Methotrimeprazine
| Evidence Level: L5 | Predicted Indications: 6 |
Table of Contents
Methotrimeprazine: Manic bipolar affective disorder
One-Sentence Summary
Methotrimeprazine (levomepromazine) is a phenothiazine with antipsychotic, sedative and analgesic properties. The TxGNN model predicts it may be useful for manic bipolar affective disorder, but the supporting literature consists only of 6 publications, all dated 1961–1964 and descriptive, with no registered clinical trials.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Manic bipolar affective disorder |
| TxGNN Prediction Score | 0.9990 |
| Evidence Level | L5 |
| Canada Market Status | Marketed (marketed DINs: 5 of 5) |
| Number of DINs | 5 (marketed: 5) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on its known pharmacology, methotrimeprazine is a phenothiazine antipsychotic that antagonizes dopamine D2, serotonin 5-HT2A, histamine H1, alpha-1 adrenergic and muscarinic receptors.
D2/5-HT2A blockade underlies the antimanic effect of antipsychotics as a class, so the prediction is mechanistically plausible. Sedation from H1 and alpha-1 blockade may also help control agitation in acutely disturbed patients.
However, the evidence is thin. The available publications are 1960s uncontrolled or descriptive reports on managing acutely disturbed or restless patients, and none of them studies manic bipolar affective disorder directly. For that reason the evidence level is capped at L5 (model prediction with no direct study), despite the plausible mechanism.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
None of these reports directly studies manic bipolar affective disorder; they are general psychiatric reports and are listed as indirect context.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 14129294 | 1964 | Clinical report | Am J Psychiatry | Use of methotrimeprazine to control acutely disturbed patients |
| 14112288 | 1963 | Clinical report | J Neuropsychiatry | Systematic clinical studies with levomepromazine |
| 14341892 | 1964 | Clinical report | Zh Nevropatol Psikhiatr Im S S Korsakova | Evaluation of treatment in depressive conditions |
| 14116226 | 1964 | Pharmacological/clinical report | Compr Psychiatry | Potentiation of phenothiazine effects by nylidrin |
| 14161539 | 1964 | Clinical report | L’Encephale | Treatment of neuroleptic-induced syndromes |
| 14182040 | 1964 | Retrospective observational | Psychiatria et Neurologia | Effect of drug therapy on rehospitalization in chronic psychoses |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02238406 | METHOPRAZINE | Not listed | Not listed |
| 02238403 | METHOPRAZINE | Not listed | Not listed |
| 01927698 | NOZINAN | Not listed | Not listed |
| 02238405 | METHOPRAZINE | Not listed | Not listed |
| 02238404 | METHOPRAZINE | Not listed | Not listed |
All five licences are single-ingredient products and currently valid.
Safety Considerations
- Drug Interactions: Interaction screening returned 100 entries. Major-level interactions include bupropion and potassium citrate. Moderate-level interactions include metformin, pioglitazone and other antidiabetic agents, epinephrine, morphine, atropine and other anticholinergics, famotidine, loperamide, clarithromycin and others. Combined use with sedatives, anticholinergics and glucose-lowering drugs needs careful review.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The mechanism is plausible and the TxGNN score is high, but the only supporting literature is a handful of 1960s descriptive reports that do not directly study manic bipolar affective disorder, and no clinical trials exist. Modern antipsychotics and mood stabilizers already have much stronger evidence in this setting.
To proceed, the following is needed:
- Package insert warnings and contraindications from Health Canada
- Detailed mechanism of action data
- Controlled studies, or at least modern observational data, in acute mania
- A comparison against current standard antimanic therapy
- A safety review addressing sedation, hypotension, QT prolongation and blood dyscrasia risk, which is relevant to a phenothiazine
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.