Chlorzoxazone
| Evidence Level: L5 | Predicted Indications: 9 |
Table of Contents
Chlorzoxazone: From Skeletal Muscle Relaxant Use to Migraine Disorder
One-Sentence Summary
Chlorzoxazone is an oral, centrally acting skeletal muscle relaxant that is marketed in the US as generic tablets. The TxGNN model predicts it may be effective for migraine disorder, but there are 0 registered clinical trials and only 3 indirect publications, none of which studies chlorzoxazone in migraine. The prediction is best treated as a research question, not clinical evidence.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Skeletal muscle relaxant use (label indication text is not included in the provided US license records) |
| Predicted New Indication | Migraine disorder |
| TxGNN Prediction Score | 99.73% |
| Evidence Level | L4 (preclinical/mechanistic signal only) |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 authorizations (all listed examples are generic ANDAs) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in the DrugBank record provided. Based on the available information, chlorzoxazone is a centrally acting muscle relaxant that is known to activate Ca²⁺-activated K⁺ channels (SK/IK). That is the only mechanistic link to migraine.
One preclinical study (PMID 23115190) found that activators of Ca²⁺-dependent K⁺ channels reduced ataxia caused by enhanced CaV2.1 calcium currents in mutant mice. CaV2.1 dysfunction (the CACNA1A gene) is also implicated in familial hemiplegic migraine. This suggests a plausible channelopathy-based hypothesis: modulating K⁺ channels might counterbalance CaV2.1 hyperactivity.
This is only a hypothesis. The study is in mice and does not involve chlorzoxazone or migraine patients. The two vertigo and ataxia reviews are background only. The 99.73% TxGNN score is a computational prediction from the knowledge graph, not proof of efficacy.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 23115190 | 2012 | Preclinical/Animal | J Neurosci | In Cacna1a S218L mutant mice, Ca²⁺-dependent K⁺-channel activators alleviated ataxia caused by enhanced CaV2.1 currents. CACNA1A mutations are linked to ataxia, hemiplegic migraine and epilepsy. |
| 27083881 | 2016 | Review | J Neurol | Overview of drug treatment for cerebellar and central vestibular disorders (e.g., 4-aminopyridine for downbeat nystagmus). Background only. |
| 24000301 | 2013 | Review | Dtsch Arztebl Int | Treatment and natural course of peripheral and central vertigo. Vestibular migraine accounts for about 11.4% of cases. Background only. |
None of these papers evaluates chlorzoxazone in migraine.
US Market Information
Five of the 20 authorizations are shown. All are oral tablets named Chlorzoxazone. The provided records do not include approved indication text.
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| ANDA089859 | Chlorzoxazone | Tablet | Bryant Ranch Prepack |
| ANDA089859 | Chlorzoxazone | Tablet | Actavis Pharma, Inc. |
| ANDA212743 | Chlorzoxazone | Tablet | Endo USA, Inc. |
| ANDA214702 | Chlorzoxazone | Tablet | Lifsa Drugs LLC |
| ANDA089853 | Chlorzoxazone | Tablet | REMEDYREPACK INC. |
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: There are no clinical trials and no studies of chlorzoxazone in migraine. The only support is a preclinical K⁺-channel/CaV2.1 hypothesis plus the TxGNN score. This is a research question, not a candidate ready for clinical development.
To proceed, the following is needed:
- Package insert warnings and contraindications (a blocking gap for safety screening)
- Confirmed mechanism-of-action data from DrugBank, including SK/IK channel activity and its relevance to CaV2.1-related migraine
- Preclinical or mechanistic studies testing chlorzoxazone directly in migraine models, especially familial hemiplegic migraine
- Confirmed US label indication text
Among the other predicted indications, rheumatoid arthritis has the most literature. It is limited to old, uncontrolled reports and a 2012 Cochrane review of muscle relaxants for RA pain, whose conclusions need manual review. Any role there would be symptomatic pain and spasm relief, not disease modification.
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before any application.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.