Atropine
| Evidence Level: L4 | Predicted Indications: 2 |
Table of Contents
- Atropine
- Atropine: From an Anticholinergic Agent (Original Indication Not Recorded) to Migraine Disorder
Atropine: From an Anticholinergic Agent (Original Indication Not Recorded) to Migraine Disorder
One-Sentence Summary
Atropine is a non-selective muscarinic (anticholinergic) drug, and its original approved indication is not recorded in the data compiled for this report. The TxGNN model predicts it may be effective for migraine disorder, but there are currently 0 clinical trials and only indirect, mostly preclinical literature supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available (no approved indication text in the New Zealand licence records) |
| Predicted New Indication | Migraine disorder |
| TxGNN Prediction Score | 99.56% |
| Evidence Level | L4 |
| New Zealand Market Status | Cancelled only (no currently valid licences) |
| Number of Authorizations | 3 (all cancelled) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available. Based on known information, atropine is a non-selective muscarinic receptor antagonist, so its pharmacology rests on blocking cholinergic signalling. Whether that could be applied to migraine remains unproven.
Several publications suggest that the cholinergic system may take part in migraine pathophysiology. In rats, cholinergic modulation of meningeal mast cells has been linked to neurogenic inflammation in a nitroglycerin-induced migraine model. Stimulating the parasympathetic sphenopalatine ganglion causes plasma protein leakage in the dura mater. Central cholinergic pathways also contribute to antinociception in rodents. In chronic paroxysmal hemicrania, a related headache disorder, systemic atropine reduced attack-related sweating, tearing and nasal secretion.
Together these findings make a role for muscarinic blockade in migraine plausible, but the evidence is indirect and largely animal-based. The high TxGNN score is a computational prediction and is not clinical evidence. A second predicted indication, migraine with brainstem aura (score 99.42%, evidence level L5), has no trials or specific literature and probably reflects its close relationship to the parent disease in the knowledge graph.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Of the retrieved publications, only some are relevant. None tests atropine as a treatment for migraine.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 36485173 | 2024 | Preclinical | Eur J Neurosci | Cholinergic modulation of meningeal mast cells and neurogenic inflammation in a rat migraine model |
| 9344563 | 1997 | Preclinical | Exp Neurol | Parasympathetic sphenopalatine ganglion stimulation induces plasma protein extravasation in rat dura mater |
| 8930196 | 1996 | Preclinical | J Pharmacol Exp Ther | Central cholinergic system contributes to sumatriptan-induced antinociception in rodents |
| 2943405 | 1986 | Clinical observation | Cephalalgia | In four patients with chronic paroxysmal hemicrania, systemic atropine markedly reduced attack-related sweating, tearing and nasal secretion |
| 17186568 | 2007 | Review | J Appl Toxicol | Pharmacology of anisodamine, an atropine derivative and non-specific cholinergic antagonist |
| 10193781 | 1999 | Preclinical | Br J Pharmacol | Effects of migraine-related drugs on nicotine-evoked relaxation of guinea-pig basilar artery (atropine used as a background agent) |
New Zealand Market Information
All three licences are cancelled, and no approved indication text is recorded for any of them.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 2528754 | Martindale | Inj 600 mcg per ml, 1 ml ampoule | Not recorded (cancelled) |
| 2693976 | Hikma | Inj 600 mcg per ml, 1 ml ampoule | Not recorded (cancelled) |
| 200905 | Atropt | Eye drops 1% | Not recorded (cancelled) |
Safety Considerations
- Drug Interactions: 380 known interactions were found. Most of those listed are of Moderate severity, including:
- Opioids: fentanyl, alfentanil, codeine, dihydrocodeine, tramadol
- Other anticholinergic or sedating drugs: amitriptyline, chlorpheniramine, acrivastine, phenyltoloxamine, hyoscyamine, aclidinium, amantadine
- Others: ethanol, botulinum toxin type A, galantamine, acetylcholine, acebutolol, loperamide
Acetaminophen and hydrochlorothiazide interactions are Minor.
- Class effects: Anticholinergic adverse effects (tachycardia, blurred vision, raised intraocular pressure, dry mouth, cognitive effects) would be a concern for chronic or prophylactic use. Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The only support for atropine in migraine is a computational prediction plus indirect, mostly preclinical literature, and no clinical trial has tested it. All New Zealand licences are cancelled, and the anticholinergic side-effect and interaction burden is substantial for a chronic indication.
To proceed, the following is needed:
- Package insert warnings and contraindications from Medsafe (a blocking gap for safety screening)
- Original approved indications and mechanism of action data
- Clinical evidence in migraine, starting with a pilot or exploratory study with a suitable formulation and route
- A risk-benefit assessment of anticholinergic adverse effects and the high interaction burden
- Clarification of the regulatory pathway, since no valid licence currently exists in New Zealand
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.