5HT2 Inhibitors
16 drugsAbout 5HT2
The 5HT2 receptor family comprises serotonin receptors crucial in the central nervous system. These receptors mediate the effects of serotonin, influencing various physiological and neurological processes.
Human genetic studies provide moderate support for 5HT2 as a therapeutic target, with HTR2A 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 inhibition may be beneficial.
Six FDA-approved small molecule drugs target 5HT2, including RISPERDAL, SEROQUEL, and RYKINDO, all indicated for CNS disorders. These drugs have been approved over a 31-year span, from 1993 to 2023.
5HT2 Genetic Evidence Moderate
Genetic evidence shows moderate support for 5HT2, with a max score of 0.55 for major depressive disorder.
Further investigation of HTR2A variants in depression could reveal novel therapeutic strategies.
💡 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 5HT2 Drugs
Five companies have approved drugs targeting 5HT2, including Johnson & Johnson and STERISCIENCE.
The presence of established players suggests a moderately competitive market with potential entry barriers.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| LYBALVI | ALKERMES | 2021 | 3 |
| PERSERIS KIT | INDIVIOR | 2018 | 3 |
| RYKINDO | SHANDONG LUYE | 2023 | 3 |
| ZIPRASIDONE HYDROCHLORIDE | Dr. Reddy's | 2012 | 2 |
| ZYPREXA | CHEPLAPHARM | 1996 | 2 |
| ZYPREXA ZYDIS | CHEPLAPHARM | 2000 | 2 |
| RISPERDAL | Johnson & Johnson | 1993 | 2 |
| SEROQUEL | CHEPLAPHARM | 1997 | 2 |
| RISPERDAL CONSTA | Johnson & Johnson | 2003 | 2 |
| UZEDY | Teva | 2023 | 2 |
| FANAPT | VANDA PHARMS INC | 2009 | 2 |
| ZYPREXA RELPREVV | CHEPLAPHARM | 2009 | 1 |
| RALDESY | KAMAT | 2024 | 1 |
5HT2 Drug Modality Landscape
Modalities
Routes of Administration
5HT2 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.
5HT2 Clinical Trials 436 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on 5HT2. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 83 | 69 | 5 | 8 | 93% |
| Phase 2 | 99 | 61 | 19 | 18 | 76% |
| Phase 3 | 120 | 78 | 19 | 23 | 80% |
| Phase 4 | 134 | 87 | 31 | 16 | 74% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
3 Phase 3 trials testing approved 5HT2 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting 5HT2. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
5HT2 Drug Approval Timeline (1993 - 2024)
The first 5HT2-targeting drug was approved in 1993, with the most recent in 2023.
The continued approval of new drugs suggests ongoing interest and potential for further innovation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 12 companies competing
- • Market share by company
Full Drug Portfolio
- • All 16 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 16-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 251 (61 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 5HT2. A trial counts if an approved drug acting on 5HT2 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.