Ergometrine

證據等級: L5

預測適應症: 10 個

Ergometrine: From Oxytocic Agent to Migraine Disorder

One-Sentence Summary

Ergometrine is an ergot alkaloid oxytocic agent historically used for preventing and treating postpartum hemorrhage and uterine atony. The TxGNN model generates 10 predicted indications; migraine disorder (rank #7) is the only prediction with biological plausibility and literature support, backed by 20 publications documenting the use of ergometrine and structurally related ergot derivatives in migraine prophylaxis. Critically, two predicted indications — pulmonary hypertension (rank #10) and migraine with brainstem aura (rank #8) — are identified in the retrieved literature as absolute contraindications, not treatment targets; ranks #1–6 appear to be knowledge graph sparsity artifacts with no supporting evidence.

Quick Overview

Item	Content
Original Indication	Postpartum hemorrhage prevention and uterine atony (known pharmacological use; no Health Canada DIN on record)
Most Evidence-Supported Predicted Indication	Migraine disorder (TxGNN rank #7 of 10)
TxGNN Prediction Score	99.93% (migraine, rank #7); highest-ranked prediction hypertrichosis at 99.96% is a KG artifact
Evidence Level	L4 — historical case series and observational studies (migraine); L5 for all other ranked indications
Canada Market Status	Not marketed
Number of DINs	0
Recommended Decision	Hold (Research Question)

Why Is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available in this evidence pack. Based on known pharmacological information, ergometrine (ergonovine) is an ergot alkaloid that acts as a partial agonist at α-adrenergic, serotonin (5-HT₂), and dopamine receptors, producing potent smooth muscle contraction — particularly in the uterus and vascular walls. Its established clinical role is in obstetrics for postpartum uterine contraction and hemorrhage control.

The connection to migraine is grounded in ergot alkaloid pharmacology. Ergot derivatives have a long history as migraine treatments: ergotamine and dihydroergotamine (DHE) remain pharmacopoeial options for acute migraine, and methysergide — explicitly described in the literature (PMID 9793694) as a “semisynthetic ergot alkaloid ergometrine derivative” — was for decades a standard prophylactic agent via 5-HT₁ agonism and 5-HT₂ antagonism. Methylergonovine, the direct N-methyl homolog of ergometrine, has been specifically studied for refractory migraine and cluster headache (PMID 23432443, 19895705). The trigeminal vascular hypothesis of migraine implicates 5-HT₁B/1D receptor–mediated cerebral vasoconstriction as a key therapeutic mechanism, which overlaps directly with ergometrine’s receptor profile.

However, the same vasoconstrictive properties that may confer anti-migraine activity also generate a clinically significant safety burden: coronary artery vasospasm, QT prolongation, hypertensive crisis, and — of particular relevance — reversible cerebral vasoconstriction syndrome (RCVS) in migraine-with-aura patients. Modern migraine management has largely moved away from ergot vasoconstrictors toward triptans and CGRP pathway agents with better tolerability profiles.

Regarding ranks #1–6 and #9: The predictions for hypertrichosis, Ambras syndrome, nephrogenic SIAD, malformation syndrome with periodontal component, Dandy-Walker syndrome, isolated hair shaft abnormality, and leprosy all carry TxGNN scores above 99.8% yet have zero clinical trials, zero relevant literature, and no pharmacological mechanistic link to ergometrine. These are consistent with knowledge graph sparsity artifacts — rare disease nodes with few connections in the KG can produce artificially inflated prediction scores. None should be pursued.

Clinical Trial Evidence

No clinical trials investigating ergometrine for migraine disorder, or for any of the other 9 predicted indications, are currently registered on ClinicalTrials.gov or the WHO ICTRP.

Literature Evidence

The following are the most relevant publications for migraine (rank #7) — the only prediction with genuine supporting evidence. Literature retrieved for ranks #1–6 and #9 is either absent (0 results) or non-contributory (20 periodontology papers with no link to ergometrine, consistent with an indexing artifact). Additional safety signals from ranks #8 and #10 are summarised in a separate table below.

PMID	Year	Type	Journal	Key Findings
2759844	1989	Case Series / Open-label	Headache	40 menstrual migraine patients treated with intermittent prophylactic ergonovine maleate over 6 months; demonstrated meaningful headache reduction — the most direct evidence for ergometrine itself in migraine
23432443	2013	Retrospective Study	Headache	Oral methylergonovine maleate (N-methyl homolog) for refractory migraine and cluster headache prevention; supports ergometrine-class activity in treatment-resistant headache
19895705	2009	Clinical Observational	Head & Face Medicine	Pilot open-label study of intravenous methylergonovine in female ED migraine patients; assessed emergency use, effectiveness, and tolerability
9793694	1998	Review	Cephalalgia	Methysergide described as an “ergometrine derivative”; documents efficacy in migraine prophylaxis including high-frequency resistant cases via 5-HT₁ agonism and 5-HT₂ antagonism
7216754	1980	Observational Study	Headache	Long-term results of interval therapy in migraine including ergot alkaloid regimens; longitudinal tolerability data
5761912	1969	Historical Clinical Study	British Medical Journal	Ergot-class preparations in recurrent headache prophylaxis; historical evidence base for the class
556819	1977	Case Report / Review	Neurology	Carotidynia (vascular neck pain) treated with migraine prophylactics including ergot alkaloids; supports vascular headache mechanistic overlap
23216317	2013	Safety Review	Headache	QT prolongation, torsade de pointes, and myocardial ischaemia from coronary vasospasm with headache medications including ergot alkaloids — critical safety signal for any migraine application
6773347	1980	Case Report	AJR	Pleural thickening caused by Sansert (methysergide) and Ergotrate (ergometrine brand) in migraine treatment — adverse event report directly implicating ergometrine by name
10971665	2000	Case Report	Headache	⚠️ Reversible cerebral vasoconstriction syndrome (RCVS) in a chronic migraine-with-aura patient following postpartum ergometrine — primary safety signal against use in aura-migraine subtypes

