Protein / target

D(4) dopamine receptor

DRD4P21917Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
30
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

schizophrenia

Clinical evidence · score 0.63

Therapeutic maturity

Clinically validated target

30 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

30 approved · 2 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 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.

Synaptic signallingGOG protein-coupled signallingGOInhibitory neurotransmissionGOExcitatory neurotransmissionGOMetabolic enzyme activityGOMotor controlGO
View supporting evidence

Synaptic signalling

  • ·glutamatergic synapse
  • ·postsynapse
  • ·dopamine neurotransmitter receptor activity
  • ·dopamine neurotransmitter receptor activity, coupled via Gi/Go

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…

Inhibitory neurotransmission

  • ·inhibitory postsynaptic potential

Excitatory neurotransmission

  • ·glutamatergic synapse

Metabolic enzyme activity

  • ·regulation of dopamine metabolic process

Motor control

  • ·adult locomotory behavior
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.

Drugs targeting this protein

1

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.

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 DRD2, DRD3 · 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.

Highest-confidence therapeutic associations

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

schizophrenia1.00

Clinical · overall 0.63

bipolar disorder1.00

Clinical · overall 0.61

Parkinson disease0.99

Clinical · overall 0.61

restless legs syndrome0.98

Clinical · overall 0.60

Agitation0.98

Clinical · overall 0.60

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

major depressive disorder0.61

Clinical

psychotic disorder0.59

Clinical

bipolar I disorder0.59

Clinical

depressive disorder0.55

Clinical

hypogonadism0.54

Clinical

Show all associations
schizophrenia0.63
Parkinson disease0.61
bipolar disorder0.61
major depressive disorder0.61
restless legs syndrome0.60
Agitation0.60
psychotic disorder0.59
bipolar I disorder0.59
depressive disorder0.55
hypogonadism0.54

Open Targets ranks 524 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 · 33 total

TRIFLUOPERAZINE HYDROCHLORIDEApproval

schizophrenia · anxiety disorder · mental disorder

LEVOMEPROMAZINEApproval

bipolar disorder · psychotic disorder · psychotic disorder

SARIZOTANPhase 3

Parkinson disease · movement disorder · Rett syndrome

THIORIDAZINEApproval

schizophrenia · psychotic disorder · acute myeloid leukemia

AMOXAPINEApproval

major depressive disorder

PERGOLIDE MESYLATEUnknown
DROPERIDOLApproval

Nausea and vomiting · Nausea · psychotic disorder

LOXAPINEApproval

bipolar I disorder · schizophrenia · Agitation

LOXAPINE SUCCINATEApproval

schizophrenia

APOMORPHINEApproval

Parkinson disease · erectile dysfunction · epilepsy

Tractability

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

Safety liabilities

receptor binding

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 olanzapine · NCT00057408

COMPLETED · via olanzapine · NCT00685334

ClinicalTrials.gov via the drug-target graph.

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.

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.

schizophreniaWell supported
0.82
agreement 0.690.95
Clinical71%Animal model22%Literature7%

Open Targets aggregate 0.63 · 3 independent evidence families

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

What's happening now

16

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

  1. Withdrawn from market2025-08-12

    Market withdrawal: Olanzapine Apotex (EMA)

    ema · market · ema · via olanzapine

  2. 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

  3. 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

  4. 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

  5. New publication2017-08-30
    Olanzapine for prevention of chemotherapy-induced nausea and vomiting in children and adolescents: a multi-center, feasibility study.

    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2018 · 17 citations · Europe PMC · via olanzapine

  6. Regulatory approval2009-12-11

    Approval: Olazax (EMA)

    ema · regulatory · ema · via olanzapine

  7. Regulatory approval2009-12-10

    Approval: Olazax Disperzi (EMA)

    ema · regulatory · ema · via olanzapine

  8. Regulatory approval2009-12-03

    Approval: Olanzapine Glenmark (EMA)

    ema · regulatory · ema · via olanzapine

  9. Regulatory approval2009-12-03

    Approval: Olanzapine Glenmark Europe (EMA)

    ema · regulatory · ema · via olanzapine

  10. Regulatory approval2008-11-19

    Approval: Zypadhera (EMA)

    ema · regulatory · ema · via olanzapine

  11. Regulatory approval2008-10-06

    Approval: Olanzapine Viatris (previously Olanzapine Mylan) (EMA)

    ema · regulatory · ema · via olanzapine

  12. Regulatory approval2007-12-12

    Approval: Olanzapine Teva (EMA)

    ema · regulatory · ema · 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.