5-HT2A receptor Inhibitors
21 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.
5-HT2A receptor 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 5-HT2A receptor 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 |
|---|---|---|---|
| ARIPIPRAZOLE | Teva | 2015 | 3 |
| SAPHRIS | AbbVie | 2009 | 3 |
| ABILIFY MAINTENA KIT | OTSUKA | 2013 | 3 |
| PALIPERIDONE | Dr. Reddy's | 2015 | 2 |
| CLOZAPINE | ACCORD HLTHCARE | 1996 | 2 |
| ABILIFY ASIMTUFII | OTSUKA | 2023 | 2 |
| SEROQUEL | CHEPLAPHARM | 1997 | 2 |
| ERZOFRI | LUYE INNOMIND PHARMA | 2024 | 2 |
| LATUDA | SUNOVION PHARMS INC | 2010 | 2 |
| VERSACLOZ | DOUGLAS PHARMS | 2013 | 2 |
| VRAYLAR | AbbVie | 2015 | 2 |
| INVEGA SUSTENNA | Johnson & Johnson | 2009 | 2 |
| SECUADO | HISAMITSU PHARM CO | 2019 | 1 |
| TONMYA | TONIX | 2025 | 1 |
| ARISTADA | ALKERMES | 2015 | 1 |
| INVEGA HAFYERA | Johnson & Johnson | 2015 | 1 |
| INVEGA TRINZA | Johnson & Johnson | 2015 | 1 |
| ARISTADA INITIO KIT | ALKERMES | 2018 | 1 |
5-HT2A receptor 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.
5-HT2A receptor Clinical Trials 469 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on 5-HT2A receptor. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 64 | 58 | 1 | 5 | 98% |
| Phase 2 | 54 | 32 | 13 | 9 | 71% |
| Phase 3 | 170 | 127 | 23 | 19 | 85% |
| Phase 4 | 181 | 115 | 38 | 28 | 75% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
5-HT2A receptor 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.
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Deep insights for drug target analysis
Competitive Landscape
- • 15 companies competing
- • Market share by company
Full Drug Portfolio
- • All 21 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 21-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 200 (65 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 5-HT2A receptor. A trial counts if an approved drug acting on 5-HT2A 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.