Doxapram
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Doxapram: From Respiratory Stimulation to Vascular Disease
One-Sentence Summary
Doxapram is an injectable respiratory stimulant marketed in the US under NDA014879. The TxGNN model predicts it may be effective for vascular disease, but there are currently 0 registered clinical trials and 17 retrieved publications, none of which shows benefit in vascular disease. This prediction is best read as a knowledge-graph artifact rather than a pharmacology-based lead.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the source record (approved indication text is empty); doxapram is a respiratory stimulant |
| Predicted New Indication | Vascular disease |
| TxGNN Prediction Score | 99.99% |
| Evidence Level | L4 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 2 (both under NDA014879) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the source record. Doxapram is known as a respiratory stimulant that acts on peripheral chemoreceptors and brainstem respiratory centers. Its established use is in respiratory settings, not vascular ones.
No direct mechanistic link to vascular disease was found. The retrieved literature covers hemodynamic side effects, hypoxic pulmonary vasoconstriction and respiratory use, not treatment of vascular disease. The very high TxGNN score (0.9999) is likely driven by knowledge-graph proximity rather than pharmacology.
The other nine top-ranked predictions are also unsupported. They include arterial, venous and neurogenic thoracic outlet syndrome, angiodysplasia of stomach, blue toe syndrome, hemangioendothelioma, atheroembolism of kidney, visceral calciphylaxis and lymphangiectasis. All have scores above 99.98%, but none has any trial or literature evidence (L5), and none has a plausible pathway from respiratory stimulation.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 40023176 | 2025 | RCT (Phase 3) | Lancet | PRESTIGE-AF: DOACs vs no anticoagulation for stroke prevention after intracerebral haemorrhage with atrial fibrillation. Does not involve doxapram; likely a keyword match. |
| 8737758 | 1996 | Randomized trial / cohort | Eur J Clin Pharmacol | Continuous doxapram infusion vs placebo for late postoperative hypoxaemia; the study reports adverse events. |
| 11743509 | 2001 | Cohort | J Pediatr | Prolonged doxapram therapy for apnea was associated with isolated mental developmental delay in very low birth weight infants. |
| 18371030 | 2008 | Cohort (veterinary) | J Vet Intern Med | Retrospective comparison of caffeine and doxapram for hypercapnia in foals with hypoxic-ischemic encephalopathy. |
| 4397240 | 1971 | Not classified | Proc Soc Exp Biol Med | Doxapram in hemorrhagic hypotension (title only; no abstract available). |
| 4398848 | 1971 | Preclinical (dogs) | Anesth Analg | Hemodynamic responses to doxapram in normovolemic and hypovolemic dogs. |
| 10704775 | 2000 | Preclinical (rats) | Neurosci Lett | Doxapram accentuated white matter injury in neonatal rats after bilateral carotid artery occlusion. |
| 8870121 | 1996 | Preclinical (piglets) | Semin Perinatol | Modulators of hypoxic pulmonary vasoconstriction and the response to inhaled nitric oxide in neonatal atelectasis. |
| 4764360 | 1973 | Not classified | Crit Care Med | Doxapram in the critically ill: whether increased oxygen consumption reflects an oxygen dividend or debt (title only). |
| 4706757 | 1973 | Case report | Anesthesiology | Recovery from central respiratory failure and doxapram administration in a patient with a brainstem lesion. |
None of these publications shows efficacy of doxapram in vascular disease. Most are old, preclinical, veterinary or respiratory-focused.
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA014879 | DOXAPRAM HYDROCHLORIDE (HF Acquisition Co LLC, DBA HealthFirst) | Injection | Not stated in the source record |
| NDA014879 | Dopram (Hikma Pharmaceuticals USA Inc.) | Injection | Not stated in the source record |
Safety Considerations
- Drug Interactions: No interaction records were found in the queried database.
The retrieved literature raises these signals, which need confirmation against the label:
- White matter injury in neonatal rats under cerebral ischemia (PMID 10704775)
- Adverse events during continuous postoperative infusion (PMID 8737758)
- Association of prolonged therapy in preterm infants with neurodevelopmental delay (PMID 11743509)
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests only on a model score. There are no clinical trials, no supportive literature and no plausible mechanism linking a respiratory stimulant to vascular disease. The safety signals in neonates and continuous infusion add further caution.
To proceed, the following is needed:
- Package insert warnings and contraindications, which are currently missing and block safety screening
- Detailed mechanism of action data (for example from DrugBank)
- Approved indication text for NDA014879
- A specific, mechanism-based vascular hypothesis, with preclinical support, before any clinical study
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before any application.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.