AMPA receptor Inhibitors
5 drugsAbout AMPA receptor
The AMPA receptor (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor) is an ionotropic transmembrane receptor that binds glutamate, mediating fast synaptic transmission in the central nervous system. This process is critical for learning, memory, and neuronal plasticity.
Human genetic studies provide strong validation for targeting GRIA1 (AMPA receptor), with variants linked to intellectual developmental disorder (score 0.86) and schizophrenia (score 0.66). Loss-of-function variants are associated with increased risk of intellectual developmental disorder, while gain-of-function variants appear protective for schizophrenia, suggesting potential therapeutic strategies.
AMPA receptors are targeted by 5 FDA-approved small molecule drugs including PERAMPANEL (FYCOMPA) and QSYMIA. These drugs are used across CNS disorders, pain, and metabolic indications, with PERAMPANEL receiving the most recent approval in 2025.
AMPA receptor Genetic Evidence Strong
GRIA1 has strong genetic support with a max score of 0.86 linking it to multiple diseases.
Strong genetic support suggests that clinical trials targeting GRIA1 have an increased likelihood of success.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 67% directional consistency across 3 traits
- • Strong signal in nervous system disease, genetic, familial or congenital disease pathways
Cross-Disease Effects
Trade-off: ModerateDirection of Effect
67% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link GRIA1 to 50 diseases.
Loss-of-function causes disease; activation may help
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 1 strong
max H4: 0.97eQTL/pQTL signals for GRIA1 colocalize with these GWAS traits, providing causal evidence that gene expression changes drive disease risk.
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 AMPA receptor Drugs
The competitive landscape includes 5 companies with approved drugs, such as STEVENS J, Hikma, and MSN.
The relatively fragmented market suggests lower barriers to entry for new companies targeting AMPA receptors.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| PERAMPANEL | TARO | 2025 | 3 |
| BUTALBITAL, ACETAMINOPHEN, CAFFEINE AND CODEINE PHOSPHATE | Hikma | 2001 | 1 |
AMPA receptor Drug Modality Landscape
Modalities
Routes of Administration
AMPA receptor is amenable to small molecule drugs, with oral options available for convenient dosing.
The absence of other modalities like antibodies or biologics represents a whitespace opportunity for innovation.
AMPA receptor Clinical Trials 1,172 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on AMPA receptor. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 233 | 184 | 17 | 29 | 92% |
| Phase 2 | 246 | 156 | 39 | 50 | 80% |
| Phase 3 | 238 | 132 | 38 | 67 | 78% |
| Phase 4 | 455 | 259 | 83 | 113 | 76% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
2 Phase 3 trials testing approved AMPA receptor drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting AMPA receptor. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
AMPA receptor Drug Approval Timeline (2012 - 2025)
The approval timeline spans 31 years, from 1995 to 2025, with the most recent approval being PERAMPANEL.
The continued approvals indicate sustained interest and potential for further drug development in this area.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 5 companies competing
- • Market share by company
Full Drug Portfolio
- • All 5 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 5-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 584 (116 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 AMPA receptor. A trial counts if an approved drug acting on AMPA 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.