Cycloserine
| Evidence Level: L5 | Predicted Indications: 7 |
Table of Contents
Cycloserine: From Tuberculosis to Irritable Bowel Syndrome
One-Sentence Summary
Cycloserine is a second-line antitubercular agent (D-alanine racemase/ligase inhibitor) used historically for multidrug-resistant pulmonary tuberculosis, and it is currently not marketed in Taiwan. The TxGNN model predicts it may be effective for Irritable Bowel Syndrome, with a very high prediction score (99.95%), but this is currently supported by zero clinical trials and zero publications — the evidence pack itself flags no known mechanistic link to this indication.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Tuberculosis (multidrug-resistant pulmonary TB) — inferred from literature within this evidence pack; no official TFDA-approved indication text is available since the drug is unregistered in Taiwan |
| Predicted New Indication | Irritable Bowel Syndrome |
| TxGNN Prediction Score | 99.95% |
| Evidence Level | L5 |
| Taiwan Market Status | Not marketed (Not marketed) |
| Number of Registrations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is currently a data gap (DG002). Based on information available within this evidence pack, Cycloserine is known to act as an inhibitor of bacterial D-alanine racemase/ligase (its antitubercular mechanism) and separately as a partial agonist at the NMDA receptor — a property exploited in several psychiatric/neurological trials referenced elsewhere in this pack (e.g., PTSD, bipolar depression).
Neither of these two known mechanisms has an established link to irritable bowel syndrome pathophysiology (gut motility or brain-gut axis signaling). The evidence pack’s own rationale for this candidate is explicit on this point: “No known mechanistic link; cycloserine’s antibacterial and NMDA partial-agonist activity has no direct connection to IBS gut motility/brain-gut axis pathophysiology — this is a pure TxGNN computational prediction with no clinical trial or literature support.”
In other words, the high TxGNN score reflects a statistical association learned from the knowledge graph rather than a biologically or clinically substantiated hypothesis. Note also that among the other candidates in this pack, insomnia (rank 5) has comparatively more real-world evidence (3 trials, 2 case reports) — but that evidence points toward cycloserine causing insomnia as an adverse effect during TB treatment, not treating it, which is the opposite of a repurposing signal.
Clinical Trial Evidence
Currently no related clinical trials registered
Literature Evidence
Currently no related literature available
Safety Considerations
Drug Interactions (from DDI database, 11 total interactions identified):
- Major: Bupropion, Ethanol, Iohexol, Iopamidol
- Moderate: Picosulfuric acid, Polyethylene glycol (3350 with electrolytes), Sodium sulfate, Caffeine, Dicoumarol, Warfarin, Lindane
Detailed key warnings and contraindications are a data gap (DG001, Blocking severity) pending TFDA label retrieval — please refer to the package insert once available.
Conclusion and Next Steps
Decision: Hold
Rationale: The IBS prediction (TxGNN score 99.95%) is a pure model-derived association (L5) with no supporting mechanistic rationale, clinical trials, or literature — the evidence pack itself states there is no known biological connection. Combined with the drug not being marketed in Taiwan and two Blocking/High-severity data gaps (TFDA label, MOA), this candidate does not meet the bar to advance past S0.
To proceed, the following is needed:
- Resolve DG001 (TFDA label warnings/contraindications) — currently Blocking for any safety review
- Resolve DG002 (confirmed mechanism of action via DrugBank)
- Preclinical or mechanistic studies linking cycloserine’s NMDA/antibacterial activity to gut motility or visceral hypersensitivity pathways relevant to IBS
- At minimum, one exploratory clinical study or case series in IBS patients before this candidate can move beyond S0/Hold
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.