Cycloserine
| 證據等級: L5 | 預測適應症: 7 個 |
目錄
Cycloserine: From Multidrug-Resistant Tuberculosis to Irritable Bowel Syndrome
One-Sentence Summary
Cycloserine is a second-line antibiotic established as a key treatment for multidrug-resistant tuberculosis (MDR-TB), used when first-line agents have failed. The TxGNN model predicts it may be effective for Irritable Bowel Syndrome (IBS), yet 0 clinical trials and 0 publications currently support this direction. The prediction is based entirely on knowledge graph inference (Evidence Level L5), and the recommended decision is Hold pending any form of preclinical validation.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Multidrug-resistant tuberculosis (MDR-TB) |
| Predicted New Indication | Irritable Bowel Syndrome |
| TxGNN Prediction Score | 99.95% |
| Evidence Level | L5 |
| Philippines Market Status | ✗ Not Marketed |
| Number of Registrations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in this evidence pack. Based on known information, cycloserine is a natural D-amino acid analogue antibiotic that inhibits bacterial cell wall synthesis by blocking two enzymes critical to peptidoglycan biosynthesis: D-alanine racemase and D-Ala-D-Ala ligase. Its established clinical role is as a second-line MDR-TB agent, used in combination regimens when isoniazid and rifampicin resistance is confirmed.
Beyond its antibiotic activity, the D-isomer (D-cycloserine) is also known to act as a partial agonist at the glycine co-agonist binding site of NMDA receptors in the central nervous system. Notably, NMDA receptors are also present throughout the enteric nervous system (ENS) — the network of neurons embedded in the gut wall (Auerbach’s plexus and Meissner’s plexus). In theory, D-cycloserine could modulate enteric neuronal excitability, potentially influencing gut motility, visceral pain signalling, and secretomotor function — all pathways implicated in IBS.
However, this mechanistic chain is highly indirect: TB antibiotic → NMDA receptor partial agonism → enteric nervous system modulation → IBS symptom relief. The TxGNN high prediction score most likely reflects multi-hop connectivity within the knowledge graph rather than any direct experimental evidence. No preclinical studies, animal models, or clinical trials investigating cycloserine specifically for IBS were identified. This prediction remains a purely computational hypothesis and should not be advanced without laboratory confirmation.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available.
Philippines Market Information
Cycloserine is currently not registered in the Philippines. No product authorizations were found in the regulatory database.
Safety Considerations
Please refer to the package insert for safety information.
⚠️ Important Safety Signal Identified During Evidence Review
Evidence collected during evaluation of the “insomnia” indication (Rank 5 prediction) reveals a critical concern: the existing evidence direction shows that cycloserine causes insomnia and psychosis as adverse drug reactions — it is emphatically not a treatment for insomnia.
- A 2022 case report (PMID 36712725) documents cycloserine-induced insomnia and psychosis in an MDR-TB patient.
- Three clinical trials retrieved for the insomnia query (NCT03216356, NCT05395494, NCT03395392) all target psychiatric indications (PTSD, fibromyalgia, bipolar depression) via NMDA modulation — none target insomnia as a primary endpoint, and one has been withdrawn.
This CNS toxicity profile — including insomnia, psychosis, seizures, depression, and peripheral neuropathy — represents a substantial safety barrier for any repurposing pathway in non-life-threatening conditions such as IBS.
Conclusion and Next Steps
Decision: Hold
Rationale: There is no clinical or preclinical evidence supporting cycloserine for irritable bowel syndrome, and the drug’s well-documented CNS adverse effect burden (insomnia, psychosis, seizures) makes the benefit-risk ratio unfavorable for a functional gastrointestinal disorder where safer therapeutic alternatives already exist.
To proceed, the following is needed:
- MOA documentation: Obtain formal DrugBank/primary source data on D-cycloserine’s NMDA partial agonist activity and its pharmacological reach into the enteric nervous system
- Preclinical studies: In vitro and animal model experiments examining cycloserine’s effects on gut motility, visceral hypersensitivity, and the ENS — specifically in IBS-relevant models (e.g., post-infectious IBS, stress-induced visceral pain)
- CNS safety profiling: Establish whether enteric-targeted dosing strategies (e.g., modified-release formulations) could achieve GI exposure while minimizing systemic CNS penetration
- Comparative advantage analysis: Clarify what clinical gap cycloserine could fill compared to established IBS treatments (antispasmodics, low-dose antidepressants, rifaximin for IBS-D), given that these already target relevant pathways with well-characterised safety profiles
- Philippines regulatory pathway: Since cycloserine is not registered in the Philippines, any clinical development would require a full new drug application — confirm whether compassionate use or research IND pathways are viable options
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.