S-Nitrosoglutathione

Summary

S-Nitrosoglutathione (GSNO) is an endogenous, naturally occurring S-nitrosothiol formed from glutathione and nitric oxide. It serves as a physiological NO reservoir and signaling molecule. Investigational uses include pulmonary hypertension, neonatal hypoxic respiratory failure, bronchopulmonary dysplasia, and topical wound healing. It has been studied in inhaled and intravenous formulations.

Mechanism of Action

Endogenous S-nitrosothiol that releases nitric oxide (NO) and transfers nitroso groups via transnitrosation reactions, activating soluble guanylate cyclase, increasing cGMP, causing smooth muscle relaxation, vasodilation, platelet inhibition, and bronchodilation.

Routes of Administration

Goals & Uses

• Pulmonary vasodilation in persistent pulmonary hypertension of the newborn (PPHN)Cardiovascular / PulmonaryModerate
• Systemic vasodilation in hypertensive crisisCardiovascularLow
• Wound healingDermatologicLowTissue repair and wound healing
• Bronchodilation / airway relaxationPulmonaryModerate
• Platelet inhibition / antithrombotic effectHematologyModerate

Contraindications

• Phosphodiesterase-5 inhibitor use (e.g., sildenafil)Drug InteractionHigh
• Methemoglobinemia or glucose-6-phosphate dehydrogenase deficiencyHematologicModerate
• Severe hypotensionCardiovascularHigh

Adverse Effects

• Tachycardia (reflex)CardiovascularUncommon
• MethemoglobinemiaHematologicUncommon
• HeadacheNeurologicCommonPain in the head or upper neck
• HypotensionCardiovascularCommonLow blood pressure
• FlushingVascularCommonWarmth and redness of the skin

Drug Interactions

• Sildenafil / PDE5 inhibitorsHigh
• GSNO reductase (GSNOR) inhibitorsModerate
• Antihypertensive agentsModerate
• Antiplatelet agents / anticoagulantsModerate

Population Constraints

• Premature neonatesPediatricRelative
• Pregnant womenReproductiveRelative
• Patients with renal or hepatic impairmentOrgan FunctionRelative

Regulatory Status

• European UnionInvestigationalNo EMA marketing authorization; evaluated in academic and early-phase clinical trials.
• United StatesInvestigationalStudied under IND for PPHN and pulmonary hypertension; no FDA approval as of 2024. Orphan drug status sought for neonatal indications.
• United KingdomInvestigationalNo MHRA approval; research-stage use only.

No approved therapeutic formulation in any major jurisdiction as of 2024. Investigated under IND in the US for pulmonary hypertension of the newborn and other vascular indications. SNAP Bioscience and other groups have developed GSNO-based drug candidates. Orphan drug designations have been pursued for neonatal indications.

Evidence & Sources

No sources recorded yet.