NMDA receptor Inhibitors
12 drugsAbout NMDA receptor
The NMDA receptor is a glutamate-gated ion channel protein in nerve cells crucial for synaptic plasticity, learning, and memory. It plays a key role in the central nervous system by mediating excitatory neurotransmission. As such, it is an important target for drug development.
Human genetic studies provide strong validation for NMDA receptor targeting, with variants in GRIN1 linked to neurodevelopmental disorders (score 0.97). Loss-of-function variants are associated with increased disease risk, suggesting activation may be beneficial.
Five FDA-approved drugs target the NMDA receptor, including Felbamate, Nuedexta, and Ketamine Hydrochloride. All approved drugs are small molecules, spanning CNS and other therapeutic areas.
NMDA receptor Genetic Evidence Strong
Strong genetic evidence supports NMDA receptor's role in neurodevelopmental disorders (max score 0.97).
Strong genetic support increases confidence in clinical trials targeting neurodevelopmental disorders.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 3 traits
- • Strong signal in nervous system disease, genetic, familial or congenital disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link GRIN1 to 23 diseases.
Loss-of-function causes disease; activation may help
Loss-of-function causes disease; activation may help
Understanding these scores
Association Score (0-1): Combines all evidence types (genetic, literature, drugs, animal models). Higher = more evidence linking target to disease. This is a ranking heuristic, not a confidence score.
L2G Score: Open Targets uses a machine learning model (Locus-to-Gene) to predict which gene is causal at each GWAS locus. L2G=0.5 means ~50% probability of being the causal gene. Only associations with L2G > 0.05 are included.
Odds Ratio (OR): From gene burden studies (UK Biobank, AstraZeneca PheWAS). Measures how loss-of-function variants affect disease risk. OR<1 = protective (inhibiting target may help), OR>1 = risk (losing function causes disease).
Beta (β): Effect size for continuous traits. β<0 = protective, β>0 = risk.
Clinical Translation (~1.8x): Based on Nelson et al. 2015: drug targets with genetic evidence have ~2x higher success rates in clinical trials. We estimate: Strong support (score ≥0.7) → ~1.8x, Moderate (0.3-0.7) → ~1.3x, Weak → baseline.
Colocalization (H4): Tests whether a GWAS signal and an eQTL/pQTL signal share the same causal variant. H4 is the posterior probability that both traits are associated AND share a causal variant. H4 > 0.8 = strong evidence that gene expression/protein levels drive disease risk. This links genetic variation → gene expression → disease, supporting the target-disease connection.
Top NMDA receptor Drugs
Five companies have approved drugs targeting the NMDA receptor, including ANI PHARMS and AbbVie.
The presence of multiple players suggests a competitive but accessible market.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| KETALAR | PH HEALTH | 1970 | 3 |
| METHADONE HYDROCHLORIDE INTENSOL | Hikma | 1988 | 2 |
| SPRAVATO | Johnson & Johnson | 2019 | 2 |
| DEXTROMETHORPHAN HYDROBROMIDE AND QUINIDINE SULFATE | Sun Pharma | 2017 | 1 |
| MEMANTINE HYDROCHLORIDE AND DONEPEZIL HYDROCHLORIDE | ANI PHARMS | 2017 | 1 |
| NUEDEXTA | OTSUKA AMERICA | 2010 | 1 |
| NAMZARIC | AbbVie | 2014 | 1 |
| AUVELITY | AXSOME | 2022 | 1 |
| METHADONE HYDROCHLORIDE | BRECKENRIDGE | 1947 | - |
NMDA receptor Drug Modality Landscape
Modalities
Routes of Administration
NMDA receptor is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or biologics could provide differentiation.
NMDA receptor Clinical Trials 972 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on NMDA receptor. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 245 | 181 | 31 | 33 | 85% |
| Phase 2 | 275 | 164 | 54 | 55 | 75% |
| Phase 3 | 136 | 71 | 30 | 35 | 70% |
| Phase 4 | 316 | 198 | 57 | 60 | 78% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
NMDA receptor Drug Approval Timeline (1947 - 2022)
1. Methadone Hydrochloride Injection is indicated for the...
Diagnostic procedures (not requiring muscle relaxation)
Alzheimer's Disease
Pseudobulbar Affect
The first NMDA receptor drug was approved in 1996, with the most recent in 2017.
The approval timeline indicates a mature but not saturated market with potential for innovation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 12 companies competing
- • Market share by company
Full Drug Portfolio
- • All 12 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 12-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 481 (83 companies)
- • Completion rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Count Trials
- Trials: phase 1-4 interventional trials on ClinicalTrials.gov that started in 2008 or later and test an FDA-approved drug acting on NMDA receptor. A trial counts if an approved drug acting on NMDA receptor is in any arm, including as a comparator, and a trial that tests two such drugs counts once. Trials that test only unapproved drugs are not counted. A trial listed as phase 1/2 counts as phase 1, and phase 2/3 as phase 2.
- Active: recruiting, not yet recruiting, enrolling by invitation, or active and no longer recruiting.
- Completion rate: of the trials that have ended, the share marked Completed rather than Terminated or Withdrawn. Completed means the trial ended as planned; it does not mean the drug worked. Suspended trials are not counted as ended.
- Stopped: terminated or withdrawn. Trials stop for many reasons, including slow enrolment and business decisions, not only safety or efficacy.
- Sponsors: the lead sponsor of each trial. Companies are the sponsors ClinicalTrials.gov classes as industry; the rest are universities, hospitals, cooperative groups, government bodies and individuals.