GABA-A receptor Inhibitors
6 drugsAbout GABA-A receptor
The GABA-A receptor is a ligand-gated ion channel mediating inhibitory neurotransmission in the central nervous system (CNS) upon GABA binding. Modulation of this receptor is a key therapeutic strategy.
Human genetic studies provide strong validation for GABA-A receptor targeting (max score 0.91), with loss-of-function variants in GABRA1 linked to developmental and epileptic encephalopathy. Activation of GABA-A receptor is likely beneficial based on genetic evidence.
GABA-A receptor is targeted by 23 FDA-approved small molecule drugs, including TOPIRAMATE and ZTALMY. These drugs are developed by 21 companies and address CNS disorders, pain, and other therapeutic areas.
Strategic Insights
ℹ️ How we calculate- White space opportunity in Bipolar I Disorder with only 1 trials.
Human Genetic Evidence Strong
GABA-A receptor has strong genetic support with a max score of 0.91 linking GABRA1 variants to multiple epilepsies.
Strong genetic support suggests a higher probability of clinical success for novel GABA-A receptor modulators.
💡 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
13 totalGWAS and other genetic studies link GABRA1 to 13 diseases.
Loss-of-function causes disease; activation may help
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 3 strong
max H4: 0.97eQTL/pQTL signals for GABRA1 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 Drugs
21 companies have approved GABA-A receptor targeting drugs, with ACCORD HLTHCARE among the top players.
The fragmented competitive landscape suggests relatively low barriers to entry for new GABA-A receptor modulators.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| EPRONTIA | AZURITY | 2021 | 5 |
| TOPIRAMATE | ACCORD HLTHCARE | 2003 | 4 |
| XCOPRI | SK LIFE | 2019 | 1 |
Drug Modality Landscape
Modalities
Routes of Administration
GABA-A 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.
Clinical Trials 124 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 30 | 27 | 1 | 2 | 96% |
| Phase 2 | 32 | 20 | 7 | 5 | 74% |
| Phase 3 | 22 | 11 | 5 | 5 | 69% |
| Phase 4 | 40 | 24 | 6 | 9 | 80% |
Top Sponsors
By Modality
Phase 3 Readout Calendar Pro
4 Phase 3 trials testing approved GABA-A receptor drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting GABA-A receptor. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
Drug Approval Timeline (1996 - 2021)
The first GABA-A receptor drug was approved in 1981 (XANAX), with the most recent in 2022 (ZTALMY).
The continued approvals indicate sustained interest and potential for further innovation in GABA-A receptor modulation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 6 companies competing
- • Market share by company
Full Drug Portfolio
- • All 6 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 6-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 67 clinical trials targeting GABA-A receptor.
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