GRIN1 glutamate ionotropic receptor NMDA type subunit 1
ENSG00000176884 · protein coding · Open Targets profile
Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+) (PubMed:21376300, PubMed:26875626, PubMed:26919761, PubMed:28126851, PubMed:28228639, PubMed:36959261, PubMed:7679115, PubMed:7681588, PubMed:7685113). NMDARs participate in synaptic plasticity for learning and memory formation by contributing to the long-term potentiation (LTP) (PubMed:26875626). Channel activation requires binding of the neurotransmitter L-glutamate to the GluN2 subunit, glycine or D-serine binding to the GluN1 subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:21376300, PubMed:26875626, PubMed:26919761, PubMed:27164704, PubMed:28095420, PubMed:28105280, PubMed:28126851, PubMed:28228639, PubMed:36959261, PubMed:38538865, PubMed:7679115, PubMed:7681588, PubMed:7685113). NMDARs mediate simultaneously the potassium efflux and the influx of calcium and sodium (By similarity). Each GluN2 or GluN3 subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, Ca2(+) permeability, and binding to allosteric modulators (PubMed:26875626, PubMed:26919761, PubMed:36309015, PubMed:38598639). {ECO:0000250|UniProtKB:P35438, ECO:0000269|PubMed:21376300, ECO:0000269|PubMed:26875626, ECO:0000269|PubMed:26919761, ECO:0000269|PubMed:27164704, ECO:0000269|PubMed:28095420, ECO:0000269|PubMed:28105280, ECO:0000269|PubMed:28126851, ECO:0000269|PubMed:28228639, ECO:0000269|PubMed:36309015, ECO:0000269|PubMed:36959261, ECO:0000269|PubMed:38538865, ECO:0000269|PubMed:38598639, ECO:0000269|PubMed:7679115, ECO:0000269|PubMed:7681588, ECO:0000269|PubMed:7685113}.
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 Withdrawn means the drug was pulled from the market or from development.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 loc med conf, UniProt SigP or TMHMM
- PROTAC
- Half-life Data, Small Molecule Binder
- Other modalities
- Advanced Clinical
gnomAD loss of function constraint: o/e 0.36880001425743103 (upper bound 0.48339998722076416). 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 400 registry trials, updated in the last three years, of the most advanced drugs against GRIN1 (amantadine, orphenadrine, acamprosate calcium, felbamate, esketamine, ketamine, acamprosate, memantine, ralfinamide, AV-101, radiprodil, neramexane), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Dong-Xin WangPeking University First Hospital · 16 of 16 trials Phase 2+
- Gisèle PICKERINGUniversity Hospital, Clermont-Ferrand · 3 of 3 trials Phase 2+
- Carlos A ZarateNational Institute of Mental Health (NIMH) · 2 of 4 trials Phase 2+Ph1NCT03973268 · Mechanism of Action Underlying Ketamine's Antidepressant Effects: The AMPA Throughput Theory in Patients With Treatment-Resistant Major Depressionbrief
- Arthur WinerPrincipal Investigator · 2 of 2 trials Phase 2+
- James MurroughIcahn School of Medicine at Mount Sinai · 2 of 2 trials Phase 2+
- Jennifer PhillipsThe University of Ottawa Institute of Mental Health Research (IMHR) at The Royal · 2 of 2 trials Phase 2+
- Madhukar TrivediProfessor (Tenured) · 2 of 2 trials Phase 2+
- Paulo R ShiromaMinneapolis Veterans Affairs Medical Center · 2 of 2 trials Phase 2+
- Vinai GondiNRG Oncology · 2 of 2 trials Phase 2+
- Amy R DeipolyiCAMC Department of Interventional Radiology · 1 of 2 trials Phase 2+
- Balwinder SinghMayo Clinic · 1 of 2 trials Phase 2+
- Rebecca B PriceUniversity of Pittsburgh · 1 of 2 trials Phase 2+
- Adi CosicUniversity Hospitals · 1 of 1 trials Phase 2+
- Ahmed ElhaddadFaculty of medicins,Cairo university · 1 of 1 trials Phase 2+
- Ahmed Ismail Abdel SabourNewValley University · 1 of 1 trials Phase 2+
Registry trials of amantadine, orphenadrine, acamprosate calcium, felbamate, esketamine, ketamine, acamprosate, memantine, ralfinamide, AV-101, radiprodil, neramexane 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; 362 of 374 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. 26 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
281 trials of drugs against GRIN1 were stopped early; 9 of the 200 most recent give no reason
Terminated, withdrawn and suspended interventional trials of amantadine, orphenadrine, acamprosate calcium, felbamate, esketamine, ketamine, acamprosate, memantine, ralfinamide, AV-101, radiprodil, neramexane, 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 281.
- withdrawn · 2026-11-06 · University of Wisconsin, Madison · Ketamine“Budgeting/funding”
- terminated · 2026-11-05 · Dr. Inge Winter · Esketamine Nasal Product, Ketamine Hydrochloride, Esketamine hydrochloride“The site in Israel stopped recruitment due to logistic reasons. Other sites are recruiting for 2023-506602-39-00, 2023-506605-19-00, 2023-506617-21-00.”
- terminated · 2026-10-28 · University of Kansas Medical Center · matched by the registry's drug synonyms“Recruitment challenges.”
