	General factor of neuroticism	3.000000e-09
GCST007709_299	General factor of neuroticism	3.000000e-09
GCST007709_302	General factor of neuroticism	2.000000e-08
GCST008259_14	Alcohol use disorder	3.000000e-11
GCST008259_20	Alcohol use disorder	1.000000e-13
GCST008259_25	Alcohol use disorder	2.000000e-08
GCST008357_19	Mood instability	3.000000e-09

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0004789	atrial natriuretic factor measurement
EFO:0004335	short-term memory
EFO:0006335	systolic blood pressure
EFO:0006517	interferon alpha measurement
EFO:0004363	information processing speed
EFO:0007660	neuroticism measurement
EFO:0004340	body mass index
EFO:0004530	triglyceride measurement
EFO:0008328	chronotype measurement
EFO:0009458	alcohol use disorder measurement
EFO:0008475	mood instability measurement
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0006527	smoking status measurement
EFO:0004319	smoking cessation
EFO:0009589	worry measurement
EFO:0009592	social interaction measurement
EFO:0007645	longitudinal alcohol consumption measurement
EFO:0009863	anxiety measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D020821	Dystonic Disorders	C10.228.662.300

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (10): CHEMBL2095169 (SELECTIVITY GROUP), CHEMBL2095396 (SELECTIVITY GROUP), CHEMBL2096905 (PROTEIN FAMILY), CHEMBL2111341 (SELECTIVITY GROUP), CHEMBL2111460 (SELECTIVITY GROUP), CHEMBL2111468 (SELECTIVITY GROUP), CHEMBL217 (SINGLE PROTEIN), CHEMBL2331075 (PROTEIN FAMILY), CHEMBL3038478 (PROTEIN COMPLEX), CHEMBL4296096 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

298 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 826,709 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1201087	CABERGOLINE	4	12,778
CHEMBL53	APOMORPHINE	4	25,813
CHEMBL54	HALOPERIDOL	4	60,883
CHEMBL589	ROPINIROLE	4	21,493
CHEMBL59	DOPAMINE	4	217,028
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1065	METHYSERGIDE	4	8,455
CHEMBL1071	OXAPROZIN	4	51,044
CHEMBL1085	ACETOPHENAZINE	4	5,134
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL1108	DROPERIDOL	4	16,888
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1117	IDARUBICIN	4	136,065
CHEMBL114	SAQUINAVIR	4	39,899
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1172	DESLORATADINE	4	19,720
CHEMBL1175	DULOXETINE	4	28,527
CHEMBL1200384	BETAMETHASONE DIPROPIONATE	4	12,700
CHEMBL1200438	TIOCONAZOLE	4
CHEMBL1200492	NEFAZODONE HYDROCHLORIDE	4
CHEMBL1200517	DIHYDROERGOTAMINE MESYLATE	4
CHEMBL1200618	FEXOFENADINE HYDROCHLORIDE	4
CHEMBL1200809	AZELASTINE HYDROCHLORIDE	4
CHEMBL1200986	HALOPERIDOL DECANOATE	4
CHEMBL1201	THIOTHIXENE	4
CHEMBL1201192	ARMODAFINIL	4
CHEMBL1201203	BENZTROPINE	4
CHEMBL1201210	PROPIOMAZINE	4

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

62 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1076560	Efficacy	3	olanzapine	Schizophrenia
rs1076560	Efficacy	3	rasagiline	Parkinson Disease
rs1076560	Other	3	opioids	Heroin Dependence;Opioid-Related Disorders
rs1076560	Toxicity	3	cocaine	Cocaine dependence
rs1079596	Toxicity	3	opioids	Opioid-Related Disorders
rs1079597	Efficacy	3	amisulpride	Schizophrenia
rs1079597	Efficacy	3	prochlorperazine	Nausea
rs1079598	Toxicity	3	antipsychotics;clozapine;olanzapine	Schizophrenia
rs1124491	Toxicity	3	antipsychotics	Psychotic Disorder
rs1124493	Other	3	olanzapine
rs1125394	Other	3	cocaine	Cocaine dependence
rs1125394	Toxicity	3	opioids	Opioid-Related Disorders
rs12364283	Other	3	amphetamine
rs12364283	Toxicity	3	heroin	Heroin Dependence
rs1799732	Efficacy	3	bupropion	Tobacco Use Disorder
rs1799732	Efficacy	3	nicotine	Tobacco Use Disorder
rs1799732	Toxicity	3	antipsychotics	Psychotic Disorder
rs1799732	Toxicity	3	levodopa	Parkinson Disease
rs1799732	Toxicity	3	ethanol	Alcohol abuse
rs1799732	Efficacy	3	risperidone	Schizophrenia
rs1799732	Efficacy	3	olanzapine	Schizophrenia
rs1799732	Efficacy	3	bromperidol
rs1799732	Efficacy	3	nemonapride
rs1799978	Dosage	3	methadone	Heroin Dependence
rs1799978	Efficacy	3	olanzapine	Schizophrenia
rs1799978	Toxicity	3	risperidone	Hyperprolactinemia
rs1799978	Efficacy	4	risperidone	Schizophrenia
rs1800497	Toxicity	3	nicotine	Tobacco Use Disorder
rs1800497	Efficacy	3	prochlorperazine	Nausea
rs1800497	Toxicity	3	opioids	Opioid-Related Disorders
rs1800497	Toxicity	3	nicotine
rs1800497	Toxicity	3	ethanol	Alcohol abuse
rs1800497	Efficacy	3	bupropion;naltrexone	Obesity
rs1800497	Toxicity	3	risperidone	Autism;Hyperprolactinemia;Schizophrenia
rs1800497	Efficacy	4	risperidone	Autism;Schizophrenia
rs1800497	Toxicity	3	ethanol	Alcohol abuse;Death
rs1800497	Toxicity	3	ethanol	Alcohol abuse;Substance-Related Disorders
rs1800497	Dosage	3	ethanol

