Papaverine

證據等級: L5

預測適應症: 10 個

Papaverine: From Vasospasm Treatment to Ischemic Disease

One-Sentence Summary

Papaverine has long been used clinically as an intra-arterial/intracavernosal vasodilator to prevent or treat vascular spasm (e.g., during CABG graft harvesting, mesenteric ischemia, and coronary flow reserve testing), though it currently holds no formal marketing authorization in this jurisdiction. The TxGNN model predicts it may be effective for Ischemic Disease, with 4 clinical trials and 19 publications currently supporting this direction.

Quick Overview

Item	Content
Original Indication	Not available — no approved indication text found in this jurisdiction’s licensing records
Predicted New Indication	Ischemic Disease
TxGNN Prediction Score	99.91%
Evidence Level	L3
US Market Status	Not Marketed
Number of NDAs	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available in structured form (data gap). Based on the clinical evidence collected in this evidence pack, papaverine is well documented as a non-selective phosphodiesterase (PDE3/PDE4) inhibitor that relaxes vascular smooth muscle by raising intracellular cAMP/cGMP levels. Clinically, it has been used for decades as an intra-arterial and intraluminal vasodilator — for example, to prevent graft spasm during internal thoracic/radial artery harvesting in CABG, to treat non-occlusive mesenteric ischemia, and to measure coronary flow reserve during catheterization.

This existing vasodilatory / anti-vasospastic role is mechanistically consistent with the pathophysiology of ischemic disease, where impaired tissue perfusion due to vasospasm or reduced vascular flow reserve is a central feature. In this sense, the TxGNN prediction largely formalizes an already-established clinical practice pattern rather than proposing an entirely novel hypothesis — papaverine is already used as an adjunct in ischemia-related procedures, but rigorous therapeutic-endpoint trials specifically targeting “ischemic disease” as a formal indication remain limited.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT06014242	NA	Withdrawn	0	Peripheral microvascular resistance as a predictor of limb salvage in critical limb ischemia; withdrawn with no data.
NCT06795035	N/A	Recruiting	70	Coronary microvascular dysfunction after STEMI assessed via continuous saline thermodilution; papaverine relevant to CFR/microvascular resistance testing methodology.
NCT05562908	NA	Completed	165	Skeletonised vs. pedicled internal thoracic artery harvesting for CABG; papaverine used as standard intraoperative anti-spasm treatment.
NCT06125392	N/A	Recruiting	1000	Multicenter registry on chronic angina without obstructive coronary stenosis, seeking a new acetylcholine-spasm definition.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
3661361	1987	Cohort	American Heart Journal	Intracoronary papaverine superior to radiographic contrast for measuring coronary flow reserve in ischemic heart disease.
12964071	2003	Review	RoFo	Review of non-occlusive mesenteric ischemia; discusses vasodilator therapy including papaverine infusion.
7590571	1995	Review	Hepato-Gastroenterology	Non-occlusive mesenteric ischemia pathophysiology and vasodilator treatment approaches.
32713799	2020	Preclinical/Mechanistic	J Pharmacol Sci	Papaverine shows anti-inflammatory/immunomodulatory effects and reduces infarct volume in a mouse cerebral ischemia model.
28832798	2017	Preclinical	Braz J Cardiovasc Surg	Papaverine + ascorbic acid reduced liver injury from ischemia-reperfusion after aortic cross-clamping in rats.
16368347	2006	Not classified	Ann Thorac Surg	Compared papaverine vs. glyceryl-trinitrate/verapamil as topical/intraluminal vasodilators for internal thoracic artery spasm.
9972912	1998	Not classified	J Cardiovasc Surg	Intrathecal papaverine plus cooling extended safe aortic cross-clamping time via spinal cord protection in a porcine model.
831413	1977	Not classified	American Heart Journal	Compared papaverine and adenosine effects on myocardial blood flow during coronary reperfusion.
8293164	1993	Not classified	Current Opinion in Neurology	Reviews superselective intra-arterial papaverine infusion for cerebral vasospasm after aneurysm rupture.
9674923	1998	Not classified	Microsurgery	In vitro/in vivo comparison of lidocaine and papaverine vasodilation for flap ischemia prevention.

US Market Information

Currently not marketed — no authorization/license records were found for this drug in this jurisdiction (0 NDAs on file).

Safety Considerations

Please refer to the package insert for safety information.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Papaverine’s vasodilatory/anti-vasospastic mechanism is well documented and already used clinically as an adjunct in ischemia-related procedures (graft spasm prevention, mesenteric ischemia, coronary flow reserve testing), giving the TxGNN prediction reasonable mechanistic and observational support (L3). However, no dedicated Phase 2/3 RCT establishes papaverine as a primary therapy for “ischemic disease” as a standalone indication, and the drug currently has no marketing authorization in this jurisdiction.

To proceed, the following is needed:

Blocking gap (DG001): TFDA/local regulatory label warnings and contraindications must be obtained (e.g., via label PDF retrieval) before any S1 safety review can proceed.
High-priority gap (DG002): Formal mechanism-of-action documentation (e.g., from DrugBank API) to support mechanistic-link analysis.
Confirmation of route compatibility (currently marked “pending”) between required administration route for ischemic disease treatment and available formulations.
A dedicated interventional trial with ischemic disease as the primary efficacy endpoint, rather than papaverine’s current role as a diagnostic/procedural adjunct.
Disclaimer

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