DRD2 dopamine receptor D2
ENSG00000149295 · 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:21645528, PubMed:32103023, PubMed:32528175, PubMed:33353947, PubMed:33571431, PubMed:37221270, PubMed:39103320). 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:32103023, PubMed:32528175, PubMed:33353947, PubMed:33571431, PubMed:37221270). Dopamine receptors can be classified in two categories: (1) DRD2 (together with DRD3 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:32103023, PubMed:32528175, PubMed:33353947, PubMed:33571431, PubMed:37221270). In the central nervous system, DRD2 is mainly coupled to G(o)/GNAO1 (By similarity). 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 (By similarity). DRD1 and DRD2 are the most abundant dopamine receptors in the central nervous system, especially in the basal ganglia and the prefrontal cortex (PubMed:33571431). DRD2 receptor plays a key role in risky decision-making by modulating reward sensitivity and executive control; DRD2 activation in nucleus accumbens cells leading to increased risk- taking and impulsivity (By similarity). DRD2 can also couple with G(q) by forming a heteromer with the ghrelin receptor GHSR in neurons independently of ghrelin (By similarity). Following DRD2 activation by dopamine in lumbosacral defecation centers, GHSR acts as a coreceptor promoting DRD2 coupling to G(q) at the expense of G(i)/G(o), regulating defecation (By similarity). In addition to dopamine, also acts as a receptor for tryptophan-derived metabolites in intestinal epithelial cells: activation by tryptophan metabolites produced by the gut microbiota initiates a phospholipase-C-dependent signaling that promotes colonization resistance by pathogens by controlling actin cytoskeletal organization in the gut epithelium (By similarity). Positively regulates postnatal regression of retinal hyaloid vessels via suppression of VEGFR2/KDR activity, downstream of OPN5 (By similarity). Also acts as a receptor for D-lysergic (LSD) psychedelic drug (PubMed:40683247). {ECO:0000250|UniProtKB:P61168, ECO:0000250|UniProtKB:P61169, ECO:0000269|PubMed:21645528, ECO:0000269|PubMed:32103023, ECO:0000269|PubMed:32528175, ECO:0000269|PubMed:33353947, ECO:0000269|PubMed:33571431, ECO:0000269|PubMed:37221270, ECO:0000269|PubMed:39103320, ECO:0000269|PubMed:40683247}.
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, 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 0.21047000586986542 (upper bound 0.3797599971294403). 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 60 registry trials, updated in the last three years, of the most advanced drugs against DRD2 (fluphenazine, ergoloid mesylates, benperidol, molindone, quinagolide, amoxapine, haloperidol lactate, levomepromazine, trifluoperazine, tiapride, thiethylperazine, prochlorperazine), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- David HuiM.D. Anderson Cancer Center · 4 of 4 trials Phase 2+
- Alice P ChenNational Cancer Institute (NCI) · 2 of 2 trials Phase 2+
- Aimee RolstonUniversity of Michigan Rogel Cancer Center · 1 of 1 trials Phase 2+
- Asma Al BuraikiOman Medical Speciality Board · 1 of 1 trials Phase 2+
- Azmi NasserSupernus Pharmaceuticals, Inc. · 1 of 1 trials Phase 2+
- Benedicto Crespo FacorroAndalusian Health Service · 1 of 1 trials Phase 2+
- Christopher PitottiMike O'Callaghan Federal Medical Center · 1 of 1 trials Phase 2+
- Dian MardianiFaculty of Medicine Universitas Padjadjaran Bandung · 1 of 1 trials Phase 2+
- Elan SmallUniversity of Colorado, Denver · 1 of 1 trials Phase 2+
- Gianpiera Ceresoli-BorroniSupernus Pharmaceuticals, Inc. · 1 of 1 trials Phase 2+
- Isabelle ChoiProton Collaborative Group · 1 of 1 trials Phase 2+
- Jesper KjaergaardDept. of Cardiology, Rigshospitalet · 1 of 1 trials Phase 2+
- Jessica McCoyWestern Michigan University Homer Stryker M.D. School of Medicine · 1 of 1 trials Phase 2+
- Konstantinos SpaniolasStony Brook University · 1 of 1 trials Phase 2+
- Luke PepponeUniversity of Rochester NCORP Research Base · 1 of 1 trials Phase 2+
Registry trials of fluphenazine, ergoloid mesylates, benperidol, molindone, quinagolide, amoxapine, haloperidol lactate, levomepromazine, trifluoperazine, tiapride, thiethylperazine, prochlorperazine 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; 52 of 54 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. 6 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
52 trials of drugs against DRD2 were stopped early; 8 give no reason
Terminated, withdrawn and suspended interventional trials of fluphenazine, ergoloid mesylates, benperidol, molindone, quinagolide, amoxapine, haloperidol lactate, levomepromazine, trifluoperazine, tiapride, thiethylperazine, prochlorperazine, 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 52.