PharmGKB variants

39 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6275	DRD2	3	2.00	4	olanzapine;methadone;Analgesics;Antiinflammatory agents;non-steroids;Ergot alkaloids;opioids;sumatriptan;rizatriptan
rs6277	DRD2	3	2.00	4	antipsychotics;clozapine;olanzapine;nicotine;aripiprazole;methadone
rs6279	DRD2	3	1.75	1	olanzapine
rs1076560	DRD2	3	5.50	4	olanzapine;cocaine;rasagiline;opioids
rs1076563	DRD2		0.00	0
rs1079597	DRD2	3	2.00	2	prochlorperazine;amisulpride
rs1079598	DRD2	3	2.25	1	antipsychotics;clozapine;olanzapine
rs1110976	DRD2		0.00	0
rs1124493	DRD2	3	1.75	1	olanzapine
rs1125394	DRD2	3	3.00	2	opioids;cocaine
rs1799732	DRD2	3	3.25	9	levodopa;antipsychotics;bupropion;nicotine;ethanol;risperidone;olanzapine;bromperidol;nemonapride
rs1799978	DRD2	3	2.75	4	risperidone;olanzapine;methadone
rs1800497	ANKK1, DRD2	3	4.50	20	risperidone;nemonapride;disulfiram;opioids;nicotine;prochlorperazine;ethanol;olanzapine;valproic acid;aripiprazole
rs1801028	DRD2		0.00	0
rs2234689	DRD2		0.00	0
rs2283265	DRD2	3	4.50	5	disulfiram;methadone;methylphenidate;cocaine;rasagiline
rs2440390	DRD2	3	2.00	1	olanzapine
rs2514218	DRD2	3	1.75	2	aripiprazole;aripiprazole;risperidone
rs2587548	DRD2		0.00	0
rs2734833	DRD2	3	0.00	1	Selective serotonin reuptake inhibitors
rs2734841	DRD2	3	1.75	1	olanzapine
rs2734842	DRD2	3	1.75	1	olanzapine
rs4436578	DRD2	3	3.25	1	clozapine;olanzapine;risperidone
rs4460839	DRD2, MIR4301	3	0.00	1	Selective serotonin reuptake inhibitors
rs4648317	DRD2		0.00	0
rs7131056	DRD2		0.00	0
rs12364283	DRD2	3	3.50	2	amphetamine;heroin
rs1124491	DRD2	3	3.00	1	antipsychotics
rs1800498	DRD2		0.00	0
rs4274224	DRD2		0.00	0
rs7131440	DRD2		0.00	0
rs7122246	DRD2		0.00	0
rs17601612	DRD2		0.00	0
rs1079596	DRD2	3	2.00	1	opioids
rs4648318	DRD2		0.00	0
rs2075652	DRD2		0.00	0
rs4936274	DRD2		0.00	0
rs11214607	DRD2		0.00	0
rs12574471	DRD2		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Dopamine receptors

Most potent curated ligand interactions (88 total), top 25:

Ligand	Action	Affinity	Parameter
[3H]nemonapride	Antagonist	10.9	pKd
[3H]N-methylspiperone	Antagonist	10.7	pKi
benperidol	Antagonist	10.57	pKi
rotigotine	Agonist	10.22	pKi
[3H]spiperone	Antagonist	10.2	pKd
blonanserin	Antagonist	9.85	pKi
pipotiazine	Antagonist	9.7	pKi
perphenazine	Antagonist	9.59	pKi
brexpiprazole	Partial agonist	9.52	pKi
lisuride	Partial agonist	9.5	pKi
spiperone	Antagonist	9.4	pKi
risperidone	Antagonist	9.36	pKi
perospirone	Antagonist	9.22	pKi
eticlopride	Antagonist	9.2	pKi
cabergoline	Partial agonist	9.2	pKi
terguride	Partial agonist	9.1	pKi
trifluoperazine	Antagonist	9.02	pKi
asenapine	Antagonist	8.92	pKi
sertindole	Antagonist	8.92	pKi
[3H]raclopride	Antagonist	8.9	pKd
(-)-N-porphynorapomorphine	Full agonist	8.9	pKi
fluphenazine	Antagonist	8.84	pKi
flupentixol	Antagonist	8.82	pKi
haloperidol	Antagonist	8.8	pKi
pimozide	Antagonist	8.8	pKi

Binding affinities (BindingDB)

