Nitroprusside
| Evidence Level: L4 | Predicted Indications: 9 |
Table of Contents
- Nitroprusside
- Pharmacist Assessment Report
- Nitroprusside: From Hypertensive Emergencies (Intravenous Vasodilator) to Migraine Disorder
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Canada Market Information
- Safety Considerations
- Other Predicted Indications (for reference)
- Conclusion and Next Steps
- Disclaimer
Nitroprusside: From Hypertensive Emergencies (Intravenous Vasodilator) to Migraine Disorder
One-Sentence Summary
Nitroprusside is an intravenous nitric oxide (NO) donor and vasodilator. Its original indication is not listed in the Canadian licence data compiled for this report. The TxGNN model predicts it may be effective for migraine disorder, but the supporting evidence consists of 0 clinical trials and 20 publications, almost all preclinical or mechanistic. The literature suggests nitroprusside and other NO donors provoke migraine-like symptoms rather than relieve them, so the direction of effect is unfavourable for therapy.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available in the licence data compiled for this report |
| Predicted New Indication | Migraine disorder |
| TxGNN Prediction Score | 0.9999 |
| Evidence Level | L4 (preclinical and mechanistic studies only) |
| Canada Market Status | Marketed (marketed DINs: 4 of 5; cancelled: 1) |
| Number of DINs | 5 (marketed: 4) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the database. Based on general pharmacology, nitroprusside releases nitric oxide, which activates soluble guanylate cyclase and raises cGMP, relaxing vascular smooth muscle.
This NO-cGMP pathway, together with CGRP-mediated vasodilation, is clearly involved in migraine biology. Human physiology studies have compared NO and CGRP responses in the peripheral microcirculation of migraine patients and controls, and found endothelial and vascular smooth muscle differences. This is probably why the model links the drug to migraine.
However, the link points the wrong way for treatment. NO donors, including sodium nitroprusside, are used as migraine triggers in mouse models, and the related donor glyceryl trinitrate provokes migraine attacks in patients. Nitroprusside is therefore better viewed as a research or challenge agent than a candidate therapy. The high model score likely reflects pathway association, not therapeutic benefit.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
The following are the most informative publications. None is an RCT.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 18384419 | 2008 | Human physiology study | Cephalalgia | Compared skin microvascular responses to CGRP and NO in migraine patients and controls |
| 16396667 | 2006 | Human physiology study | Cephalalgia | Compared forearm vascular responses to nitroprusside and CGRP in 10 migraine patients and 10 controls |
| 19528518 | 2009 | Human physiology study | Neurology | Vascular smooth muscle cell dysfunction in migraine patients |
| 21122149 | 2010 | Cross-sectional | BMC Neurology | Tested whether endothelial function is impaired in migraine patients |
| 39988876 | 2025 | Preclinical (mouse) | Cephalalgia | CBD and THC reduced migraine-like behaviours triggered by CGRP, sodium nitroprusside and cortical spreading depolarization |
| 36697259 | 2023 | Preclinical (rodent) | J Neurosci | Peroxynitrite contributes to migraine-like behaviour in NO-donor and stress models |
| 38215227 | 2024 | Preclinical (mouse) | Cephalalgia | CGRP receptor antagonism reduced motion sickness indicators in mouse migraine models |
| 11921057 | 2002 | Mechanistic | Ann Neurol | NO donors such as nitroprusside increase iNOS expression; NF-kB proposed as a migraine therapy target |
| 23152076 | 2013 | Preclinical (mouse) | Eur J Pain | St. John’s wort relieved pain in a migraine model induced by NO donors |
| 6745825 | 1984 | Clinical (case series) | Fortschr Med | Nitroprusside treated ergotism (arterial spasm from ergotamine taken for migraine) in 12 cases; this concerns a drug complication, not migraine itself |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02542129 | SODIUM NITROPRUSSIDE FOR INJECTION | Not listed | Not listed |
| 02361736 | NIPRIDE | Not listed | Not listed |
| 02479109 | SODIUM NITROPRUSSIDE FOR INJECTION | Not listed | Not listed |
| 02507404 | SODIUM NITROPRUSSIDE FOR INJECTION | Not listed | Not listed |
| 02450089 | SODIUM NITROPRUSSIDE FOR INJECTION | Not listed | Not listed |
Safety Considerations
- Drug Interactions: 58 interactions were identified. The 20 listed in the compiled data are all moderate severity. They include corticosteroids (hydrocortisone, prednisone, prednisolone, dexamethasone, betamethasone, budesonide, triamcinolone), SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin), opioids (morphine, opium), cannabinoids (dronabinol, nabilone), and others such as bupropion, promethazine, amifostine, sapropterin and iodide I-123.
- Other concerns noted in the evidence: Systemic hypotension and cyanide toxicity are key concerns with IV nitroprusside.
Please refer to the package insert for warnings and contraindications.
Other Predicted Indications (for reference)
| Rank | Predicted Indication | Evidence Level | Note |
|---|---|---|---|
| 2 | Migraine with brainstem aura | L5 | Only indirect migraine physiology studies; no therapeutic rationale |
| 3–6 | Alopecia, congenital hypotrichosis milia, diffuse alopecia areata, hypotrichosis simplex of the scalp | L5 | No trials or literature; computational prediction only |
| 7 | Migraine with or without aura, susceptibility to | L4 | Preclinical and mechanistic literature; supports NO-cGMP biology, not benefit |
| 8 | Pulmonary hypertension | L3 | Most plausible mechanistically (pulmonary vasodilation); a small perioperative study compared inhaled nitroprusside with inhaled prostacyclin and NO; the single listed trial is not about pulmonary hypertension |
| 9–10 | Benign prostatic hyperplasia, kyphoscoliotic heart disease | L5 | No supporting evidence |
Pulmonary hypertension (L3) has stronger evidence than migraine and may be a better focus for follow-up, although nitroprusside lacks pulmonary selectivity and risks systemic hypotension.
Conclusion and Next Steps
Decision: Hold
Rationale: There are no clinical trials for migraine, and the literature is preclinical or mechanistic. It indicates that nitroprusside triggers migraine-like symptoms, so a therapeutic benefit is not supported. The drug is also an intravenous agent for acute hemodynamic control, which is poorly suited to a chronic or episodic outpatient condition such as migraine.
To proceed, the following is needed:
- Package insert warnings and contraindications from Health Canada
- Approved indication text and dosage forms for the Canadian licences
- Mechanism of action data
- Evidence of therapeutic benefit, not provocation, in migraine
- If a new indication is pursued, consider a closer review of pulmonary hypertension, with a safety plan covering hypotension and cyanide toxicity
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.