Methylergometrine
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Methylergometrine
- Pharmacist Assessment Report
- Methylergometrine: From Uterotonic Use to hypertrichosis (disease) (Top Prediction)
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- India Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Methylergometrine: From Uterotonic Use to hypertrichosis (disease) (Top Prediction)
One-Sentence Summary
Methylergometrine is an ergot-derived drug marketed in India as tablets and injections, with no approved-indication text recorded in the licence data compiled for this report. The TxGNN model’s top prediction is hypertrichosis, but there are 0 clinical trials and 0 publications behind it. Of the ten predictions, only migraine disorder has any related literature (2 reviews), and these offer indirect and safety-oriented context rather than efficacy evidence.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the licence data compiled for this report |
| Predicted New Indication | Hypertrichosis (disease) |
| TxGNN Prediction Score | 0.9987 |
| Evidence Level | L5 |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| Recommended Decision | Hold |
The ten predictions all score between 0.9957 and 0.9987. The table below shows how the evidence differs between them.
| Rank | Predicted Indication | Score | Evidence Level | Recommendation |
|---|---|---|---|---|
| 1 | Hypertrichosis | 0.9987 | L5 | Hold |
| 2 | Pulmonary hypertension | 0.9986 | L5 | Hold |
| 3 | Migraine disorder | 0.9984 | L4 | Research Question |
| 4 | Ambras type hypertrichosis universalis congenita | 0.9982 | L5 | Hold |
| 5 | Malformation syndrome with odontal/periodontal component | 0.9981 | L5 | Hold |
| 6 | Syndrome with Dandy-Walker malformation as major feature | 0.9981 | L5 | Hold |
| 7 | Isolated genetic hair shaft abnormality | 0.9979 | L5 | Hold |
| 8 | Kyphoscoliotic heart disease | 0.9977 | L5 | Hold |
| 9 | Migraine with brainstem aura | 0.9977 | L5 | Hold |
| 10 | Nephrogenic syndrome of inappropriate antidiuresis | 0.9957 | L5 | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, methylergometrine is an ergot-derived uterotonic acting on serotonin, dopamine and alpha-adrenergic receptors.
Hypertrichosis (rank 1): No plausible mechanistic link was identified. Hypertrichosis is a hair growth disorder, and it is a known adverse effect of some other drugs (for example minoxidil). The high score may therefore reflect artifacts of the knowledge network rather than therapeutic potential.
Pulmonary hypertension (rank 2): The mechanistic direction argues against benefit. Ergot derivatives acting on 5-HT2B receptors are associated with pulmonary hypertension and valvulopathy, and methylergometrine has vasoconstrictive activity. This is a potential harm signal.
Migraine disorder (rank 3): This is the only prediction with a plausible, though indirect, link. Methylergometrine is the active metabolite of methysergide, a historical migraine preventive acting on 5-HT receptors. Ergot alkaloids such as ergotamine and dihydroergotamine are established migraine therapies. However, vasoconstriction and coronary risk, along with the fibrotic complications that led to methysergide’s restriction, are major concerns.
Other predictions (ranks 4–8, 10): These are rare congenital or genetic conditions, structural malformations, or disorders with unrelated pathways (for example, a vasopressin V2 receptor gain-of-function disorder). None has a known mechanistic link, and the scores come from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence.
Migraine with brainstem aura (rank 9): A serotonergic rationale exists by extension from migraine, but vasoconstrictive agents such as ergots and triptans are generally cautioned or contraindicated in this subtype because of ischemic concerns.
Clinical Trial Evidence
Currently no related clinical trials are registered for any of the ten predicted indications.
Literature Evidence
Only the migraine disorder prediction has related literature.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 18644039 | 2008 | Review | Cephalalgia | History of methysergide in migraine, from Wolff’s vasodilation theory and the discovery of serotonin to the synthesis of methysergide from lysergic acid |
| 9665056 | 1998 | Review | Circulation | Compared the coronary vasoconstrictor potential of antimigraine drugs, including methylergometrine (the metabolite of methysergide); a safety-oriented study |
Neither paper provides direct efficacy evidence for methylergometrine in migraine. No literature is available for the other nine predictions.
India Market Information
There are 20 valid single-ingredient registrations and no cancelled ones. The licence data contain no approved-indication text. Main authorisations:
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 133630 | Methergin Injection (Novartis India Ltd) | Vial of 1 ml injection | Not recorded |
| 135150 | Methargo Tablet (Mankind Pharma Ltd) | Strip of 10 tablets | Not recorded |
| 129554 | Limitex 0.2mg Injection (Sun Pharmaceutical Industries Ltd) | Vial of 1 ml injection | Not recorded |
| 134492 | Methygene 0.125mg Tablet (Intas Pharmaceuticals Ltd) | Strip of 10 tablets | Not recorded |
| 145497 | Metermin 0.2mg Injection (Cadila Pharmaceuticals Ltd) | Vial of 1 ml injection | Not recorded |
Products are available as oral tablets (0.125 mg) and injections (0.125 mg and 0.2 mg per ml).
Safety Considerations
- Disease contraindications flagged in the knowledge graph (not taken from label text): hypertensive disorder, hypertension, epilepsy, kidney disease, pyoureter, liver disease, gallbladder disease, stroke disorder, cerebrovascular disorder, susceptibility to ischemic stroke, cerebral infarction, arteriosclerosis obliterans, HELLP syndrome.
- Drug interactions: 92 known interactions were identified. Examples rated Major: isometheptene, epinephrine (including ophthalmic and topical forms), ephedrine (including nasal), lorcaserin, and clarithromycin. Examples rated Moderate: doxycycline, tetracycline, minocycline, aprepitant, dexamethasone, cimetidine, and the azoles clotrimazole and miconazole. CYP3A4 inhibitors raise the risk of ergotism.
- Class concerns: vasoconstriction, coronary risk, and pulmonary hypertension or valvulopathy (5-HT2B) are particular concerns for the predicted indications.
Package insert warnings and contraindications were not available for this report; please refer to the package insert.
Conclusion and Next Steps
Decision: Hold
Rationale:
- Nine of the ten predictions rest on model scores alone, with no trials or literature, and several have a mechanistic direction that suggests harm (pulmonary hypertension, kidney disease, stroke risk). Migraine is the only candidate worth further study, and only as a research question, since its literature is indirect and focuses on safety.
To proceed, the following is needed:
- Package insert warnings and contraindications from the Indian regulatory sources (a blocking gap for safety screening)
- Mechanism of action data, for example from DrugBank
- For migraine: a focused literature review of direct efficacy data, and a cardiovascular and fibrosis risk assessment given the vasoconstrictive profile and the 92 interactions
- Approved indication text for the Indian licences, to confirm the original indication
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.