1575 measured of 1682 human assays (1749 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
EPIDEPRIDE	KI	0.01 nM
1-[3-(2-methylsulfonylphenothiazin-10-yl)propyl]piperidine-4-carboxamide	KI	0.07 nM	US-9132134: Methods for treating GI tract disorders
UNC10107969	EC50	0.1 nM	US-9156822: Functionally selective ligands of dopamine D2 receptors
NSC_104911	KI	0.1 nM
roxindole	KI	0.11 nM
CAS_18426-20-5	KI	0.12 nM
(2,3-Dimethoxy-phenyl)-{1-[2-(4-fluoro-phenyl)-ethyl]-piperidin-4-yl}-methanol(MDL 100907)	KI	0.14 nM
3,3-diethyl-1-[(4R,7R)-6-methyl-6,11-diazatetracyclo[7.6.1.0^{2,7}.0^{12,16}]hexadeca-1(15),2,9,12(16),13-pentaen-4-yl]urea	KI	0.15 nM
UNC10107968	EC50	0.2 nM	US-9156822: Functionally selective ligands of dopamine D2 receptors
ethyl N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]carbamate	KI	0.2 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
CAS_39860-99-6	KI	0.2 nM
CAS_53772-85-3	KI	0.2 nM
CAS_14759-06-9	KI	0.2 nM
6-(2-(4-(benzo[b]thiophen-4-yl)piperidin-1-yl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one	EC50	0.223 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
5-(2-(4-(6-fluorobenzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)indolin-2-one	EC50	0.235 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
Ethyl 2-(4-(3-(5-fluoro-1H-indol-3-yl)propyl)piperazin-1-yl)-4-methylthiazole-5-carboxylate	KI	0.27 nM	US-9598401: Substituted heteroaryl compounds and methods of use thereof
Ethyl 2-(4-(3-(5-cyano-1H-indol-3-yl)propyl)piperazin-1-yl)-4-methylthiazole-5-carboxylate	KI	0.3 nM	US-9598401: Substituted heteroaryl compounds and methods of use thereof
(S,S)-reboxetine	KI	0.3 nM
(trans) 2-{4-[3-(4-Fluoro-phenyl)-6-trifluoromethyl-indan-1-yl]-piperazin-1-yl}-ethanol	KI	0.3 nM
(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2-(furan-3-yl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho-[2,1-c]pyran-7-carboxylic acid methyl ester	EC50	0.3 nM
CAS_51152-91-1	KI	0.3 nM
5-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)benzo[d]thiazol-2-amine	EC50	0.379 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
7-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)benzo[d]thiazol-2-amine	EC50	0.397 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
UNC10108010	EC50	0.4 nM	US-9156822: Functionally selective ligands of dopamine D2 receptors
UNC10108018	EC50	0.4 nM	US-9156822: Functionally selective ligands of dopamine D2 receptors
NSC_92178	KI	0.45 nM
2-Chlor-11-(2-dimethylaminoaethoxy)-dibenzo(b,f)-thiepin	KI	0.5 nM
3,5-Dichloro-N-(1-ethyl-pyrrolidin-2-ylmethyl)-2-hydroxy-6-methoxy-benzamide(Raclopride)	KI	0.5 nM
UNC10108016	EC50	0.5 nM	US-9156822: Functionally selective ligands of dopamine D2 receptors
NSC_122245	KI	0.5 nM
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-1H-pyrrole-2-carboxamide	KI	0.52 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
phenyl N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]carbamate	KI	0.58 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
6-(2-(4-(6-fluorobenzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one	EC50	0.599 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N-methylpropan-1-amine	KI	0.6 nM
N-(5-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)benzo[d]thiazol-2-yl)acetamide	EC50	0.602 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
6-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one	EC50	0.626 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
6-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-2H-benzo[b][1,4]thiazin-3(4H)-one	EC50	0.68 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
8-chloro-6-piperazin-1-ylbenzo[b][1,4]benzothiazepine	KI	0.7 nM	US-8653257: Dibenzothiazepine derivatives and uses thereof—424
(3aR,4R,6aS)-4-(5-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)pentyl)tetrahydro-1H-thieno[3,4-d]imidazol-2(3H)-one	EC50	0.75 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
4-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)benzo[d]thiazol-2-amine	EC50	0.761 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
6-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-8-fluoro2H-benzo[b][1,4]oxazin-3(4H)-one	EC50	0.766 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
5-(2-(4-(2-fluorobenzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)indolin-2-one	EC50	0.77 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
N-(7-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)benzo[d]thiazol-2-yl)acetamide	EC50	0.787 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-5-chloro-1-benzothiophene-2-sulfonamide	KI	0.79 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
benzyl N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]carbamate	KI	0.79 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
7-(2-(4-(2,3-dihydrobenzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)quinolin-2(1H)-one	EC50	0.824 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
UNC10108019	EC50	0.9 nM	US-9156822: Functionally selective ligands of dopamine D2 receptors
SDZ-208-912	KI	0.9 nM
7-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-3,4-dihydroquinolin-2(1H)-one	EC50	0.926 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-5-methoxy-1-benzothiophene-2-sulfonamide	KI	0.97 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	EC50	0.01	nM	LISURIDE
10.83	Kd	0.0149	nM	PRAMIPEXOLE
10.83	Kd	0.0149	nM	CHEMBL5207281
10.83	Kd	0.0149	nM	CHEMBL5183205
10.83	Kd	0.0149	nM	CHEMBL5200771
10.83	Kd	0.0149	nM	CHEMBL5204599
10.83	Kd	0.0149	nM	CHEMBL5206565
10.83	Kd	0.0149	nM	CHEMBL5178472
10.83	Kd	0.0149	nM	CHEMBL5208845
10.83	Kd	0.0149	nM	CHEMBL5201074
10.83	Kd	0.0149	nM	CHEMBL5184911
10.83	Kd	0.0149	nM	CHEMBL5180504
10.83	Kd	0.0149	nM	CHEMBL5202592
10.83	Kd	0.0149	nM	CHEMBL5198795
10.83	Kd	0.0149	nM	CHEMBL5176229
10.70	EC50	0.01995	nM	CHEMBL134807
10.70	Ki	0.02	nM	FALLYPRIDE
10.57	Ki	0.027	nM	BENPERIDOL
10.52	Kd	0.03	nM	CHEMBL1774386
10.51	Ki	0.031	nM	CHEMBL156164
10.50	EC50	0.03162	nM	CHEMBL3115575
10.40	Ki	0.04	nM	BUTACLAMOL
10.40	EC50	0.03981	nM	R-N-PROPYLNORAPOMORPHINE
10.40	EC50	0.04	nM	R-N-PROPYLNORAPOMORPHINE
10.40	Ki	0.04	nM	BIFEPRUNOX
10.40	Ki	0.04	nM	CHEMBL317488
10.30	EC50	0.05012	nM	CHEMBL3115585
10.30	Ki	0.05	nM	CHEMBL156651
10.28	Ki	0.05248	nM	CHEMBL4451384
10.26	Kd	0.05495	nM	CHEMBL4451384
10.24	Ki	0.05754	nM	CHEMBL1257382
10.24	Ki	0.0575	nM	CHEMBL1257382
10.22	Ki	0.06	nM	SPIPERONE
10.22	Ki	0.06	nM	ROTIGOTINE
10.22	Ki	0.06	nM	CHEMBL317488
10.19	Ki	0.064	nM	CHEMBL156164
10.18	Ki	0.066	nM	CANNABIDIOL
10.17	Ki	0.067	nM	CHEMBL156651
10.15	Ki	0.07	nM	METOPIMAZINE
10.15	Kd	0.07	nM	MESPIPERONE
10.15	Ki	0.071	nM	CHEMBL156164
10.15	Ki	0.07	nM	CHEMBL1813595
10.14	Kd	0.07244	nM	MESPIPERONE
10.13	Ki	0.07413	nM	CHEMBL538542
10.12	Ki	0.075	nM	CHEMBL538542
10.07	Ki	0.086	nM	ETICLOPRIDE
10.05	Ki	0.089	nM	SPIPERONE
10.05	Ki	0.09	nM	CHEMBL156651
10.05	Ki	0.09	nM	CHEMBL317488
10.04	IC50	0.092	nM	CHEMBL5900385

