Oxitriptan
| 證據等級: L5 | 預測適應症: 1 個 |
目錄
Oxitriptan: From No Approved Indication to Insomnia
One-Sentence Summary
Oxitriptan (5-hydroxytryptophan, 5-HTP) currently has no approved indication and is not marketed in Taiwan. The TxGNN model predicts it may be effective for Insomnia, with 6 clinical trials and 13 publications currently identified, though most evidence is preclinical or only indirectly related.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available — drug is unmarketed with no recorded approved indication |
| Predicted New Indication | Insomnia |
| TxGNN Prediction Score | 99.89% |
| Evidence Level | L4 |
| Market Status | Not Marketed |
| Number of NDAs | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available (MOA field is a data gap). Based on the information available, oxitriptan (5-HTP) is a direct precursor of serotonin biosynthesis — it is metabolized via the serotonergic pathway and can be further converted to melatonin through N-acetylation and methylation. This pathway provides a theoretical basis for a role in sleep regulation, and is the same rationale underlying over-the-counter 5-HTP supplements marketed for sleep support.
However, since original_indications is empty and the drug is not currently marketed in Taiwan, there is no established original indication to compare against. The link to insomnia should therefore be regarded as a mechanistic hypothesis derived from serotonin/melatonin physiology rather than a validated repurposing relationship. Most supporting literature uses PCPA (p-chlorophenylalanine)-induced insomnia animal models to study the serotonergic (5-HT) system broadly, rather than testing oxitriptan itself — this indirect evidence base is consistent with the mechanistic (not clinical) nature of the current support.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00001918 | N/A | Completed | 20 | Clinical evaluation of L-5-hydroxytryptophan-related eosinophilia-myalgia syndrome (EMS); provides human exposure/safety data for 5-HTP but not an efficacy trial for insomnia |
| NCT06893822 | N/A | Recruiting | 20 | Randomized, double-blind, placebo-controlled crossover study of Griffonia simplicifolia (natural 5-HTP source) on pain and sensitization, not insomnia |
| NCT04078724 | N/A | Completed | 33 | RCT assessing 5-HTP supplementation’s impact on sleep quality and gut microbiome in older adults with normal cognition vs. mild cognitive impairment |
| NCT03364101 | N/A | Completed | 60 | Explored relationship between an experimental “PowerOff” intervention and sleep quality using actigraphy; drug/compound identity unclear |
| NCT06365801 | N/A | Not Yet Recruiting | 100 | Acupoint biological characteristics in irritable bowel syndrome — likely keyword mismatch, not directly relevant |
| NCT06718452 | N/A | Not Yet Recruiting | 100 | umPEALUT for tinnitus targeting neuroinflammation — not directly relevant to oxitriptan or insomnia |
Note: Only NCT00001918 and NCT04078724 involve 5-HTP directly; neither is a controlled efficacy trial of oxitriptan for insomnia specifically. The remaining trials are low-relevance or likely search mismatches.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 2962265 | 1987 | Review | Revue medicale de la Suisse romande | Discusses clinical indications for L-5-hydroxytryptophan in neurology, including sleep-related conditions |
| 4128428 | 1974 | Case Report | Electroencephalography and Clinical Neurophysiology | Reports a favorable effect of 5-hydroxytryptophan in a case of severe prolonged insomnia (agrypnia) associated with Morvan’s disease |
| 33634088 | 2021 | Review | Frontiers in Bioengineering and Biotechnology | Reviews 5-HTP’s physiological roles in sleep, mood, and pain regulation, and its therapeutic use in insomnia, depression, and migraine |
| 32006050 | 2020 | Preclinical | Applied Microbiology and Biotechnology | Describes microbial biosynthesis of 5-HTP, noting its established use for insomnia, depression, and chronic headache |
| 4548556 | 1974 | Case Report | Revue neurologique | Polygraphic/metabolic study of persistent insomnia with hallucinations in a case of Morvan’s fibrillar chorea (companion report to NCT-independent 5-HTP case) |
| 40350945 | 2025 | Animal Model | China Journal of Chinese Materia Medica | Fushen Decoction improved PCPA-induced insomnia in mice via modulation of the 5-HT system and GABA expression, supporting serotonergic relevance to sleep |
| 39710185 | 2024 | Animal Model | Neuroscience Letters | Sleep deprivation impaired pineal melatonin secretion via AMPK/FOXO3a-mediated autophagy inhibition, linking the serotonin-melatonin pathway to insomnia-depression comorbidity |
| 40493075 | 2025 | Animal Model | Psychopharmacology | Ginsenoside Rg1 alleviated PCPA-induced insomnia via NLRP3 inflammasome inhibition through the Nrf2/HO-1 pathway |
| 40367689 | 2025 | Animal Model | International Immunopharmacology | Cinnamic acid promoted sleep in a PCPA-induced insomnia rat model |
| 40160035 | 2025 | Animal Model | International Journal of Neuropsychopharmacology | Nuciferine enhanced rodent sleep via modulation of the serotonergic system |
Note: No RCTs of oxitriptan for insomnia were identified. Direct drug-relevant evidence (2962265, 4128428, 4548556) is old case-level/review literature; the remaining items are mechanistic animal studies of the broader serotonergic pathway in insomnia, using compounds other than oxitriptan.
Market Information
This drug currently has no approved licenses and is not marketed. No product registration data is available for review.
Safety Considerations
Please refer to the package insert for safety information.
Note: TFDA label warnings/contraindications data is a blocking gap (DG001) — this drug cannot yet complete an S1 safety pre-assessment without this information.
Conclusion and Next Steps
Decision: Hold
Rationale: Evidence is limited to L4 (preclinical/mechanistic studies and indirect case reports); no controlled clinical trial has evaluated oxitriptan specifically for insomnia, and the drug is not currently marketed with no established original indication for comparison.
To proceed, the following is needed:
- TFDA label warnings/contraindications (blocking — required for S1 safety pre-assessment)
- Mechanism of action (MOA) documentation from DrugBank to support the mechanistic rationale
- Clinical trials or observational studies directly testing oxitriptan (not other serotonergic agents or 5-HTP-containing supplements) for insomnia
- Clarification of market/regulatory status before further development consideration
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.