Back to discover

Protein / target

D(2) dopamine receptor

Encoded byDRD2P14416Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
91
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Dopamine neurotransmitter receptor activity, coupled via Gi/Go

Strongest disease association

Major depressive disorder

Via encoding gene DRD2 · Genetic evidence · score 0.82

Therapeutic position

Established drug target

Small molecules

Research activity

Emerging research

4 papers · latest 2024

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.

View complete UniProt function annotation

Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase (PubMed:21645528, PubMed:39103320). Positively regulates postnatal regression of retinal hyaloid vessels via suppression of VEGFR2/KDR activity, downstream of OPN5 (By similarity)

Subcellular location

Cell membraneGolgi apparatus membrane
Domains and Gene Ontology detail (119)

Gene Ontology

  • Cacrosomal vesicle
  • Caxon
  • Caxon terminus
  • Cciliary membrane
  • Ccilium
  • Cdendrite
  • Cdendritic spine
  • Cdopaminergic synapse
  • Cendocytic vesicle
  • CG protein-coupled receptor complex
  • CGABA-ergic synapse
  • Cglutamatergic synapse

443 aa · 51 kDa · 3 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Inhibitory neurotransmissionGOExcitatory neurotransmissionGOCell proliferation & survivalGOCell migrationGOG protein-coupled signallingGOImmune signallingGO
View supporting evidence

Inhibitory neurotransmission

  • ·GABA-ergic synapse
  • ·cerebral cortex GABAergic interneuron migration
  • ·regulation of synaptic transmission, GABAergic

Excitatory neurotransmission

  • ·glutamatergic synapse
  • ·excitatory postsynaptic potential
  • ·negative regulation of synaptic transmission, glutamatergic

Cell proliferation & survival

  • ·negative regulation of cell population proliferation

Cell migration

  • ·negative regulation of cell migration

G protein-coupled signalling

  • ·G protein-coupled receptor complex
  • ·G protein-coupled receptor activity
  • ·G protein-coupled receptor internalization
  • ·phospholipase C-activating G protein-coupled receptor signaling pathway

Immune signalling

  • ·negative regulation of innate immune response
  • ·positive regulation of cytokinesis
View underlying pathways (1)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

SLC6A3GNAI1ARRB2ADORA2AGNB1CNR1GNAI2NCS1GNG2ARRB1DRD2

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Approved medicines with mapped indications

12 medicines · 11 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Psychomotor Agitation3 medicines
Autistic Disorder2 medicines
Mental Disorders2 medicines
Tourette's Syndrome2 medicines
Conduct Disorder1 medicine
Depressive Disorder1 medicine
Digestive System Diseases1 medicine
Postoperative Nausea and Vomiting1 medicine

91 medicines meet Open Targets' target-level approved-medicine definition; the 12 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

13

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

Risperidone
Narrow target profileApprovedAntagonist

Dopamine D2 receptor antagonist

Indicated for Autistic Disorder, Bipolar Disorder, Psychotic Disorders, Schizophrenia

Direct interaction with this protein · 1 of 3 recorded protein targets — narrow recorded profile

Perphenazine
Narrow target profileApprovedAntagonist

Dopamine D2 receptor antagonist

Indicated for Postoperative Nausea and Vomiting, Psychotic Disorders, Schizophrenia

Direct interaction with this protein · Only this protein recorded as a target

Quetiapine Fumarate
Narrow target profileApprovedAntagonist

Dopamine D2 receptor antagonist

Indicated for Bipolar Disorder, Schizophrenia

Direct interaction with this protein · 1 of 3 recorded protein targets — narrow recorded profile

Clozapine
Narrow target profileApprovedAntagonist

Dopamine D2 receptor antagonist

Indicated for Psychotic Disorders, Schizophrenia

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

paliperidone palmitate
Narrow target profileApprovedAntagonist

Dopamine D2 receptor antagonist

Indicated for Psychotic Disorders, Schizophrenia

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

aripiprazole
Narrow target profileApprovedPartial agonist

Dopamine D2 receptor partial agonist

Indicated for Autistic Disorder, Bipolar Disorder, Depressive Disorder, Psychomotor Agitation