PubChem BioAssay actives

3324 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-(3-fluoropropyl)-2,3-dimethoxy-N-[[(2S)-1-prop-2-enylpyrrolidin-2-yl]methyl]benzamide	2141241: Binding affinity to D2 receptor (unknown origin)	ki	<0.0001	uM
Pramipexole	1895202: Displacement of [3H]N-methylspiperone from human D2 long receptor stably expressed in HEK293T cells co-expressing luciferase and CEK incubated for 140 mins by radioligand competition binding based assay	kd	<0.0001	uM
(3S,6R,8aR)-5-oxo-1’-[(2S)-pyrrolidine-2-carbonyl]spiro[3,7,8,8a-tetrahydro-2H-[1,3]thiazolo[3,2-a]pyridine-6,2’-pyrrolidine]-3-carboxamide	61461: Inhibitor constant of compound for high affinity component of [3H]spiroperidol/N-propylnorapomorphine binding to Dopamine receptor D2 in absence of Gpp(NH)p (pretreatment with 100 nM of compound)	ki	0.0001	uM
4-[(1S,5R)-3-(4-chlorophenyl)-3-hydroxy-8-azabicyclo[3.2.1]octan-8-yl]-1-(4-fluorophenyl)butan-1-one	1616723: Displacement of PPHT-red from SNAP-tagged human D2LR expressed in CHOK1 cell membranes by TR-FRET assay	kd	0.0001	uM
4-chloro-11-methyl-11-azatricyclo[12.4.0.03,8]octadeca-1(18),3(8),4,6,14,16-hexaen-5-ol	261576: Inhibition of D2L dopamine receptor in HEK 293 cells by intracellular calcium assay	ki	0.0001	uM
8-[4-(4-fluorophenyl)-4-oxobutyl]-3-methyl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one	1143583: Displacement of [3H]N-methylspiperone from human dopamine D2 receptor expressed in HEK293 cells after 1 hr by liquid scintillation counting analysis	ki	0.0001	uM
(6aR)-6-propyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-10,11-diol;hydrochloride	1067729: Binding affinity to high-affinity state of D2L receptor (unknown origin) expressed in CHO cell membranes	ki	0.0001	uM
2-(4-ethylpiperazin-1-yl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine	239248: In vitro binding affinity against recombinant human dopamine receptor D2L in human liver microsomes	ki	0.0001	uM
6-[propyl(2-thiophen-3-ylethyl)amino]-5,6,7,8-tetrahydronaphthalen-1-ol	64502: Binding affinity was evaluated by calculating competition for [3H]N-0437 binding on Dopamine receptor D2L of CHO K-1 cells	ki	0.0001	uM
6-[4-[[(2S)-5-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]-propylamino]butoxy]pyrazolo[1,5-a]pyridine-3-carbaldehyde	1442576: Agonist activity at N-terminal flag-tagged D2S receptor (unknown origin) expressed in HEK293 cells coexpressing renilla luciferase 2-tagged GalphaoA after 10 mins by BRET assay	ec50	0.0001	uM
5-[4-[[(2S)-5-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]-propylamino]butoxy]pyrazolo[1,5-a]pyridine-3-carbaldehyde	1442576: Agonist activity at N-terminal flag-tagged D2S receptor (unknown origin) expressed in HEK293 cells coexpressing renilla luciferase 2-tagged GalphaoA after 10 mins by BRET assay	ec50	0.0001	uM
(6S)-6-[propyl(4-pyrazolo[1,5-a]pyridin-5-yloxybutyl)amino]-5,6,7,8-tetrahydronaphthalen-1-ol	1442576: Agonist activity at N-terminal flag-tagged D2S receptor (unknown origin) expressed in HEK293 cells coexpressing renilla luciferase 2-tagged GalphaoA after 10 mins by BRET assay	ec50	0.0001	uM
4-[3-[4-(2-oxo-3H-1,3-benzoxazol-7-yl)piperazin-1-yl]propyl]-1,4-benzoxazin-3-one	1433091: Agonist activity at human dopamine D2L receptor expressed in F1pIn CHO cells assessed as increase in forskolin-mediated cAMP accumulation incubated for 30 mins by AlphaScreen assay	ec50	0.0001	uM
(6S)-6-[propyl(4-pyrazolo[1,5-a]pyridin-6-yloxybutyl)amino]-5,6,7,8-tetrahydronaphthalen-1-ol	1442576: Agonist activity at N-terminal flag-tagged D2S receptor (unknown origin) expressed in HEK293 cells coexpressing renilla luciferase 2-tagged GalphaoA after 10 mins by BRET assay	ec50	0.0001	uM
3-[4-[2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl]cyclohexyl]-1,1-dimethylurea	1933510: Partial agonist activity at human D2 receptor assessed as increase in cAMP accumulation	ec50	0.0002	uM
(6S)-6-[2-[4-(9H-carbazol-2-yl)piperazin-1-yl]ethyl-propylamino]-5,6,7,8-tetrahydronaphthalen-1-ol	1873153: Agonist activity at dopamine D2 receptor (unknown origin) assessed as increase in GTPgammaS binding	ec50	0.0002	uM
