5-HT1D Inhibitors
16 drugsAbout 5-HT1D
The 5-HT1D receptor is a G protein-coupled receptor that mediates serotonin effects in the central nervous system, playing a key role in neurotransmission. As a serotonin receptor subtype, it is an important drug target, particularly for CNS disorders.
Human genetic studies provide weak support for 5-HT1D as a therapeutic target, with the highest score of 0.25 linking it to ovarian neoplasm and central nervous system infection. There are also 20 strong eQTL/pQTL signals, suggesting potential for further investigation.
5-HT1D is targeted by 9 FDA-approved small molecule drugs, including SUMATRIPTAN and FROVATRIPTAN. These drugs, developed by 8 companies including LANNETT CO INC and GSK, are used to treat CNS disorders.
5-HT1D Genetic Evidence
Genetic evidence for 5-HT1D is weak, with a max score of 0.25 for ovarian neoplasm and central nervous system infection.
Further research is needed to validate 5-HT1D as a drug target based on genetic evidence, despite strong eQTL/pQTL signals.
Evidence Across Diseases
4 totalGWAS and other genetic studies link HTR1D to 4 diseases.
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for HTR1D 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-HT1D Drugs
Eight companies have approved drugs targeting 5-HT1D, with LANNETT CO INC and GSK as top players.
The presence of multiple companies suggests a competitive market, requiring differentiation for new entrants.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| FROVATRIPTAN SUCCINATE | PHARMOBEDIENT | 2014 | 2 |
| SUMATRIPTAN | PERRIGO UK FINCO | 2016 | 2 |
| ZOLMITRIPTAN | Apotex | 2013 | 1 |
| RIZATRIPTAN BENZOATE | Apotex | 2012 | 1 |
| SYMBRAVO | AXSOME | 2025 | 1 |
| MAXALT-MLT | Merck | 1998 | 1 |
| RELPAX | UPJOHN | 2002 | 1 |
| ALMOTRIPTAN MALATE | Viatris | 2015 | 1 |
| TOSYMRA | TONIX MEDS | 2019 | 1 |
| MAXALT | Merck | 1998 | 1 |
| TRUDHESA | IMPEL PHARMS | 2021 | 1 |
| ONZETRA XSAIL | AZURITY | 2016 | 1 |
| ATZUMI | SATSUMA PHARMS | 2025 | 1 |
5-HT1D Drug Modality Landscape
Modalities
Routes of Administration
5-HT1D is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or biologics could provide a competitive advantage in targeting 5-HT1D.
5-HT1D Clinical Trials 238 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on 5-HT1D. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 66 | 59 | 5 | 2 | 92% |
| Phase 2 | 54 | 44 | 9 | 1 | 83% |
| Phase 3 | 58 | 49 | 8 | 1 | 86% |
| Phase 4 | 60 | 43 | 8 | 9 | 84% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
5-HT1D Drug Approval Timeline (1998 - 2025)
The first drug targeting 5-HT1D was approved in 1992 (IMITREX STATDOSE), and the most recent was in 2019 (TOSYMRA).
The approval timeline indicates a mature market, suggesting limited opportunities for novel drug approvals.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 14 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: 131 (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 5-HT1D. A trial counts if an approved drug acting on 5-HT1D 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.