Direct interaction with this protein · 1 of 3 recorded protein targets — narrow recorded profile

View all 13 targeting drugs
domperidone
Narrow target profileApprovedAntagonist

Dopamine D2 receptor antagonist

Indicated for Digestive System Diseases

Direct interaction with this protein · Only this protein recorded as a target

paliperidone
Narrow target profileApprovedAntagonist

Dopamine D2 receptor antagonist

Indicated for Psychotic Disorders, Schizophrenia

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

brexpiprazole
Narrow target profileApprovedPartial agonist

Dopamine D2 receptor partial agonist

Indicated for Psychotic Disorders, Schizophrenia

Direct interaction with this protein · 1 of 3 recorded protein targets — narrow recorded profile

pridopidine
Narrow target profilePhase 3Modulator

Dopamine D2 receptor modulator

Direct interaction with this protein · Only this protein recorded as a target

olanzapine
ApprovedAntagonist

D2-like dopamine receptor antagonist

Indicated for Bipolar Disorder, Mental Disorders, Psychomotor Agitation, Psychotic Disorders

Acts on a complex — shared with DRD3, DRD4 · 1 of 5 recorded protein targets

haloperidol
ApprovedInverse agonist

D2-like dopamine receptor inverse agonist

Indicated for Conduct Disorder, Psychotic Disorders, Schizophrenia, Tourette's Syndrome

Acts on a complex — shared with DRD3, DRD4 · 1 of 4 recorded protein targets

loxapine
ApprovedAntagonist

D2-like dopamine receptor antagonist

Indicated for Bipolar Disorder, Mental Disorders, Psychomotor Agitation, Psychotic Disorders

Acts on a complex — shared with DRD3, DRD4 · 1 of 5 recorded protein targets

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene DRD2

Gene-level evidence surfaced through the gene DRD2that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Major depressive disorder
0.96Well supported

Genetic evidence dominant · Open Targets 0.74

Schizophrenia
0.93Well supported

Clinical evidence dominant · Open Targets 0.73

Bipolar Disorder
0.92Well supported

Clinical evidence dominant · Open Targets 0.71

Depressive Disorder
0.87Well supported

Clinical evidence dominant · Open Targets 0.66

Autism Spectrum Disorder
0.86Well supported

Clinical evidence dominant · Open Targets 0.63

View evidence synthesis (5)
Major depressive disorderWell supported
0.96
agreement 0.851.00
Genetic49%Clinical45%Literature5%

Open Targets aggregate 0.74 · 3 independent evidence families

SchizophreniaWell supported
0.93
agreement 0.831.00
Clinical44%Genetic34%Animal model14%Literature8%

Open Targets aggregate 0.73 · 4 independent evidence families

Bipolar DisorderWell supported
0.92
agreement 0.811.00
Clinical52%Genetic46%Literature2%

Open Targets aggregate 0.71 · 3 independent evidence families

Depressive DisorderWell supported
0.87
agreement 0.760.97
Clinical55%Genetic40%Literature5%

Open Targets aggregate 0.66 · 3 independent evidence families

Autism Spectrum DisorderWell supported
0.86
agreement 0.760.97
Clinical52%Genetic47%Literature2%

Open Targets aggregate 0.63 · 3 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Major depressive disorder0.74
Schizophrenia0.73
Bipolar Disorder0.71
Depressive Disorder0.66
Tourette's Syndrome0.65
Parkinson's Disease0.63
Autistic Disorder0.63
Autism Spectrum Disorder0.63
Psychotic disorder0.62
Mental Disorders0.61

Drug development

111 compounds recorded · 91 approved · 16 in clinical development · 4 earlier-stage

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 13 drugs that target this protein in Forefront's canonical graph (12 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
SUMANIROLEPhase 3
FLUPHENAZINE HYDROCHLORIDEApproval
ERGOLOID MESYLATESApproval
BENPERIDOLApproval
ROTIGOTINEApproval
MOLINDONEApproval
PALIPERIDONE PALMITATEApproval
ASENAPINEApproval
QUINAGOLIDEApproval
AMOXAPINEApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (small molecule binder) — no clinical-stage drug of this modality recorded.