(6S)-6-[4-[3-[(E)-hydroxyiminomethyl]pyrazolo[1,5-a]pyridin-6-yl]oxybutyl-propylamino]-5,6,7,8-tetrahydronaphthalen-1-ol	1442576: Agonist activity at N-terminal flag-tagged D2S receptor (unknown origin) expressed in HEK293 cells coexpressing renilla luciferase 2-tagged GalphaoA after 10 mins by BRET assay	ec50	0.0002	uM
(6S)-6-[4-[3-[(Z)-hydroxyiminomethyl]pyrazolo[1,5-a]pyridin-5-yl]oxybutyl-propylamino]-5,6,7,8-tetrahydronaphthalen-1-ol	1442576: Agonist activity at N-terminal flag-tagged D2S receptor (unknown origin) expressed in HEK293 cells coexpressing renilla luciferase 2-tagged GalphaoA after 10 mins by BRET assay	ec50	0.0002	uM
(3aS,9aR)-1-prop-2-enyl-2,3,3a,4,9,9a-hexahydrobenzo[f]indol-5-ol	62743: Compound was tested for agonistic activity against D2 receptor from cloned CHO cells, used [3H]U-86170 as radioligand	ki	0.0003	uM
7-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butoxy]-3,4-dihydro-1H-quinolin-2-one	698938: Displacement of [3H]N-methylspiperone from human D2L receptor expressed in CHO cells after 1.5 hrs by microbeta counting method	ki	0.0003	uM
7-[4-[4-(2-fluorophenyl)piperazin-1-yl]butoxy]-3,4-dihydro-1H-quinolin-2-one	698937: Agonist activity at human D2L receptor expressed in HEK293T cells coexpressing Gi subunit assessed as inhibition of isoproterenol-stimulated cAMP production by luminescence assay	ec50	0.0003	uM
Brexpiprazole	1517960: Displacement of [3H]-raclopride from human D2L receptor expressed in HEK293 cells incubated for 1 hr by liquid scintillation counting method	ki	0.0003	uM
N-[4-[methyl-[(10R)-2-oxo-1,3-diazatricyclo[6.3.1.04,12]dodeca-4,6,8(12)-trien-10-yl]amino]butyl]-1H-indole-2-carboxamide	1443616: Agonist activity at human dopamine D2 receptor expressed in HEK293 cells assessed as cAMP inhibition by BRET assay	ec50	0.0003	uM
4-[3-(4-chlorophenyl)-3-hydroxy-8-azabicyclo[3.2.1]octan-8-yl]-1-(4-fluorophenyl)butan-1-one	1185963: Displacement of [3H]N-methylspiperone from human dopamine D2 receptor by liquid scintillation counting	ki	0.0003	uM
4-[5-[[(2S)-5-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]-propylamino]pentyl]benzene-1,2-diol	1630278: Agonist activity at human D2 dopamine receptor expressed in CHO cells by [35S]GTPgammaS binding assay	ec50	0.0003	uM
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-N-methylthiophene-2-sulfonamide	1332824: Displacement of [3H]spiperone from recombinant human D2L receptor expressed in CHO cell membranes after 60 mins by scintillation counting method	ki	0.0003	uM
4-[4-(2,3-dichlorophenyl)piperazin-1-yl]-N-(3-formylpyrazolo[1,5-a]pyridin-5-yl)butanamide	1442559: Displacement of [3H]spiperone from human Dopamine D2L receptor expressed in CHO cell membranes after 2 hrs by scintillation counting analysis	ki	0.0003	uM
(6aR)-2-fluoro-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-10,11-diol	61063: Compound was evaluated for the ability to displace [3H]spiperone at dopamine receptor in porcine anterior pituitary gland as high affinity state	kd	0.0004	uM
7-[4-(4-phenylpiperazin-1-yl)butoxy]-3,4-dihydro-1H-quinolin-2-one	698935: Agonist activity at D2L receptor in human HTLA cells assessed as beta arrestin recruitment at 6 uM after 18 hrs by luminescence assay	ec50	0.0004	uM
(NE)-N-[[6-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butoxy]pyrazolo[1,5-a]pyridin-3-yl]methylidene]hydroxylamine	1442568: Agonist activity at human Dopamine D2S receptor expressed in HEK293T cell membranes coexpressing Galphai2 incubated for 30 mins measured after 75 mins by [35S]GTPgammaS binding assay	ec50	0.0004	uM
(3aS,9aR)-1-propyl-2,3,3a,4,9,9a-hexahydrobenzo[f]indol-5-ol	62743: Compound was tested for agonistic activity against D2 receptor from cloned CHO cells, used [3H]U-86170 as radioligand	ki	0.0005	uM
5-[4-(4-phenyl-3,6-dihydro-2H-pyridin-1-yl)but-1-ynyl]pyridin-2-amine	62757: In vivo Dopamine receptor D2 mitogenesis measured as [3H]thymidine incorporation in CHO p-5 cells expressing human D2 receptors	ec50	0.0005	uM