- terminated · 2026-11-10 · Negovsky Reanimatology Research Institute · matched by the registry's drug synonyms“Financial problems”
- terminated · 2026-01-16 · Washington University School of Medicine · Prochlorperazine“The eligibility criteria within the protocol led to the exclusion of a large proportion of potential participants, thereby limiting enrollment. During the conceptualization phase, the number of eligible patients was overestimated.”
- withdrawn · 2025-08-19 · United States Naval Medical Center, Portsmouth · prochlorperazine and benadryl IV“unable to recruit participants”
- withdrawn · 2025-07-29 · United States Naval Medical Center, Portsmouth · matched by the registry's drug synonyms“No recruitment occurred and PI retired”
- terminated · 2025-06-18 · 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”
- withdrawn · 2024-11-29 · Corewell Health South · matched by the registry's drug synonyms“no longer recruiting or studying”
- withdrawn · 2024-08-07 · Australasian Leukaemia and Lymphoma Group · matched by the registry's drug synonyms“Study halted prematurely, prior to enrollment of first participant due to protracted logistical and subsequent funding matters.”
- terminated · 2024-08-01 · Christian Fromm, MD · prochlorperazine and diphenhydramine.(Standard Treatment)“Insufficient recruitment.”
- terminated · 2024-05-16 · Supernus Pharmaceuticals, Inc. · matched by the registry's drug synonyms“The program was shut down due to a lack of efficacy.”
- withdrawn · 2024-04-02 · Koen van Besien · Prochlorperazine“The original principal Investigator left the institution.”
- terminated · 2024-03-04 · Mike O'Callaghan Military Hospital · matched by the registry's drug synonyms“study goals met”
- terminated · 2023-11-18 · InterveXion Therapeutics, LLC · matched by the registry's drug synonyms“Sponsor decision based on slower than anticipated enrollment leading to fund exhaustion.”
- terminated · 2022-12-14 · Adrianna Vlachos, MD · Trifluoperazine“Supporter terminated study due to slow subject accrual secondary to COVID pandemic limiting travel to research site.”
- terminated · 2022-11-04 · The University of Hong Kong · matched by the registry's drug synonyms“Primary endpoint reached based on data projection from interim analysis.”
- terminated · 2022-11-04 · The University of Hong Kong · matched by the registry's drug synonyms“The study was terminated prematurely due to difficulties in patient recruitment and associated potential for selection bias.”
- terminated · 2022-07-14 · Wake Forest University Health Sciences · matched by the registry's drug synonyms“Unable to enroll adequate number of patients.”
- terminated · 2022-05-11 · Erasmus Medical Center · matched by the registry's drug synonyms“The study was stopped because of futility of being able to reach a one-day difference between treatment groups in the primary outcome of DCFD in the intended sample size.”
- terminated · 2020-11-25 · RWTH Aachen University · matched by the registry's drug synonyms“slow patient recruitment, low patient-commpliance, high dropout rates,”
- terminated · 2020-03-18 · Albert Einstein Healthcare Network · Prochlorperazine 10mg“no difference found between two groups in a preliminary analysis”
- terminated · 2019-06-26 · Stanford University · matched by the registry's drug synonyms“We did not recruit the research assistant and terminated the study”
- terminated · 2019-06-18 · University of California, Davis · matched by the registry's drug synonyms“recruitment futility”
- terminated · 2019-02-15 · University Health Network, Toronto · matched by the registry's drug synonyms“Slow accrual”
- terminated · 2018-11-07 · Merck Sharp & Dohme LLC · matched by the registry's drug synonymsNo reason given
- terminated · 2018-10-23 · OhioHealth · matched by the registry's drug synonyms“PI lapsed institutional training”
Paediatric incentives and obligations for DRD2's drugs
For fluphenazine, ergoloid mesylates, benperidol, molindone, quinagolide, amoxapine, haloperidol lactate, levomepromazine, trifluoperazine, tiapride, thiethylperazine, prochlorperazine: 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 · DRD2 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: no · No EMA paediatric investigation plan decision names fluphenazine, ergoloid mesylates, benperidol, molindone, quinagolide, amoxapine, haloperidol lactate, levomepromazine, trifluoperazine, tiapride, thiethylperazine, prochlorperazineRule: 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: no · No EU orphan designation names fluphenazine, ergoloid mesylates, benperidol, molindone, quinagolide, amoxapine, haloperidol lactate, levomepromazine, trifluoperazine, tiapride, thiethylperazine, prochlorperazineRule: 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: no · EMA lists no centrally authorised medicine of fluphenazine, ergoloid mesylates, benperidol, molindone, quinagolide, amoxapine, haloperidol lactate, levomepromazine, trifluoperazine, tiapride, thiethylperazine, prochlorperazineRule: 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 fluphenazine, ergoloid mesylates, benperidol, molindone, quinagolide, amoxapine, haloperidol lactate, levomepromazine, trifluoperazine, tiapride, thiethylperazine, prochlorperazineRule: 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 · 24 interventional studies of fluphenazine, ergoloid mesylates, benperidol, molindone, quinagolide, amoxapine, haloperidol lactate, levomepromazine, trifluoperazine, tiapride, thiethylperazine, prochlorperazine include patients under 18; 0 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 111 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.