Protein / target

D(2) dopamine receptor

DRD2P14416Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
91
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Dopamine neurotransmitter receptor activity, coupled via Gi/Go

Primary system

Nervous system

Strongest disease association

major depressive disorder

Genetic evidence · score 0.82

Therapeutic maturity

Clinically validated target

91 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

91 approved · 16 in clinical development

30 linked trials

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

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.

Synaptic signallingGOG protein-coupled signallingGOInhibitory neurotransmissionGOExcitatory neurotransmissionGOKinase signallingGOImmune signallingGO
View supporting evidence

Synaptic signalling

  • ·dopaminergic synapse
  • ·GABA-ergic synapse
  • ·glutamatergic synapse
  • ·postsynaptic membrane

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

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

Kinase signalling

  • ·negative regulation of dephosphorylation
  • ·negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction

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.

Drugs targeting this protein

7

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

Risperidone
Narrow target profileApprovedAntagonist

Dopamine D2 receptor antagonist

Appears in clinical studies involving bipolar disorder, schizophrenia, aggressive behavior, autism

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

Perphenazine
Narrow target profileApprovedAntagonist

Dopamine D2 receptor antagonist

Appears in clinical studies involving schizophrenia, Nausea and vomiting, psychotic disorder, Agitation

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

Quetiapine Fumarate
Narrow target profileApprovedAntagonist

Dopamine D2 receptor antagonist

Appears in clinical studies involving schizophrenia, bipolar disorder, bipolar I disorder, major depressive disorder

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

Clozapine
Narrow target profileApprovedAntagonist

Dopamine D2 receptor antagonist

Appears in clinical studies involving schizophrenia, schizoaffective disorder, psychotic disorder, bipolar disorder

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

paliperidone palmitate
Narrow target profileApprovedAntagonist

Dopamine D2 receptor antagonist

Appears in clinical studies involving schizophrenia, schizoaffective disorder, psychotic symptoms, bipolar I disorder

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

aripiprazole
Narrow target profileApprovedPartial agonist

Dopamine D2 receptor partial agonist

Appears in clinical studies involving schizophrenia, major depressive disorder, bipolar disorder, Agitation

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

olanzapine
ApprovedAntagonist

D2-like dopamine receptor antagonist

Appears in clinical studies involving bipolar disorder, schizophrenia, major depressive disorder, Agitation

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

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

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

major depressive disorder0.82

Genetic · overall 0.74

bipolar disorder0.66

Genetic · overall 0.71

autism spectrum disorder0.59

Genetic · overall 0.63

schizophrenia0.57

Genetic · overall 0.73

mental disorder0.56

Genetic · overall 0.61

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

autism1.00

Clinical · overall 0.63

Parkinson disease1.00

Clinical · overall 0.63

psychotic disorder0.99

Clinical · overall 0.62

Tourette syndrome0.95

Clinical · overall 0.65

depressive disorder0.94

Clinical · overall 0.66

Show all associations
major depressive disorder0.74
schizophrenia0.73
bipolar disorder0.71
depressive disorder0.66
Tourette syndrome0.65
Parkinson disease0.63
autism0.63
autism spectrum disorder0.63
psychotic disorder0.62
mental disorder0.61

Open Targets ranks 1,797 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 111 total

SUMANIROLEPhase 3

Parkinson disease · Parkinson disease

FLUPHENAZINE HYDROCHLORIDEApproval

mental disorder · plasma cell myeloma

ERGOLOID MESYLATESApproval

cardiovascular disorder · vascular dementia · fragile X syndrome

BENPERIDOLApproval

schizophrenia · psychotic disorder

ROTIGOTINEApproval

Parkinson disease · Parkinson disease · restless legs syndrome

MOLINDONEApproval

schizophrenia · psychotic disorder · attention deficit-hyperactivity disorder

PALIPERIDONE PALMITATEApproval

schizophrenia · schizoaffective disorder · psychotic symptoms

ASENAPINEApproval

bipolar I disorder · schizophrenia · bipolar disorder

QUINAGOLIDEApproval

hyperprolactinemia · Increased circulating prolactin concentration · adenomyosis

AMOXAPINEApproval

major depressive disorder

Tractability

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

Safety liabilities

faintingdecreased body temperaturevomitingemesisdecreased pituitary hormone secretiondeath from cocaine intoxicationdrowsinessorthostatic hypotensionside effectsstereotypyconfusionconfusion

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.

Show remaining trials (24)

COMPLETED · via Risperidone · NCT04587115

COMPLETED · via Risperidone · NCT00073658

ClinicalTrials.gov via the drug-target graph.

Related literature

4

Papers indexed under “Receptors, Dopamine D2” — a subject heading that covers this protein without being specific to it. Shown as context; not counted as this protein's own research activity.

Europe PMC literature, reached through a MeSH descriptor linked to this protein.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

60

Recent activity around this target, drawn from one canonical event stream. Every item is reached through 6 drugs that target this protein, so each event is news about that drug rather than about the protein directly.

  1. Label change2026-07-01

    Label change: RISPERIDONE (ANDA076996)

    fda · regulatory · fda · via Risperidone

  2. Label change2026-06-08

    Label change: RISPERIDONE (ANDA077494)

    fda · regulatory · fda · via Risperidone

  3. Product recall2026-05-27

    Recall (Class II): ARIPIPRAZOLE

    fda · safety · fda · via aripiprazole

  4. Label change2025-11-04

    Label change: RISPERIDONE (ANDA091384)

    fda · regulatory · fda · via Risperidone

  5. Withdrawn from market2025-08-12

    Market withdrawal: Olanzapine Apotex (EMA)

    ema · market · ema · via olanzapine

  6. Label change2025-06-17

    Label change: RISPERIDONE (ANDA079088)

    fda · regulatory · fda · via Risperidone

  7. Label change2025-01-22

    Label change: RISPERIDONE (ANDA076996)

    fda · regulatory · fda · via Risperidone

  8. Label change2025-01-14

    Label change: RISPERIDONE (ANDA076996)

    fda · regulatory · fda · via Risperidone

  9. Label change2024-09-09

    Label change: RISPERIDONE (ANDA091384)

    fda · regulatory · fda · via Risperidone

  10. 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

  11. Label change2024-06-12

    Label change: RISPERIDONE (ANDA079088)

    fda · regulatory · fda · via Risperidone

  12. Label change2024-06-12

    Label change: RISPERIDONE (ANDA079088)

    fda · regulatory · fda · via Risperidone

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.