6-(propylamino)-5,6,7,8-tetrahydronaphthalen-1-ol	64502: Binding affinity was evaluated by calculating competition for [3H]N-0437 binding on Dopamine receptor D2L of CHO K-1 cells	ki	0.0005	uM
4-[4-(4-phenyl-3,6-dihydro-2H-pyridin-1-yl)but-1-ynyl]aniline	62749: Compound was evaluated for effective concentration in vivo for Dopamine receptor D2 mitogenesis. (95% confidence intervals)	ec50	0.0005	uM
4-[3-(1-butyltriazol-4-yl)propoxy]-N-[4-[[(2S)-5-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]-propylamino]butyl]-3-methoxybenzamide	1225546: Displacement of [3H]spiperone from human dopamine D2L receptor transfected in CHO cells after 1 hr by scintillation counting analysis	ki	0.0005	uM
6-[2-phenylethyl(propyl)amino]-5,6,7,8-tetrahydronaphthalen-1-ol	64502: Binding affinity was evaluated by calculating competition for [3H]N-0437 binding on Dopamine receptor D2L of CHO K-1 cells	ki	0.0005	uM
3-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-1-ethyl-1-methylurea	1332824: Displacement of [3H]spiperone from recombinant human D2L receptor expressed in CHO cell membranes after 60 mins by scintillation counting method	ki	0.0005	uM
8-hydroxy-5-[4-[4-[3-[(E)-hydroxyiminomethyl]pyrazolo[1,5-a]pyridin-5-yl]oxybutyl]piperazin-1-yl]-1H-quinolin-2-one	1464177: Displacement of [3H]spiperone from human D2SR expressed in CHO cell membranes	ki	0.0005	uM
4-[4-(2,3-dichlorophenyl)piperazin-1-yl]-N-[3-[(Z)-hydroxyiminomethyl]pyrazolo[1,5-a]pyridin-5-yl]butanamide	1442556: Displacement of [3H]spiperone from human Dopamine D2S receptor expressed in CHO cell membranes after 2 hrs by scintillation counting analysis	ki	0.0005	uM
N-(3-cyanopyrazolo[1,5-a]pyridin-5-yl)-4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butanamide	1442556: Displacement of [3H]spiperone from human Dopamine D2S receptor expressed in CHO cell membranes after 2 hrs by scintillation counting analysis	ki	0.0005	uM
N-[3-[(Z)-hydroxyiminomethyl]pyrazolo[1,5-a]pyridin-5-yl]-4-[4-(2-methoxyphenyl)piperazin-1-yl]butanamide	1442556: Displacement of [3H]spiperone from human Dopamine D2S receptor expressed in CHO cell membranes after 2 hrs by scintillation counting analysis	ki	0.0005	uM
4-[4-(4-chlorophenyl)-4-hydroxy-1,4-azasilinan-1-yl]-1-(4-fluorophenyl)butan-1-one	711580: Inhibition of human dopamine D2 receptor	ki	0.0006	uM
N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]-5-phenylpyridin-2-amine	502573: Displacement of [3H]spiperone from human dopamine D2S receptor expressed in HEK293 cells	ki	0.0006	uM
N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]quinolin-2-amine	502573: Displacement of [3H]spiperone from human dopamine D2S receptor expressed in HEK293 cells	ki	0.0006	uM
N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]-4-phenylpyridin-2-amine	502573: Displacement of [3H]spiperone from human dopamine D2S receptor expressed in HEK293 cells	ki	0.0006	uM
6,16-dimethoxy-11-methyl-11-azatricyclo[12.4.0.03,8]octadeca-1(14),3(8),4,6,15,17-hexaene	261576: Inhibition of D2L dopamine receptor in HEK 293 cells by intracellular calcium assay	ki	0.0006	uM
1-[(2-bromophenyl)methyl]-N-[5-[4-(2-methoxyphenyl)piperazin-1-yl]pentyl]-5-methyltriazole-4-carboxamide	1245089: Displacement of [3H]spiperone from human dopamine D2L receptor expressed in CHO cell membranes by radioligand competition binding assay	ki	0.0006	uM
N-(3-cyanopyrazolo[1,5-a]pyridin-5-yl)-4-[4-(2-methoxyphenyl)piperazin-1-yl]butanamide	1442556: Displacement of [3H]spiperone from human Dopamine D2S receptor expressed in CHO cell membranes after 2 hrs by scintillation counting analysis	ki	0.0006	uM
5-[4-[4-(8-hydroxy-2-oxo-1H-quinolin-5-yl)piperazin-1-yl]butoxy]pyrazolo[1,5-a]pyridine-3-carbaldehyde	1464177: Displacement of [3H]spiperone from human D2SR expressed in CHO cell membranes	ki	0.0006	uM
7-[methyl(propyl)amino]-5,6,7,8-tetrahydronaphthalen-2-ol	64502: Binding affinity was evaluated by calculating competition for [3H]N-0437 binding on Dopamine receptor D2L of CHO K-1 cells	ki	0.0007	uM

