Protein / target
D(3) dopamine receptor
Protein at a glance
Biological role
Dopamine neurotransmitter receptor activity, coupled via Gi/Go
Primary system
Nervous system
Strongest disease association
schizophrenia
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
36 approved · 8 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
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
Domains and Gene Ontology detail (38)Hide
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
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Motor control
- ·Dopamine receptor that is primarily expressed in limbic areas of the brain and is involv…
- ·locomotory behavior
Synaptic signalling
- ·synapse
- ·dopamine neurotransmitter receptor activity, coupled via Gi/Go
- ·negative regulation of synaptic transmission, glutamatergic
- ·regulation of dopamine uptake involved in synaptic transmission
G protein-coupled signalling
- ·G protein-coupled receptor activity
- ·G protein-coupled receptor internalization
- ·G protein-coupled receptor signaling pathway
Excitatory neurotransmission
- ·negative regulation of synaptic transmission, glutamatergic
Kinase signalling
- ·negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
Immune signalling
- ·positive regulation of cytokinesis
View underlying pathways (2)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
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.
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
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.
Dopamine D3 receptor agonist
Appears in clinical studies involving Parkinson disease, Parkinson disease, injury, restless legs syndrome
D2-like dopamine receptor antagonist
Appears in clinical studies involving bipolar disorder, schizophrenia, major depressive disorder, Agitation
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
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.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 324 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 · 45 total
major depressive disorder
schizophrenia · anxiety disorder · mental disorder
schizophrenia
schizophrenia · psychotic disorder · acute myeloid leukemia
Tics · Tourette syndrome · schizophrenia
Nausea and vomiting · schizophrenia · porphyria
Parkinson disease
gastroparesis · diabetes mellitus · Abnormality of the gastrointestinal tract
Parkinson disease · restless legs syndrome · Parkinson disease
Tractability
Safety liabilities
Clinical trials
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)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
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.
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
Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- Label change
Label change: LEVODOPA (NDA209184)
- Label change
Label change: CARBIDOPA AND LEVODOPA (ANDA216505)
- Label change
Label change: LEVODOPA (NDA209184)
- Withdrawn from market
Market withdrawal: Olanzapine Apotex (EMA)
- New publicationThe role of L-DOPA in neurological and neurodegenerative complications: a review.
- New publicationThe Gut Microbiota in Parkinson Disease: Interactions with Drugs and Potential for Therapeutic Applications.
- New publicationHippocampal synaptic failure is an early event in experimental parkinsonism with subtle cognitive deficit.
- Regulatory approval
Approval: CARBIDOPA AND LEVODOPA (ANDA216505)
- New publicationOral berberine improves brain dopa/dopamine levels to ameliorate Parkinson's disease by regulating gut microbiota.
- Label change
Label change: LEVODOPA (NDA209184)
- Label change
Label change: LEVODOPA (NDA209184)
- New publicationOlanzapine for the Prevention of Postdischarge Nausea and Vomiting after Ambulatory Surgery: A Randomized Controlled Trial.
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.