NMDAR Inhibitors
3 drugsAbout NMDAR
The N-methyl-D-aspartate receptor (NMDAR) is a glutamate-gated ion channel essential for excitatory neurotransmission in the central nervous system. It plays a crucial role in synaptic plasticity, learning, and memory processes within the brain.
Human genetic studies provide strong validation for NMDAR (GRIN1) as a therapeutic target, with variants linked to neurodevelopmental disorders (score 0.97). Loss-of-function variants are associated with increased disease risk, suggesting activation-based therapies may be beneficial.
NMDAR is targeted by 3 FDA-approved small molecule drugs including GOCOVRI, AUVELITY and MEMANTINE HYDROCHLORIDE AND DONEPEZIL HYDROCHLORIDE for CNS conditions. These drugs underscore the clinical relevance of NMDAR modulation.
Strategic Insights
ℹ️ How we calculate- White space opportunity in End Stage Renal Disease with only 2 trials.
Human Genetic Evidence Strong
NMDAR (GRIN1) has strong genetic support with a maximum score of 0.97 across 23 diseases.
Strong genetic support increases the likelihood of clinical success, warranting further investment in NMDAR-targeted therapies.
💡 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 Drugs
Three companies, including AXSOME and SUPERNUS PHARMS, have approved drugs targeting NMDAR.
The relatively low number of companies suggests moderate barriers to entry, making it an attractive target for new players.
Drug Modality Landscape
Modalities
Routes of Administration
NMDAR is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or peptides could provide a competitive advantage in the NMDAR space.
Clinical Trials 295 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 83 | 67 | 10 | 6 | 87% |
| Phase 2 | 101 | 66 | 15 | 20 | 81% |
| Phase 3 | 51 | 31 | 11 | 9 | 74% |
| Phase 4 | 60 | 43 | 14 | 3 | 75% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Drug Approval Timeline (1996 - 2022)
Diagnostic procedures (not requiring muscle relaxation)
Alzheimer's Disease
Pseudobulbar Affect
The first NMDAR-targeting drug was approved in 2017, with the most recent approval in 2022.
The recent approval suggests continued interest and potential for further development in NMDAR-targeted therapies.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 3 companies competing
- • Market share by company
Full Drug Portfolio
- • All 3 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 3-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Competition: High (15 sponsors)
- • White space: 10 underexplored indications
- • Success rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Calculate These Metrics
Target Attractiveness Score
A 0-100 score based on trial activity, sponsor diversity, and completion rates. Calculated from 143 clinical trials targeting NMDAR.
Completion rate: Percentage of trials that reached their planned endpoint. Trials terminated early, withdrawn, or suspended are not counted—these often indicate safety issues, lack of efficacy, or strategic pivots.
- Highly Attractive (80+): High trial activity, many sponsors, strong completion rates
- Attractive (60-79): Good trial activity and validation
- Moderate (40-59): Moderate interest from sponsors
- Low (under 40): Limited trial activity or validation concerns
Strategic Insights
Auto-generated insights based on trial analytics including competition intensity, white space opportunities, modality shifts, and failure patterns. We analyze trial sponsors, phases, indications, and outcomes.
Risk Signals
- High Competition: Many sponsors competing for this target (may reduce market opportunity)
- High Failure Risk: Low trial completion rates suggest development challenges
- Low Validation: Limited trial activity or poor outcomes indicate uncertain viability
- White Space Available: Underexplored indications present opportunities