5-HT2A receptor Inhibitors
11 drugsAbout 5-HT2A receptor
The 5-HT2A receptor (serotonin 2A receptor) is a serotonin receptor and CNS drug target involved in various neurological processes. As a key neurotransmitter receptor, it modulates neuronal excitability and neurotransmitter release.
Human genetic studies provide moderate support for HTR2A as a therapeutic target, with variants linked to major depressive disorder (score 0.55) and color vision disorder (score 0.47). Loss-of-function variants are protective against major depressive disorder, suggesting that inhibition may be beneficial.
5-HT2A is targeted by 11 FDA-approved small molecule drugs, including CLOZAPINE, ARIPIPRAZOLE, and OPIPZA. These drugs primarily address CNS disorders like schizophrenia and bipolar disorder, though one approved drug targets a non-CNS therapeutic area.
Strategic Insights
ℹ️ How we calculate- White space opportunity in Weight Gain with only 2 trials.
Human Genetic Evidence Moderate
Genetic evidence shows moderate support for HTR2A, with a max score of 0.55 linked to major depressive disorder.
Moderate genetic support suggests further investigation into patient stratification strategies may improve clinical trial outcomes.
💡 Why inhibition?
- • Loss-of-function variants reduce disease risk (OR < 1)
- • 100% directional consistency across 1 traits
- • Strong signal in psychiatric disorder, nervous system disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
16 totalGWAS and other genetic studies link HTR2A to 16 diseases.
Inhibiting this target may be therapeutic
🔗 Colocalization Evidence 1 strong
max H4: 0.98eQTL/pQTL signals for HTR2A 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
Nine companies have approved drugs targeting 5-HT2A, with Teva, UNICHEM, and AbbVie as top players.
The presence of multiple established players suggests a moderately competitive market requiring differentiated strategies for new entrants.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| SAPHRIS | AbbVie | 2009 | 3 |
| CLOZAPINE | Teva | 1996 | 2 |
| VERSACLOZ | DOUGLAS PHARMS | 2013 | 2 |
| VRAYLAR | AbbVie | 2015 | 2 |
| ABILIFY ASIMTUFII | OTSUKA | 2023 | 2 |
| SECUADO | HISAMITSU | 2019 | 1 |
| ARISTADA INITIO KIT | ALKERMES INC | 2018 | 1 |
| ARISTADA | ALKERMES INC | 2015 | 1 |
Drug Modality Landscape
Modalities
Routes of Administration
5-HT2A receptor is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or peptides could offer a competitive advantage in modulating receptor activity.
Clinical Trials 288 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 48 | 43 | 0 | 5 | 100% |
| Phase 2 | 44 | 28 | 10 | 5 | 74% |
| Phase 3 | 102 | 82 | 14 | 5 | 85% |
| Phase 4 | 94 | 60 | 21 | 13 | 74% |
Top Sponsors
By Modality
Top Conditions
Drug Approval Timeline (1996 - 2025)
The first 5-HT2A targeting drug was approved in 1996 (CLOZAPINE), with the most recent approval in 2024 (OPIPZA).
The continued approval of new drugs indicates ongoing innovation and market potential despite the target's long history.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 9 companies competing
- • Market share by company
Full Drug Portfolio
- • All 11 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 11-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 127 clinical trials targeting 5-HT2A 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