- terminated · 2026-10-22 · Ciusss de L'Est de l'Île de Montréal · Ketamine Hydrochloride, dexmedetomidine Hydrochloride and Ketamine Hydrochloride“Not enough funding. recruitment less than anticipated”
- withdrawn · 2026-10-19 · Soterix Medical · Ketamine (0.25 mg/kg), Ketamine (0.5 mg/kg), Ketamine (0.75 mg/kg)“Funding was not provided”
- withdrawn · 2026-10-07 · University of Texas Southwestern Medical Center · Ketamine Hydrochloride“It was not possible to recruit any patients to this study as neurosurgery is placing external ventricular drains and nearly no intra-cranial pressure monitors. No patients recruited or approached. No data collected.”
- terminated · 2026-09-30 · Union Hospital, Tongji Medical College, Huazhong University of Science and Technology · Esketamine hydrochloride“Due to changes in the study plan, no significant clinical benefit was observed, but no adverse events occurred either.”
- terminated · 2026-09-18 · Pusan National University Yangsan Hospital · Ketamine“The study was terminated early due to the principal investigator's transition to another institution.”
- terminated · 2026-09-15 · Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) · Esketamine“slow recruitment.”
- withdrawn · 2026-08-14 · KK Women's and Children's Hospital · S Ketamine“Change of protocol title”
- terminated · 2026-08-12 · Mayo Clinic · Ketamine Hydrochloride“Lack of funding”
- suspended · 2026-07-27 · University of Southern California · 80mg/day Ketamine HCl Prolonged Release, 160mg/day Ketamine HCl Prolonged Release“Difficulty clearing through the FDA”
- withdrawn · 2026-06-30 · Jacques E. Chelly · matched by the registry's drug synonyms“Study did not receive funding.”
- terminated · 2026-06-15 · Wake Forest University Health Sciences · Ketamine“Study initially suspended following an audit and need of amendment to address deficiencies. PI requested to terminate due to lack of support.”
- terminated · 2026-06-04 · Beth Israel Deaconess Medical Center · matched by the registry's drug synonyms“Study terminated due to lack of enrollment.”
- suspended · 2026-05-26 · New York State Psychiatric Institute · Ketamine hydrochloride injection“The U.S. Department of Health and Human Services (HHS) Office of Human Research Protections (OHRP) issued an FWA restriction on NYSPI research that also included a pause of human subjects research as of June 23, 2023.”
- terminated · 2026-05-22 · OrthoCarolina Research Institute, Inc. · matched by the registry's drug synonyms“Low enrollment and subject followup rates”
- terminated · 2026-05-20 · NRG Oncology · Memantine“Inadequate accrual rate”
- suspended · 2026-05-20 · Global Coalition for Adaptive Research · matched by the registry's drug synonyms“Deferred at this time”
- withdrawn · 2026-05-11 · University Hospitals Cleveland Medical Center · ketamine“Study never opened”
- terminated · 2026-05-05 · University Hospital, Lille · Memantine“sponsor decision”
- terminated · 2026-04-06 · University of Oklahoma · Acamprosate“Recruitment barriers.”
- withdrawn · 2026-02-27 · University of New Mexico · Memantine Hydrochloride“Loss of Departmental support”
- withdrawn · 2026-02-25 · Jay Fournier · Intravenous Ketamine“This study never started enrollment at this site. Delays in establishing the infrastructure for this project resulted in the funds no longer being available at this time. Should additional funds be secured, a separate study will be registered here.”
- terminated · 2026-02-25 · Massachusetts General Hospital · Memantine Hydrochloride“requested by the IRB”
Paediatric incentives and obligations for GRIN1's drugs
For amantadine, orphenadrine, acamprosate calcium, felbamate, esketamine, ketamine, acamprosate, memantine, ralfinamide, AV-101, radiprodil, neramexane: 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 · GRIN1 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 · EMA/PE/0000245997 (ketamine;sufentanil, Treatment of acute pain): PM: decision on the application for modification of an agreed PIP, 13 Jun 2025; EMA/PE/0000224110 (esketamine hydrochloride, Treatment of major depressive disorder): PM: decision on the application for modification of an agreed PIP, 28 Jan 2025; EMEA-003462-PIP01-23 (radiprodil, Treatment of GRIN-related disorder): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 13 Jun 2024; EMEA-003337-PIP01-22 (diclofenac;orphenadrine (citrate), Treatment of pain): W: decision granting a waiver in all age groups for all conditions or indications, 31 Jan 2023; +4 moreRule: 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/3/25/3061 positive 22 May 2025: Treatment of GRIN-related neurodevelopmental disorder; EU/3/14/1337 positive 15 Oct 2014: Treatment of fragile X syndromeRule: 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 · Memantine Mylan: authorised since 21 Apr 2013; KemSu: opinion under re-examination; Ebixa: authorised since 15 May 2002; Memantine Accord: authorised since 3 Dec 2013; +10 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 amantadine, orphenadrine, acamprosate calcium, felbamate, esketamine, ketamine, acamprosate, memantine, ralfinamide, av-101, radiprodil, neramexaneRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 371 interventional studies of amantadine, orphenadrine, acamprosate calcium, felbamate, esketamine, ketamine, acamprosate, memantine, ralfinamide, av-101, radiprodil, neramexane include patients under 18; 63 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, 2026-11-11
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 31 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.