Isosorbide Mononitrate

證據等級: L5

預測適應症: 10 個

Isosorbide Mononitrate: A Nitrate Vasodilator Under Evaluation for Pulmonary Arterial Hypertension

One-Sentence Summary

Isosorbide mononitrate (ISMN, DB01020) has no Taiwan market license on file, and its original approved indication is not available in this Evidence Pack (data gap). TxGNN’s top-ranked predictions (hypertrichosis, alopecia, and several rare congenital syndromes) were reviewed and found to have no supporting mechanistic or literature evidence — most appear to be artifacts of disease-embedding clustering in the model. The one candidate with genuine, if preliminary, support is Pulmonary Arterial Hypertension (PAH), ranked #10 by TxGNN score but the only indication reaching evidence level L3 with 6 literature references and a coherent NO–sGC–cGMP mechanistic rationale.

Note on methodology deviation: This report deviates from mechanically reporting predicted_indications[0] (hypertrichosis) as the headline candidate. The evidence pack’s own rationale text for ranks 1–9 explicitly states there is “no clinical or preclinical evidence” and flags internal contradictions (e.g., near-identical high scores for both alopecia and hypertrichosis — opposite phenotypes). Presenting a Hold-recommendation, zero-evidence prediction as the lead finding would be misleading. PAH is used below as the substantive candidate for evaluation.

Quick Overview

Item	Content
Original Indication	Not available — TFDA has no market license on file for this drug (data gap, see DG001/DG002)
Predicted New Indication	Pulmonary Arterial Hypertension
TxGNN Prediction Score	99.94% (rank 10 of candidate list)
Evidence Level	L3
Taiwan Market Status	未上市 (Not marketed)
Number of Licenses	0
Recommended Decision	Hold (Research Question — hypothesis-generating, not yet clinically actionable)

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available (DG002, High severity — DrugBank MOA lookup pending). Based on known pharmacology reflected in the literature evidence itself, isosorbide mononitrate is a nitric oxide (NO) donor that acts through the NO–soluble guanylate cyclase (sGC)–cGMP signaling pathway to produce vasodilation.

This pathway is already a validated drug target in PAH: riociguat directly stimulates sGC, and sildenafil prolongs cGMP signaling by inhibiting its breakdown. One literature reference (PMID 29705351) directly examined NO-sensitive sGC stimulation in a monocrotaline-induced pulmonary hypertension rat model, and another (PMID 29377691) describes a novel hybrid molecule synthesized from ISMN itself that produced pulmonary vasodilation and reduced vascular remodeling in PAH rats. This gives the ISMN→PAH hypothesis a concrete mechanistic anchor, unlike the hair-disorder predictions.

However, the rationale also flags a known limitation: chronic nitrate use is associated with pharmacological tolerance and reflex tachycardia, and no clinical trial has tested ISMN directly in PAH patients. The supporting literature is a mix of drug-design, preclinical, and tangentially related clinical studies (several concern cirrhosis-related portal hypertension or coronary artery disease, not PAH) — so this remains a research hypothesis rather than a clinically supported repurposing case.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
29377691	2018	Drug design/synthesis	Journal of Medicinal Chemistry	Novel hybrid synthesized from ISMN + bardoxolone methyl lowered mean pulmonary artery pressure and right ventricular systolic pressure, with dual vasodilation and anti-remodeling activity in PAH rats
29705351	2018	Preclinical/Animal model	Life Sciences	Examined NO-sensitive soluble guanylate cyclase stimulation in monocrotaline-induced pulmonary hypertension rats, supporting the NO-sGC pathway as a target for halting PH progression
3384359	1988	Review/Pharmacology	Gut	Oral ISMN reduced portal pressure via decreased portal venous resistance in cirrhotic patients with portal hypertension (hepatic, not pulmonary, vasculature)
16422873	2005	Clinical (CAD, not PAH)	Journal of Sexual Medicine	Hemodynamic study of sildenafil plus ISMN in coronary artery disease patients with erectile dysfunction; not a PAH population
2759546	1989	Clinical (cirrhosis, unrelated)	Hepatology	Randomized study found ISMN had no significant effect on hepatic hemodynamics in HBsAg-positive cirrhosis — a negative finding, unrelated to PAH
9673832	1998	Review	Clinical Pharmacokinetics	General pharmacokinetic review of vasodilator classes including nitrates; background context only

Taiwan Market Information

No licensing records are available — this drug currently has 0 approved licenses and market status “未上市” (not marketed) in Taiwan.

Safety Considerations

Please refer to the package insert for safety information. (Key warnings, contraindications, and drug interaction data are flagged as a Blocking data gap — DG001 — pending TFDA package insert retrieval; this must be resolved before any S1 safety assessment can proceed.)

Conclusion and Next Steps

Decision: Hold

Rationale: The PAH hypothesis has a coherent mechanistic basis (NO–sGC–cGMP pathway, an established PAH drug target) and preclinical/drug-design support, but no clinical trial has tested ISMN in PAH patients, and the drug is unmarketed in Taiwan with no available safety labeling. The other nine TxGNN-ranked predictions (hypertrichosis, alopecia, and several rare syndromes) lack any supporting evidence and should not be pursued further — they are most plausibly artifacts of disease-embedding proximity in the model.

To proceed, the following is needed:

TFDA package insert / warnings and contraindications (DG001, Blocking)
Confirmed mechanism of action from DrugBank (DG002, High)
A dedicated preclinical or early-phase clinical study of ISMN specifically in PAH populations
Clarification of Taiwan/global regulatory status, since this drug currently has no Taiwan market license
Disclaimer

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