AMPA/kainate receptor Inhibitors
5 drugsAbout AMPA/kainate receptor
The AMPA/kainate receptor is an ionotropic glutamate receptor crucial for excitatory neurotransmission in the central nervous system. These receptors are ligand-gated ion channels that open upon binding of glutamate, AMPA, or kainate, allowing ion flow and nerve signal propagation.
Human genetic studies provide strong validation for targeting AMPA/kainate receptors, with variants in GRIA1 linked to intellectual developmental disorders (score 0.86) and schizophrenia (score 0.66). Loss-of-function variants are associated with increased risk of intellectual developmental disorders, while gain-of-function variants may protect against schizophrenia.
Five FDA-approved small molecule drugs target AMPA/kainate receptors, including TOPIRAMATE, EPRONTIA, TOPAMAX, TROKENDI XR and QUDEXY XR. These drugs, marketed by companies like Johnson & Johnson and AZURITY, are primarily used for CNS disorders, though one drug has applications in other therapeutic areas.
AMPA/kainate receptor Genetic Evidence Strong
GRIA1 has strong genetic support with a max score of 0.86 linking it to multiple diseases.
The strong genetic support suggests a higher probability of clinical success for novel therapeutics targeting this receptor.
💡 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/kainate receptor Drugs
Five companies have approved drugs, indicating a moderately competitive landscape.
The presence of multiple players suggests moderate barriers to entry, but differentiation is key.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| TROKENDI XR | SUPERNUS PHARMS | 2013 | 5 |
| TOPIRAMATE | Teva | 2003 | 4 |
AMPA/kainate receptor Drug Modality Landscape
Modalities
Routes of Administration
AMPA/kainate receptor is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or gene therapies could offer a competitive advantage.
AMPA/kainate receptor Clinical Trials 95 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on AMPA/kainate receptor. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 16 | 14 | 1 | 1 | 93% |
| Phase 2 | 30 | 19 | 7 | 4 | 73% |
| Phase 3 | 13 | 8 | 5 | 0 | 62% |
| Phase 4 | 36 | 21 | 5 | 8 | 81% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
AMPA/kainate receptor Drug Approval Timeline (1996 - 2021)
The first drug was approved in 1996, and the most recent in 2021, spanning 26 years.
The recent approval suggests continued interest, but market saturation may be a concern.
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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: 66 (15 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/kainate receptor. A trial counts if an approved drug acting on AMPA/kainate 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.