Other modalitiesStrong

Approved Drug support this modality.

View underlying tractability evidence (9)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Small Molecule BinderOC · Approved Drug

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

faintingLynch et al. (2017)decreased body temperatureLynch et al. (2017)vomitingLynch et al. (2017)emesisBowes et al. (2012)decreased pituitary hormone secretionLynch et al. (2017)death from cocaine intoxicationClinPGxdrowsinessBowes et al. (2012)orthostatic hypotensionLynch et al. (2017)side effectsClinPGxstereotypyLynch et al. (2017)confusionLynch et al. (2017)confusionBowes et al. (2012)

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

NOT_YET_RECRUITING · via Risperidone · NCT07503002

RECRUITING · via domperidone · NCT04699591

WITHDRAWN · via aripiprazole · NCT05554627

UNKNOWN · via domperidone · NCT02264587

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 8 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Label change2026-08-10

    Label change: OLANZAPINE (ANDA076133)

    fda · regulatory · fda · via olanzapine

  2. Label change2026-08-10

    Label change: OLANZAPINE (ANDA076255)

    fda · regulatory · fda · via olanzapine

  3. Safety communication2026-07-21

    Drug Safety Update: Domperidone: new contraindication in patients with phaeochromocytoma due to the risk of severe hypertension

    mhra · safety · mhra · via domperidone

  4. Label change2026-07-01

    Label change: RISPERIDONE (ANDA076996)

    fda · regulatory · fda · via Risperidone

  5. Regulatory approval2026-06-04

    Approval: HALOPERIDOL (ANDA214470)

    fda · regulatory · fda · via haloperidol

  6. Product recall2026-05-27

    Recall (Class II): ARIPIPRAZOLE

    fda · safety · fda · via aripiprazole

  7. New publication2024-08-26
    Long-Acting Injectable Antipsychotic Initiation in Child and Adolescent Patients with Psychiatric Disorders.

    Journal of child and adolescent psychopharmacology · 2025 · 4 citations · Europe PMC · via paliperidone palmitate

  8. New publication2024-06-08
    Effects of PDE10A inhibitor MK-8189 in people with an acute episode of schizophrenia: A randomized proof-of-concept clinical trial.

    Schizophrenia research · 2024 · 13 citations · Europe PMC · via Risperidone

  9. Safety communication2023-12-18

    Drug Safety Update: Aripiprazole (Abilify and generic brands): risk of pathological gambling

    mhra · safety · mhra · via aripiprazole

  10. New publication2023-10-01
    Real-world effectiveness of pharmacological treatments for bipolar disorder: register-based national cohort study.

    The British journal of psychiatry : the journal of mental science · 2023 · 24 citations · Europe PMC · via Clozapine

  11. Safety communication2021-12-10

    Drug Safety Update: Haloperidol (Haldol): reminder of risks when used in elderly patients for the acute treatment of delirium

    mhra · safety · mhra · via haloperidol

  12. New publication2005-09-19
    Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.

    The New England journal of medicine · 2005 · 3,569 citations · Europe PMC · via Perphenazine

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.

Research activity

4 papers · to 2024

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Recent

Europe PMC papers linked directly to this protein.

Related family literature

2

Papers about “Receptors, Dopamine” — a broader family this protein belongs to. Shown as context; not counted as papers specifically about this protein.

The effects of social isolation stress and discrimination on mental health.

Brandt L · Translational psychiatry · 2022

via Receptors, Dopamine

Molecular pathology of schizophrenia: more than one disease process?

Crow TJ · British medical journal · 1980

via Receptors, Dopamine

Europe PMC literature, reached through curated HGNC family membership. Membership is a taxonomic relationship — it does not imply this protein participates in every mechanism these papers discuss.