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Protein / target

D(4) dopamine receptor

Encoded byDRD4P21917Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
30
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

Schizophrenia

Via encoding gene DRD4 · Clinical evidence · score 0.63

Therapeutic position

Established drug target

Small molecules

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 responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior.

View complete UniProt function annotation

Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Activated by dopamine, but also by epinephrine and norepinephrine, and by numerous synthetic agonists and drugs (PubMed:16423344, PubMed:27659709, PubMed:29051383, PubMed:9003072). Agonist binding triggers signaling via G proteins that inhibit adenylyl cyclase (PubMed:16423344, PubMed:27659709, PubMed:29051383, PubMed:7512953, PubMed:7643093). Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity)

Subcellular location

Cell membrane
Domains and Gene Ontology detail (39)

Gene Ontology

  • Cdendrite
  • Cglutamatergic synapse
  • Cmembrane
  • Cplasma membrane
  • Cpostsynapse
  • Fdopamine binding
  • Fdopamine neurotransmitter receptor activity
  • Fdopamine neurotransmitter receptor activity, coupled via Gi/Go
  • Fepinephrine binding
  • FG protein-coupled serotonin receptor activity
  • Fidentical protein binding
  • Fmetal ion binding

419 aa · 44 kDa

Biological roles

Reactome v97

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

Inhibitory neurotransmissionGOG protein-coupled signallingGO
View supporting evidence

Inhibitory neurotransmission

  • ·inhibitory postsynaptic potential

G protein-coupled signalling

  • ·G protein-coupled serotonin receptor activity
  • ·adenylate cyclase-modulating G protein-coupled receptor signaling pathway
  • ·G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messen…
View underlying pathways (2)

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.

SLC6A4SLC6A3DRD3COMTMAOAGNB3KLHL12BDNFDRD2GNAI1DRD4

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

3 medicines · 7 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.

Psychotic Disorders3 medicines
Schizophrenia3 medicines
Bipolar Disorder2 medicines
Mental Disorders2 medicines
Psychomotor Agitation2 medicines
Conduct Disorder1 medicine
Tourette's Syndrome1 medicine

30 medicines meet Open Targets' target-level approved-medicine definition; the 3 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

3

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.

olanzapine
ApprovedAntagonist

D2-like dopamine receptor antagonist

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

Acts on a complex — shared with DRD2, DRD3 · 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 DRD2, DRD3 · 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 DRD2, DRD3 · 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 DRD4

Gene-level evidence surfaced through the gene DRD4that 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.

Schizophrenia
0.82Well supported

Clinical evidence dominant · Open Targets 0.63

Parkinson's Disease
0.76Well supported

Clinical evidence dominant · Open Targets 0.61

Major depressive disorder
0.75Well supported

Clinical evidence dominant · Open Targets 0.61

Bipolar Disorder
0.75Well supported

Clinical evidence dominant · Open Targets 0.61

Restless Legs Syndrome
0.74Moderately supported

Clinical evidence dominant · Open Targets 0.60

View evidence synthesis (5)
SchizophreniaWell supported
0.82
agreement 0.690.95
Clinical71%Animal model22%Literature7%

Open Targets aggregate 0.63 · 3 independent evidence families

Parkinson's DiseaseWell supported
0.76
agreement 0.600.91
Clinical94%Literature6%

Open Targets aggregate 0.61 · 2 independent evidence families

Major depressive disorderWell supported
0.75
agreement 0.600.91
Clinical90%Literature10%

Open Targets aggregate 0.61 · 2 independent evidence families

Bipolar DisorderWell supported
0.75
agreement 0.600.91
Clinical96%Literature4%

Open Targets aggregate 0.61 · 2 independent evidence families

Restless Legs SyndromeModerately supported
0.74
agreement 0.580.89
Clinical100%Literature1%

Open Targets aggregate 0.60 · 2 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
Schizophrenia0.63
Parkinson's Disease0.61
Bipolar Disorder0.61
Major depressive disorder0.61
Restless Legs Syndrome0.60
Psychotic disorder0.59
Depressive Disorder0.55

Drug development

33 compounds recorded · 30 approved · 2 in clinical development · 1 earlier-stage

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 3 drugs that target this protein in Forefront's canonical graph (3 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
TRIFLUOPERAZINE HYDROCHLORIDEApproval
LEVOMEPROMAZINEApproval
SARIZOTANPhase 3
THIORIDAZINEApproval
AMOXAPINEApproval
PERGOLIDE MESYLATEUnknown
DROPERIDOLApproval
LOXAPINEApproval
LOXAPINE SUCCINATEApproval
APOMORPHINEApproval

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 (uniprot ubiquitination and small molecule binder) — no clinical-stage drug of this modality recorded.

Other modalitiesStrong

Approved Drug support this modality.

View underlying tractability evidence (10)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · UniProt UbiquitinationPR · Small Molecule BinderOC · Approved Drug

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

receptor bindingToxCast

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)

ACTIVE_NOT_RECRUITING · via haloperidol · NCT03021486

COMPLETED · via olanzapine · NCT06357104

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 2 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. Regulatory approval2026-06-04

    Approval: HALOPERIDOL (ANDA214470)

    fda · regulatory · fda · via haloperidol

  4. Label change2026-02-09

    Label change: OLANZAPINE (ANDA076133)

    fda · regulatory · fda · via olanzapine

  5. Label change2026-02-09

    Label change: OLANZAPINE (ANDA076255)

    fda · regulatory · fda · via olanzapine

  6. Withdrawn from market2025-08-12

    Market withdrawal: Olanzapine Apotex (EMA)

    ema · market · ema · via olanzapine

  7. Label change2023-02-10

    Label change: OLANZAPINE (ANDA076255)

    fda · regulatory · fda · via olanzapine

  8. 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

  9. New publication2020-06-01
    Olanzapine for the Prevention of Postdischarge Nausea and Vomiting after Ambulatory Surgery: A Randomized Controlled Trial.

    Anesthesiology · 2020 · 18 citations · Europe PMC · via olanzapine

  10. New publication2019-03-08
    Mitigation of Olanzapine-Induced Weight Gain With Samidorphan, an Opioid Antagonist: A Randomized Double-Blind Phase 2 Study in Patients With Schizophrenia.

    The American journal of psychiatry · 2019 · 57 citations · Europe PMC · via olanzapine

  11. New publication2018-03-14
    Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder.

    Bipolar disorders · 2018 · 1,126 citations · Europe PMC · via olanzapine

  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 olanzapine

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.

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.

Related literature

1

Papers indexed under “Receptors, Dopamine D4” — a subject heading that covers this protein without being specific to it. Shown as context; not counted as this protein's own research activity.

Genetics of child aggression, a systematic review.

Koyama E · Translational psychiatry · 2024

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