⚠️ Contraindication Signals from Predicted Indications #8 and #10

PMID	Predicted Indication (TxGNN rank)	Safety Signal
22731893	Pulmonary hypertension (#10)	Obstetric anaesthesia clinical review explicitly lists ergometrine as contraindicated in pulmonary hypertension due to pulmonary vasoconstriction
26050249	Pulmonary hypertension (#10)	Case report: methylergonovine triggered acute pulmonary hypertensive crisis in a parturient with left ventricular noncompaction
41844474	Pulmonary hypertension (#10)	2026 focused review of uterotonics in cardiac disease reinforces ergometrine/methylergonovine contraindication in pulmonary hypertension
10971665	Migraine with brainstem aura (#8)	RCVS with diffuse intracranial arterial narrowing following ergometrine in migraine-with-aura patient; strong contraindication signal for basilar/brainstem-aura migraine subtype

Canada Market Information

Ergometrine has no Health Canada Drug Identification Numbers (DINs) and is not currently marketed in Canada. No product licence data is available for this analysis.

Ergometrine (ergonovine maleate) may be obtainable through Health Canada’s Special Access Programme (SAP) for exceptional obstetric use, but no formal approval is on record. Any repurposing pathway would require a new drug submission or clinical trial application under Health Canada regulations.

Safety Considerations

No Health Canada package insert is available for this analysis. Based on literature evidence gathered during evidence collection:

Cardiovascular risk: Ergometrine is a potent vasoconstrictor. Literature documents coronary artery vasospasm (Prinzmetal-type angina, PMID 15293589), QT prolongation and torsade de pointes risk (PMID 23216317), and hypertensive crisis. These cardiovascular signals are particularly concerning for any proposed migraine indication given the overlapping cardiovascular comorbidities in migraine populations.
Pulmonary hypertension — absolute contraindication: Multiple independent publications (PMID 22731893, 26050249, 41844474) explicitly identify pulmonary hypertension as a contraindication to ergometrine and methylergonovine. The TxGNN rank #10 prediction is a pharmacovigilance-relevant false positive.
Migraine with brainstem aura — contraindication: PMID 10971665 documents RCVS with cerebral oedema and occipital haemorrhage following ergometrine in a chronic migraine-with-aura patient. Ergometrine’s potent cerebrovascular constriction is likely to exacerbate brainstem-aura physiology. The TxGNN rank #8 prediction is contraindicated.
Fibrotic complications: Prolonged use of ergot alkaloids including ergotrate has been associated with pleural and potentially retroperitoneal fibrosis (PMID 6773347) — a class-level concern for any chronic migraine prophylaxis application.
Obstetric context caution: Literature notes that ergometrine should be avoided in pre-eclampsia (PMID 22731893) and in patients with significant cardiac disease; this population overlaps with some severe migraine patient profiles.

Conclusion and Next Steps

Decision: Hold (Research Question)

Rationale: Ergometrine and its structural relatives (methylergonovine, methysergide) have documented historical use in migraine prophylaxis, providing mechanistic plausibility and limited indirect clinical evidence (L4). However, the cardiovascular safety profile — coronary vasospasm, QT prolongation, RCVS in aura-migraine patients, and absolute contraindication in pulmonary hypertension — significantly narrows any viable therapeutic window, and contemporary migraine therapeutics (triptans, gepants, CGRP monoclonal antibodies) have supplanted vasoconstrictor-class ergot derivatives for both efficacy and safety reasons. No prospective clinical trials exist.

To proceed, the following is needed:

Detailed MOA data from DrugBank to precisely map ergometrine’s receptor binding profile relative to ergotamine and DHE, and to identify any differentiated pharmacological advantage
Full safety data from a Health Canada–recognized source (WHO product monograph, EMEA SmPC, or equivalent) to establish the known contraindication list and monitoring requirements
Patient stratification criteria excluding cardiovascular disease, hypertension, pulmonary hypertension, and migraine-with-aura subtypes before any study design is considered
Comparative positioning analysis versus current standard-of-care (second- and third-line CGRP pathway agents) to define a potential niche, if any, in treatment-resistant migraine without cardiovascular comorbidity
Pharmacovigilance review of the full ergot alkaloid class for cumulative fibrotic and vasospastic risk signals
Health Canada SAP or IND pathway assessment for clinical trial feasibility given the absence of any current Canadian product licence
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.