CTD chemical–gene interactions

92 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Risperidone	affects response to substance, increases response to substance, affects binding, decreases activity	12
Olanzapine	increases response to substance, affects activity, affects binding, decreases activity	6
Clozapine	affects response to substance, increases response to substance, affects binding, affects cotreatment, increases secretion	6
Cocaine	affects binding, affects reaction, decreases expression, increases response to substance	6
Haloperidol	decreases reaction, affects binding, affects activity, increases expression	5
Quinpirole	affects binding, decreases reaction, increases abundance, increases activity, decreases transport (+4 more)	5
Methamphetamine	increases response to substance, decreases expression	4
Raclopride	affects binding, affects reaction, affects cotreatment, increases reaction	4
Dopamine	affects binding, increases reaction, affects localization, affects cotreatment, increases activity	3
Spiperone	affects binding, decreases reaction	3
7-(N,N-dipropylamino)-5,6,7,8-tetrahydronaphtho(2,3-b)dihydro-2,3-furan	affects binding, decreases activity, increases activity	2
Bromocriptine	affects expression, increases response to substance	2
Chlorpromazine	decreases activity, decreases response to substance	2
Metoclopramide	affects binding, decreases activity	2
Sulpiride	increases activity, affects binding, decreases reaction, decreases transport	2
bromperidol	affects response to substance	1
VX-agent	increases expression	1
tetrahydropalmatine	affects binding, decreases activity	1
nemonapride	affects response to substance	1
7-hydroxy-2-N,N-dipropylaminotetralin	affects binding, increases activity	1
benzo(f)quinoline	affects binding	1
epigallocatechin gallate	increases activity, affects binding, decreases reaction, increases abundance	1
UH 232	affects binding, decreases activity	1
eticlopride	decreases activity	1
atractylon	affects binding, increases activity	1
ropinirole	affects binding, increases activity	1
quinelorane	affects binding, increases activity	1
5-methoxy-1-methyl-2-(n-propylamino)tetralin	affects binding, decreases activity	1
CGS 15855A	affects binding, increases activity	1
3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol	affects binding, increases activity	1

ChEMBL screening assays

2636 unique, capped per target: 2064 binding, 517 functional, 54 admet, 1 unclassified

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL670661	Binding	Ratio of binding affinities towards human Dopamine receptor D2 and Dopamine receptor D3 receptors was determined	N-(omega-(4-(2-methoxyphenyl)piperazin-1-yl)alkyl)carboxamides as dopamine D2 and D3 receptor ligands. — J Med Chem
CHEMBL827448	Functional	Dopamine receptor D2/D3 selectivity ratio from in vitro functional assays	Dopamine D3 receptor partial agonists and antagonists as potential drug abuse therapeutic agents. — J Med Chem
CHEMBL3877881	ADMET	Displacement of [3H]N-methylspiperone from human D2 receptor expressed in HEKT cell membranes at 10 uM after 90 mins by microbeta scintillation counting method relative to control	Synthesis and evaluation of C9 alkoxy analogues of (-)-stepholidine as dopamine receptor ligands. — Eur J Med Chem

Cellosaurus cell lines

12 cell lines: 9 spontaneously immortalized cell line, 2 transformed cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_9095	A9 L hD2 S.C. 18	Transformed cell line	Male
CVCL_C0SJ	ACTOne DRD2	Transformed cell line	Female
CVCL_E0YI	Ubigene MDA-MB-231 DRD2 KO	Cancer cell line	Female
CVCL_H421	CHO-K1/D2/Galpha15	Spontaneously immortalized cell line	Female
CVCL_H422	CHO-K1/D2s/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KV07	cAMP Hunter CHO-K1 DRD2L Gi	Spontaneously immortalized cell line	Female
CVCL_KV08	cAMP Hunter CHO-K1 DRD2S Gi	Spontaneously immortalized cell line	Female
CVCL_KW86	PathHunter CHO-K1 DRD2L beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KW87	PathHunter CHO-K1 DRD2S beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_VL22	hD2L-CHO	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

