General Description
ISOSORBIDE-5-MONONITRATE(16051-77-7) is a crystalline solid. ISOSORBIDE-5-MONONITRATE(16051-77-7) is very flammable and may be toxic by ingestion.
Reactivity Profile
The dinitrate, a heart drug, can detonate when dry, but is non explosive with 30% of water [J. Haz.. Mater., 1992, 32(1), 87]. The mononitrate would be expected to be less reactive.
Air & Water Reactions
Highly flammable.
Health Hazard
Fire may produce irritating and/or toxic gases. Contact may cause burns to skin and eyes. Contact with molten substance may cause severe burns to skin and eyes. Runoff from fire control may cause pollution.
Fire Hazard
Flammable/combustible material. May be ignited by friction, heat, sparks or flames. Some may burn rapidly with flare burning effect. Powders, dusts, shavings, borings, turnings or cuttings may explode or burn with explosive violence. Substance may be transported in a molten form at a temperature that may be above its flash point. May re-ignite after fire is extinguished.
Chemical Properties
white to light yellow crystal powde
Uses
A metabolite of Isosorbide Dinitrate. Used as an antianginal
Uses
antidepressant, 5HT reuptake inhibitor
Definition
ChEBI: Isosorbide mononitrate is a nitrate ester and a glucitol derivative. It has a role as a nitric oxide donor and a vasodilator agent.
Brand name
Imdur (Schering-Plough); Ismo (Dr. Reddy’s);
Monoket (Schwarz Pharma)
.
Clinical Use
Vasodilator:
Treatment and prophylaxis of angina
Adjunct in congestive heart failure
Synthesis
The general procedure for the synthesis of isosorbide 2-nitrate from isosorbide (stored below +4°C) is as follows: 146 g of dehydrated sorbitol was dissolved in 880 mL of anhydrous ethyl acetate, stirred well, and then cooled to -5 to 0°C. Subsequently, 170 g of silver nitrate solids were added, stirring was continued, and 120 g of thionyl chloride was added dropwise at a slow rate. After the dropwise addition was completed, the reaction mixture was stirred at the same temperature for 10 hours. Upon completion of the reaction, the reaction process was monitored by high performance liquid chromatography (HPLC). The reaction solution was filtered by suction filtration. The filtrate was washed to neutrality with 500 mL of water to purify the product. The organic phase was dried with 20 g of anhydrous magnesium sulfate for 4 hours. After drying, the magnesium sulfate was removed by filtration and the filtrate was decolorized by adding 17.6 g of activated carbon and heated to reflux for 30 minutes. After the decolorization was completed, the activated carbon was removed by filtration and the filtrate was concentrated to dryness by decompression to give 170 g of isosorbide 2-nitrate solid. The purity of the product was 99.85% and the yield was 89.0% by HPLC analysis.
Drug interactions
Potentially hazardous interactions with other drugs
Avanafil: hypotensive effect significantly enhanced -
avoid.
Levosimendan: possible severe hypotension.
Riociguat: avoid concomitant use due to risk of
hypotension.
Sildenafil: hypotensive effect significantly enhanced
- avoid.
Tadalafil: hypotensive effect significantly enhanced
- avoid.
Vardenafil: hypotensive effect significantly enhanced
- avoid.
Metabolism
Unlike isosorbide dinitrate, isosorbide mononitrate does
not undergo first-pass hepatic metabolism. Isosorbide
mononitrate is taken up by smooth muscle cells of blood
vessels and the nitrate group is cleaved to inorganic
nitrite and then to nitric oxide. Isosorbide mononitrate is
metabolised to inactive metabolites, including isosorbide
and isosorbide glucuronide
References
[1] Patent: CN107011354, 2017, A. Location in patent: Paragraph 0042-0057
[2] Journal of the Chemical Society, Perkin Transactions 1, 2000, # 12, p. 1809 - 1810
[3] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1997, vol. 36, # 9, p. 793 - 795
[4] ChemMedChem, 2015, vol. 10, # 10, p. 1724 - 1732
