Midodrine
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Midodrine: Variably protease-sensitive prionopathy
One-Sentence Summary
Midodrine is an oral alpha-1 adrenergic agonist originally used to treat orthostatic hypotension and related autonomic disorders (multiple system atrophy, postural orthostatic tachycardia syndrome). The TxGNN model’s top-ranked prediction is variably protease-sensitive prionopathy, but no clinical trials and no publications support it. It rests on a TxGNN model (deep learning) score alone, which may reflect similarities the model learned between related diseases, not biological evidence.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Variably protease-sensitive prionopathy |
| TxGNN Prediction Score | 0.9999 |
| 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 |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the compiled records. Midodrine is known to be a prodrug whose active metabolite, desglymidodrine, is a peripheral alpha-1 adrenergic agonist. It raises arteriolar and venous tone and therefore blood pressure. This fits its use in orthostatic hypotension.
Variably protease-sensitive prionopathy is a neurodegenerative protein-misfolding disease. No identifiable mechanistic link connects alpha-1 vasoconstriction to prion pathology. The very high score (0.9999) comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence. At most, midodrine might offer symptomatic relief of autonomic dysfunction if it occurred in these patients. It would not modify the disease.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available.
India Market Information
Midodrine has 20 valid single-ingredient registrations, all oral tablets, and none is cancelled. The registration records contain no approved-indication text. Five main registrations:
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 35010 | Cipmido 5mg Tablet (Cipla Ltd) | Strip of 30 tablets | Not stated in registration records |
| 136336 | Midorise 10 Tablet (Torrent Pharmaceuticals Ltd) | Strip of 10 tablets | Not stated in registration records |
| 134466 | Midora Tablet (Dr Reddy’s Laboratories Ltd) | Strip of 30 tablets | Not stated in registration records |
| 108355 | Inramed 5 Tablet (Mylan Pharmaceuticals Pvt Ltd) | Strip of 10 tablets | Not stated in registration records |
| 133846 | Midodrive Tablet (Sun Pharmaceutical Industries Ltd) | Strip of 20 tablets | Not stated in registration records |
Safety Considerations
- Knowledge-graph contraindication signals (from drug-disease contraindication edges, not label text): adrenal gland pheochromocytoma, phaeochromocytoma, sympathetic paraganglioma, adrenal gland cancer, duodenum cancer, small intestine cancer, heart cancer, thyrotoxicosis, hyperthyroidism, Graves disease.
- Drug Interactions: 81 known interactions. Examples:
- Moderate: other sympathomimetics and vasoconstrictors such as epinephrine (including ophthalmic and topical forms), ephedrine, phentermine, diethylpropion, mazindol, sibutramine and isometheptene. Also bupropion, lorcaserin, trospium, rolapitant and glycerol phenylbutyrate.
- Minor: ranitidine, cimetidine and metformin.
- Pharmacological cautions from the evaluation: supine hypertension (avoid late-day dosing), urinary retention, and reflex bradycardia or conduction problems.
Please refer to the package insert for the full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction has no trials, no literature and no plausible mechanistic link, so it is purely computational (L5).
Best-supported alternative among the model’s predictions: hypotensive disorder (score 0.9990, evidence level L2, Proceed with Guardrails). It is backed by one completed Phase 2 trial, NCT02893553 (n=21, hypotension in spinal cord injury), and several reviews and guideline-type papers, plus a randomised trial of midodrine with octreotide in hepatorenal syndrome (PMID 25644760). This is largely a re-confirmation of the existing orthostatic hypotension use, not true repurposing.
To proceed, the following is needed:
- Any preclinical or clinical rationale linking midodrine to prion disease, or a decision to deprioritise this prediction
- Detailed mechanism of action data
- Package insert warnings and contraindications for India-marketed products, plus the approved-indication text
- A safety plan covering supine hypertension, bradycardia and the many drug interactions
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.