Mepyramine
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
Mepyramine: Nasal cavity disease
One-Sentence Summary
Mepyramine is a first-generation antihistamine, originally used for allergic conditions such as allergic rhinitis, conjunctivitis, urticaria and angioedema. The TxGNN model predicts it may be effective for nasal cavity disease, but there are currently no registered clinical trials. The 4 publications found are indirect (preclinical studies and one veterinary study), so the evidence is weak.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Nasal cavity disease |
| TxGNN Prediction Score | 0.9974 |
| Evidence Level | L5 |
| Canada Market Status | Marketed (marketed DINs: 2 of 2) |
| Number of DINs | 2 (marketed: 2) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the compiled data. Based on known information, mepyramine is a first-generation histamine H1 receptor antagonist. Histamine is the central mediator of allergic urticaria, so blocking H1 receptors gives a strong mechanistic rationale.
The other predicted indications are less well supported:
- Nasal cavity disease (score 0.9974): a broad category. H1 blockade is relevant to allergic and vasomotor rhinitis, but non-allergic subtypes lack a clear histamine-driven mechanism.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 21033572 | 2010 | Veterinary clinical study | Polish Journal of Veterinary Sciences | In 27 dogs with angioedema (15 treated, 12 placebo controls), mepyramine maleate showed potential benefit |
| 34758144 | 2021 | Preclinical (mechanistic) | FASEB Journal | Mepyramine directly blocks nociceptor voltage-gated sodium channels, suggesting a topical pain-relief effect |
| 18222495 | 2008 | Preclinical (rat neurons) | Neuropharmacology | Mepyramine inhibits the KCNQ/M potassium channel and depolarizes neurons, which may explain the neurotoxicity seen in overdose |
| 29371669 | 2018 | Preclinical (tool compound) | Scientific Reports | Fluorescent H1-receptor probes were developed to study ligand-binding kinetics in living cells |
None of these studies tested mepyramine as a treatment for allergic urticaria in humans.
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02275201 | MIDOL COMPLETE | Not specified | Not specified |
| 02275228 | MIDOL PMS | Not specified | Not specified |
Both licenses are valid authorizations.
Safety Considerations
Contraindications suggested by the knowledge graph (these come from graph relationships, not from package insert text):
- Cardiovascular: hypertension and hypotensive disorders, coronary artery disease, myocardial infarction, coronary thrombosis
- Liver, pancreas and gallbladder: liver failure, liver disease, pancreatitis, gallbladder disease
- Kidney and urinary: kidney disease, pyoureter, benign prostatic hyperplasia
- Respiratory: chronic obstructive pulmonary disease (including severe early onset)
- Neurological and substance use: epilepsy, substance abuse/dependence
- Endocrine and metabolic: hypothyroidism, myxedema, congenital hypothyroidism, diabetes mellitus, diabetic ketoacidosis
- Gastrointestinal: peptic ulcer disease, inflammatory bowel disease, Clostridium difficile colitis, perinatal necrotizing enterocolitis
- Other: rhabdomyolysis, nodular fasciitis, hemoglobinopathy
Drug interactions: The interaction query returned 100 records. The main ones are:
- Major: potassium citrate and potassium chloride
- Moderate:
- Anticholinergics: atropine, hyoscyamine, scopolamine, glycopyrronium, dicyclomine, clidinium, mepenzolate, methscopolamine, propantheline, trospium
- Opioids and antidiarrheals: morphine, opium, loperamide, eluxadoline
- Others: metoclopramide, dronabinol
Preclinical neurotoxicity signal: Overdose of first-generation antihistamines has been linked to seizures and convulsions, and mepyramine inhibits the neuronal KCNQ/M channel.
Please refer to the package insert for official warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale:
- The mechanistic rationale is strong, but the evidence is weak. There are no registered clinical trials, and the literature is indirect: preclinical studies and a veterinary study.
- Urticaria is already a labeled indication, so this is not truly a new use.
- Package insert warnings and contraindications are not yet available, and this gap blocks progression to safety screening.
To proceed, the following is needed:
- The Health Canada package insert for warnings and contraindications
- Mechanism of action data, for example from DrugBank
- Dosage form, manufacturer and indication details for the two Canadian products, which are combination-type brands (MIDOL)
- Human clinical evidence for mepyramine in urticaria, or a clear decision that on-label use needs no repurposing study
- A review of whether the knowledge-graph contraindications apply to the intended population
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.