DRD3 dopamine receptor D3
ENSG00000151577 · protein coding · Open Targets profile
G protein-coupled receptor for dopamine, a catecholamine neurotransmitter hormone that functions as the brain's 'reward chemical', driving motivation, reinforcement learning and pleasure (PubMed:19520868, PubMed:33548201, PubMed:37221270, PubMed:39237617, PubMed:39984436, PubMed:8301582). Dopamine binding causes a conformation change that triggers signaling via guanine nucleotide- binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:10578130, PubMed:33548201, PubMed:37221270, PubMed:39237617). Dopamine receptors can be classified in two categories: (1) DRD3 (together with DRD2 and DRD4) is a D2-type receptor and is coupled to G(i)/G(o) G proteins, mediating inhibition of adenylate cyclase activity, while D1-type receptors (DRD1 and DRD5) are coupled to G(s) G proteins and promote activation of adenylate cyclase activity (PubMed:10578130, PubMed:33548201, PubMed:37221270, PubMed:39237617). D1- and D2-type dopamine receptors have antagonistic effects, particularly in the brain's striatum, where they govern voluntary movement and reward: D1-type receptors generally stimulate neural activity and promotes action, while D2-type receptors tend to inhibit neural activity and suppress movement (PubMed:10578130, PubMed:33548201, PubMed:37221270, PubMed:39237617). DRD3 is primarily expressed in limbic areas of the brain and is involved in the modulation of cognitive, emotional and motor functions: plays a key role in regulating neuronal signaling pathways associated with motivation, reward and behavior (PubMed:39984436). Involved in the incentive salience of drugs: controls responses to drug-related stimuli, making it a key target for reducing addiction to substances like cocaine, morphine, and alcohol (PubMed:10432116, PubMed:39984436). Forms heterotetramers with DRD1 to potentiate beta-arrestin recruitment and mediate locomotor activity (By similarity). 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 (PubMed:31538542). This leads to activation of ULK1 and initiation of the autophagy cascade (PubMed:31538542). {ECO:0000250|UniProtKB:P30728, ECO:0000269|PubMed:10432116, ECO:0000269|PubMed:10578130, ECO:0000269|PubMed:19520868, ECO:0000269|PubMed:31538542, ECO:0000269|PubMed:33548201, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39237617, ECO:0000269|PubMed:39984436, ECO:0000269|PubMed:8301582}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, Med-Quality Pocket, Druggable Family
- Antibody
- UniProt loc high conf, GO CC high conf, UniProt SigP or TMHMM
- PROTAC
- Small Molecule Binder
- Other modalities
- Approved Drug
gnomAD loss of function constraint: o/e 0.5228300094604492 (upper bound 0.7671599984169006). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 226 registry trials, updated in the last three years, of the most advanced drugs against DRD3 (amoxapine, trifluoperazine, loxapine, apomorphine, tiapride, olanzapine pamoate, cariprazine, promazine, chlorpromazine, pramipexole, haloperidol lactate, levomepromazine), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- David HuiM.D. Anderson Cancer Center · 4 of 4 trials Phase 2+
- David McDonnellAlkermes, Inc. · 2 of 3 trials Phase 2+
- F. Markus LewekeCentral Institute of Mental Health · 2 of 2 trials Phase 2+
- Juan WangSecond Affiliated Hospital, Zhejiang University, School of Medicine · 2 of 2 trials Phase 2+
- Kavita JunejaCorcept Therapeutics · 2 of 2 trials Phase 2+
- Mahavir AgarwalCentre for Addiction and Mental Health · 1 of 2 trials Phase 2+
- Aimee RolstonUniversity of Michigan Rogel Cancer Center · 1 of 1 trials Phase 2+
- Aminah JatoiMayo Clinic · 1 of 1 trials Phase 2+
- Andrew D. KrystalUniversity of California, San Francisco · 1 of 1 trials Phase 2+
- Anurag K SinghRoswell Park Cancer Institute · 1 of 1 trials Phase 2+
- Aslam EjazUniversity of Illinois at Chicago (UIC) · 1 of 1 trials Phase 2+
- Aysegul OzerdemMayo Clinic · 1 of 1 trials Phase 2+
- Benedicto Crespo FacorroAndalusian Health Service · 1 of 1 trials Phase 2+
- Biswa R MishraAll India Institute of Medical Sciences, Bhubaneswar · 1 of 1 trials Phase 2+
- Charles L LoprinziMayo Clinic in Rochester · 1 of 1 trials Phase 2+
Registry trials of amoxapine, trifluoperazine, loxapine, apomorphine, tiapride, olanzapine pamoate, cariprazine, promazine, chlorpromazine, pramipexole, haloperidol lactate, levomepromazine updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 171 of 199 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 27 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
127 trials of drugs against DRD3 were stopped early; 20 give no reason
Terminated, withdrawn and suspended interventional trials of amoxapine, trifluoperazine, loxapine, apomorphine, tiapride, olanzapine pamoate, cariprazine, promazine, chlorpromazine, pramipexole, haloperidol lactate, levomepromazine, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 127.
- terminated · 2026-11-10 · Negovsky Reanimatology Research Institute · matched by the registry's drug synonyms“Financial problems”
- terminated · 2026-09-14 · Denovo Biopharma LLC · matched by the registry's drug synonyms“The decision to stop the trial was based on efficacy results in the overall schizophrenia participant population.”
- terminated · 2026-09-02 · The Guthrie Clinic · matched by the registry's drug synonyms“Study stopped due to lower than expected accrual.”
