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Protein / target

D(3) dopamine receptor

Encoded byDRD3P35462Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
36
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 DRD3 · Genetic literature evidence · score 0.30

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 that is primarily expressed in limbic areas of the brain and is involved in the modulation of cognitive, emotional, and endocrine functions.

View complete UniProt function annotation

Dopamine receptor that is primarily expressed in limbic areas of the brain and is involved in the modulation of cognitive, emotional, and endocrine functions (PubMed:39984436). Plays a key role in regulating neuronal signaling pathways associated with motivation, reward, and behavior (PubMed:39984436). Coupled to G(i)/G(o) proteins; activation leads to inhibition of adenylate cyclase and decreased intracellular cAMP levels (PubMed:10578130). Involved in the control of locomotor activity and implicated in several neuropsychiatric disorders, including schizophrenia and substance use disorders (PubMed:39984436). Promotes cell proliferation through MAP kinase signaling (PubMed:19520868). Also involved in autophagy regulation: receptor activation stimulates AMPK, which phosphorylates RPTOR and enhances its interaction with MTOR, thereby inhibiting MTORC1 signaling and its downstream target RPS6KB1. This leads to activation of ULK1 and initiation of the autophagy cascade (PubMed:31538542). Forms heterotetramers with DRD1 to potentiate beta-arrestin recruitment and mediate locomotor activity (By similarity)

Subcellular location

Cell membrane
Domains and Gene Ontology detail (38)

Gene Ontology

  • Cplasma membrane
  • Csynapse
  • Fdopamine neurotransmitter receptor activity, coupled via Gi/Go
  • FG protein-coupled receptor activity
  • Pacid secretion
  • Padenylate cyclase-activating dopamine receptor signaling pathway
  • Padenylate cyclase-inhibiting dopamine receptor signaling pathway
  • Parachidonate secretion
  • Pbehavioral response to cocaine
  • Pcircadian regulation of gene expression
  • Pdopamine metabolic process
  • PG protein-coupled receptor internalization

400 aa · 44 kDa · 2 isoforms

Biological roles

Reactome v97

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

Excitatory neurotransmissionGOMotor controlUniProt · GOG protein-coupled signallingGO
View supporting evidence

Excitatory neurotransmission

  • ·negative regulation of synaptic transmission, glutamatergic

Motor control

  • ·Dopamine receptor that is primarily expressed in limbic areas of the brain and is involv…
  • ·locomotory behavior

G protein-coupled signalling

  • ·G protein-coupled receptor activity
  • ·G protein-coupled receptor internalization
  • ·G protein-coupled receptor signaling pathway
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.

GNB1GNAI1DRD4GNG2GNB3GNB2BDNFGNG7DRD1SLC6A4DRD3

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

4 medicines · 8 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
Parkinson's Disease1 medicine
Tourette's Syndrome1 medicine

36 medicines meet Open Targets' target-level approved-medicine definition; the 4 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

4

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.

Levodopa
Narrow target profileApprovedAgonist

Dopamine D3 receptor agonist

Indicated for Parkinson's Disease

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 DRD2, 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 DRD2, 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 DRD2, 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 DRD3

Gene-level evidence surfaced through the gene DRD3that 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
0.86Well supported

Clinical evidence dominant · Open Targets 0.67

Parkinson's Disease
0.78Well supported

Clinical evidence dominant · Open Targets 0.63

Major depressive disorder
0.76Well 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
0.86
agreement 0.760.96
Clinical59%Genetic literature19%Animal model17%Literature6%Geneticdup

Open Targets aggregate 0.67 · 4 independent evidence families · 1 not counted as duplicate

Parkinson's DiseaseWell supported
0.78
agreement 0.620.93
Clinical86%Literature14%

Open Targets aggregate 0.63 · 2 independent evidence families

Major depressive disorderWell supported
0.76
agreement 0.600.91
Clinical90%Literature11%

Open Targets aggregate 0.61 · 2 independent evidence families

Bipolar DisorderWell supported
0.75
agreement 0.600.91
Clinical97%Literature3%

Open Targets aggregate 0.61 · 2 independent evidence families

Restless Legs SyndromeModerately supported
0.74
agreement 0.580.90
Clinical98%Literature2%

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
Schizophrenia0.67
Parkinson's Disease0.63
Major depressive disorder0.61
Bipolar Disorder0.61
Restless Legs Syndrome0.60
Psychotic disorder0.60
bipolar I disorder0.59
Depressive Disorder0.55
Tourette's Syndrome0.54

Drug development

45 compounds recorded · 36 approved · 8 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 4 drugs that target this protein in Forefront's canonical graph (4 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
AMOXAPINEApproval
TRIFLUOPERAZINE HYDROCHLORIDEApproval
LOXAPINE SUCCINATEApproval
THIORIDAZINEApproval
PIMOZIDEApproval
CHLORPROMAZINEApproval
ETILEVODOPAPhase 3
PERGOLIDE MESYLATEUnknown
TRAZPIROBENPhase 2
ROPINIROLEApproval

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 (10)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Med-Quality PocketSM · 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

adverse eventsClinPGxcognitive impairmentClinPGxinsomniaBrennan et al. (2024)nauseaBrennan et al. (2024)role in facilitating drug addiction/dependenceBrennan et al. (2024)extrapyramidal symptomsClinPGxSevere akathisiaBrennan et al. (2024)opioid dependenceClinPGxFacilitate reward reinforcementBrennan et al. (2024)

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

COMPLETED · via Levodopa · NCT02744391

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 3 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. Label change2026-07-07

    Label change: LEVODOPA (NDA209184)

    fda · regulatory · fda · via Levodopa

  4. Label change2026-06-24

    Label change: CARBIDOPA AND LEVODOPA (ANDA216505)

    fda · regulatory · fda · via Levodopa

  5. Regulatory approval2026-06-04

    Approval: HALOPERIDOL (ANDA214470)

    fda · regulatory · fda · via haloperidol

  6. Label change2026-03-31

    Label change: LEVODOPA (NDA209184)

    fda · regulatory · fda · via Levodopa

  7. Label change2026-02-09

    Label change: OLANZAPINE (ANDA076133)

    fda · regulatory · fda · via olanzapine

  8. New publication2025-06-09
    The role of L-DOPA in neurological and neurodegenerative complications: a review.

    Molecular and cellular biochemistry · 2025 · 2 citations · Europe PMC · via Levodopa

  9. New publication2024-04-03
    The Gut Microbiota in Parkinson Disease: Interactions with Drugs and Potential for Therapeutic Applications.

    CNS drugs · 2024 · 27 citations · Europe PMC · via Levodopa

  10. New publication2023-12-01
    Hippocampal synaptic failure is an early event in experimental parkinsonism with subtle cognitive deficit.

    Brain : a journal of neurology · 2023 · 19 citations · Europe PMC · via Levodopa

  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 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.