169 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00142259	PHASE4	UNKNOWN	Efficacy and Safety of DBS of the GPi in Patients With Primary Generalized and Segmental Dystonia
NCT00950196	PHASE4	COMPLETED	Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia
NCT00998660	PHASE4	COMPLETED	RECHARGE Sub-Study to the Implantable Systems Performance Registry (ISPR)
NCT02263417	PHASE4	COMPLETED	A Randomized Controlled Trail Comparing Subthalamic and Pallidal Deep Brain Stimulation for Dystonia
NCT00169403	PHASE3	UNKNOWN	Pallidal Stimulation in Patients With Idiopathic Generalised Dystonia
NCT03232320	PHASE3	COMPLETED	Meditoxin® Treatment in Patients With Cervical Dystonia
NCT00001784	PHASE2	COMPLETED	Mexiletine for the Treatment of Focal Dystonia
NCT00105430	PHASE2	COMPLETED	Deep Brain Stimulation for Cervical Dystonia
NCT00106782	PHASE2	COMPLETED	Transcranial Electrical Polarization to Treat Focal Hand Dystonia
NCT00122044	PHASE2	COMPLETED	Childhood Hypertonia of Central Origin: A Trial of Anticholinergic Treatment Effects
NCT00169338	PHASE2	COMPLETED	Pallidal Stimulation in Patients With Post-anoxic and Idiopathic Dystonia
NCT00331669	PHASE2	UNKNOWN	Efficacy and Safety of Deep Brain Stimulation (DBS) of the Pallidal (GPi) in Patients With Tardive Dystonia
NCT02107261	PHASE2	COMPLETED	Incobotulinum Toxin A (Xeomin®) As A Treatment For Focal Task-Specific Dystonia Of The Musician’s Hand
NCT02470325	PHASE2	UNKNOWN	The Effects of Cannabis on Dystonia and Spasticity on Pediatric Patients
NCT05027997	PHASE2	COMPLETED	Exploratory Study of Dipraglurant (ADX48621) for the Treatment of Patients With Blepharospasm
NCT06412653	PHASE2	COMPLETED	Prospective Pilot Trial to Address Feasibility and Safety of Oral Zinc in GNAO1 Associated Disorders
NCT07304089	PHASE2	RECRUITING	A Study to Evaluate the Efficacy, Safety, and Tolerability of VIM0423 in Individuals With Isolated Dystonia
NCT01433757	PHASE1	COMPLETED	Ampicillin for DYT-1 Dystonia Motor Symptoms
NCT01698450	PHASE1	COMPLETED	Magnetic Resonance (MR) Guided Functional Ultrasound-Neurosurgery for Movement Disorders
NCT02982304	PHASE1	UNKNOWN	Multi-Target Pallidal and Thalamic Deep Brain Stimulation for Hemi-Dystonia
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT06554288	PHASE1	RECRUITING	Pharmacogenomic Contributions to Trihexyphenidyl Biotransformation and Response in Children With Dystonic Cerebral Palsy
NCT06999096	Not specified	RECRUITING	Long-read Genome Sequencing for the Molecular Diagnosis of Dystonia
NCT00004421	PHASE2/PHASE3	COMPLETED	Deep Brain Stimulation in Treating Patients With Dystonia
NCT00272246	PHASE2/PHASE3	UNKNOWN	Bilateral Internal Pallidum Stimulation in Primary Generalized Dystonia
NCT00608231	PHASE2/PHASE3	WITHDRAWN	Dexmedetomidine Effects on Microelectrode Recording in Deep Brain Stimulation
NCT04277247	PHASE2/PHASE3	UNKNOWN	Botulinum Toxin Type A for Foot Dystonia-associated Pain in Parkinson’s Disease
NCT02015039	PHASE1/PHASE2	COMPLETED	Pilot Trial of Botulinum Toxin and Occupational Therapy for Writer’s Cramp
NCT02911103	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Deep Brain Stimulation Surgery for Focal Hand Dystonia
NCT04727177	EARLY_PHASE1	UNKNOWN	Precision-targeted Transcranial Magnetic Stimulation in the Treatment of Primary Dystonia
NCT00006336	Not specified	COMPLETED	Sensory Training to Treat Focal Dystonia
NCT00017875	Not specified	COMPLETED	Transcranial Magnetic Stimulation (TMS) Studies of Dystonia
NCT00029601	Not specified	COMPLETED	Surround Inhibition in Patients With Dystonia
NCT00031369	Not specified	TERMINATED	Brain Anatomy in Dystonia
NCT00047957	Not specified	COMPLETED	Brain Inhibition of Muscle Movement in Normal Volunteers
NCT00050024	Not specified	COMPLETED	Transcranial Magnetic Stimulation and Electrical Stimulation of Nerves to Study Focal Dystonia
NCT00072956	Not specified	COMPLETED	The Physiology of Tricks
NCT00082615	Not specified	COMPLETED	Neurophysiological Markers in Patients With Craniofacial Dystonia and Their Relatives
NCT00102999	Not specified	COMPLETED	Brain Function in Focal Dystonia
NCT00285870	Not specified	COMPLETED	Quantification of Upper Extremity Hypertonia