- withdrawn · 2026-07-28 · Icahn School of Medicine at Mount Sinai · matched by the registry's drug synonyms“Enrollment was discontinued after limited accrual prevented feasible completion of the trial.”
- suspended · 2026-07-14 · National Institute of Allergy and Infectious Diseases (NIAID) · Pramipexole ER“Temporarily Closed (Paused) to Accrual”
- withdrawn · 2026-04-14 · New York State Psychiatric Institute · Cariprazine“Funding decision”
- withdrawn · 2026-03-09 · Universidad Europea de Canarias · matched by the registry's drug synonyms“Study not initiated prior to enrollment.”
- terminated · 2026-02-25 · Ohio State University · matched by the registry's drug synonyms“Not able to recruit enough subjects”
- terminated · 2025-12-15 · Areteia Therapeutics · Dexpramipexole Dihydrochloride“Program stopped due to the benefit risk profile no longer supports further development in the intended patient population.”
- terminated · 2025-12-15 · Areteia Therapeutics · Dexpramipexole Dihydrochloride“Program stopped due to the benefit risk profile no longer supports further development in the intended patient population.”
- terminated · 2025-12-15 · Areteia Therapeutics · Dexpramipexole Dihydrochloride“Program stopped due to the benefit risk profile no longer supports further development in the intended patient population.”
- terminated · 2025-10-21 · Alexza Pharmaceuticals, Inc. · Apomorphine Cartridge“Administrative decision”
- terminated · 2025-10-20 · AbbVie · Cariprazine“Strategic considerations”
- terminated · 2025-09-22 · Massachusetts General Hospital · Pramipexole“An interim analysis indicated that we would need to enroll more subjects than our initial enrollment target, in order to demonstrate a significant treatment effect. Due to these results, we have decided to terminate this protocol.”
- withdrawn · 2025-07-29 · United States Naval Medical Center, Portsmouth · matched by the registry's drug synonyms“No recruitment occurred and PI retired”
- terminated · 2025-06-24 · Third People's Hospital, Huzhou City, Zhejiang Province, China · matched by the registry's drug synonyms“the sponsor has determined that access to the full dataset is no longer available”
- terminated · 2025-06-18 · University of Michigan Rogel Cancer Center · matched by the registry's drug synonyms“Lack of Patient Population”
- terminated · 2025-05-21 · Corewell Health South · matched by the registry's drug synonyms“Lost too many patients to follow up, unable to enroll enough patients”
- terminated · 2024-12-27 · Central Institute of Mental Health, Mannheim · matched by the registry's drug synonyms“Following the expiry of the original research grant, no follow-up financing could be provided to complete the study.”
- terminated · 2024-10-26 · Lakshmi N Yatham · Cariprazine“Research support no longer available.”
- withdrawn · 2024-09-19 · Clinical Academic Center (2CA-Braga) · Pramipexole“This clinical trial was not approved by the regulatory entities. It was reviewed and a new trial was re-submitted.”
- withdrawn · 2024-07-10 · Centre Hospitalier St Anne · CHLORPROMAZINE (CPZ)“No favourable opinion obtained from the Ethics Committee”
- terminated · 2024-05-28 · Assistance Publique - Hôpitaux de Paris · Intramuscular loxapine“Sponsor decision:”
- withdrawn · 2024-05-06 · Mayo Clinic · matched by the registry's drug synonyms“Closed due to slow accrual”
- terminated · 2024-04-23 · Mylan Pharmaceuticals Inc · matched by the registry's drug synonyms“during Period 1 due to numerous orthostatic AEs that occurred. Subsequently, RLD was reduced to 5 mg due to safety concerns.”
Paediatric incentives and obligations for DRD3's drugs
For amoxapine, trifluoperazine, loxapine, apomorphine, tiapride, olanzapine pamoate, cariprazine, promazine, chlorpromazine, pramipexole, haloperidol lactate, levomepromazine: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · DRD3 is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMEA-001652-PIP01-14-M06 (cariprazine hydrochloride, Treatment of schizophrenia): RPM: decision refers to a refusal on the application for modification of an agreed PIP, 6 Jan 2025; EMEA-001115-PIP01-10-M08 (loxapine, Treatment of bipolar disorder;Treatment of schizophrenia): PM: decision on the application for modification of an agreed PIP, 10 Jun 2023Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/06/349 positive 16 Feb 2006: Treatment of off-periods in Parkinson's disease not responding to oral treatment; EU/3/12/954 positive 9 Feb 2012: Treatment of amyotrophic lateral sclerosis; EU/3/11/862 positive 13 May 2011: Treatment of moderate and severe traumatic brain injury; EU/3/01/072 withdrawn 5 Dec 2001: Treatment of off-periods in Parkinson's disease not responding to other oral treatmentRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Zypadhera: authorised since 19 Nov 2008; Sifrol: authorised since 13 Oct 1997; Mirapexin: authorised since 23 Feb 1998; Reagila: authorised since 13 Jul 2017; +8 moreRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of amoxapine, trifluoperazine, loxapine, apomorphine, tiapride, olanzapine pamoate, cariprazine, promazine, chlorpromazine, pramipexole, haloperidol lactate, levomepromazineRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 92 interventional studies of amoxapine, trifluoperazine, loxapine, apomorphine, tiapride, olanzapine pamoate, cariprazine, promazine, chlorpromazine, pramipexole, haloperidol lactate, levomepromazine include patients under 18; 8 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-12
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 45 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.