单硝酸异山梨酯, Isosorbide 5-mononitrate

1,4:3,6-Dianhydro-5-nitro-D-glucitol

Isosorbide mononitrate (ISMN) is a nitric oxide (NO) donor with cardioprotective activity. It induces relaxation of precontracted isolated rat mesenteric artery rings with and without endothelium (EC50s = 87 and 30.1 µM, respectively). ISMN (150 mg/kg) prevents increases in blood pressure and plasma levels of thromboxane A2 (TXA2), as well as reduces platelet aggregation in a rat model of hypertension induced by cyclosporin A (CsA;) when administered prior to CsA. However, ISMN exacerbates the CsA-induced cardiac phenotype in rats when administered seven weeks after initial CsA administration. ISMN (200 mg/kg) decreases aortic superoxide production, reduces intima-media thickness of the thoracic aorta, and improves endothelium-dependent vasorelaxation in a rabbit model of cholesterol-enriched diet-induced atherosclerosis. It also prolongs survival time of mice in a normobaric hypoxia test. Formulations containing ISMN have been used in the treatment of angina in patients with coronary artery disease.

Isosorbide Mononitrate is the mononitrate salt form of isosorbide, an organic nitrate with vasodilator activity. Isosorbide mononitrate relaxes vascular smooth muscle by formation of the free radical nitric oxide (NO), which is identical to the endothelium-derived relaxing factor (EDRF). NO activates guanylyl cyclase, thereby increasing the synthesis of cGMP within smooth muscle, resulting in dephosphorylation of light chain myosin and relaxation of peripheral arteries and veins. In addition, isosorbide mononitrate relaxes coronary arteries, thereby increasing the blood circulation through the ischemic area. (NCI05)

Isosorbide mononitrate, also known as mononit or ismo, belongs to the class of organic compounds known as isosorbides. These are organic polycyclic compounds containing an isosorbide(1, 4-Dianhydrosorbitol) moiety, which consists of two -oxolan-3-ol rings. Isosorbide mononitrate is a drug which is used for the prevention of angina pectoris due to coronary artery disease and the treatment of acute and chronic angina pectoris, hypertension, and myocardial infarction. Isosorbide mononitrate exists as a solid, soluble (in water), and a very weakly acidic compound (based on its pKa). Isosorbide mononitrate has been detected in multiple biofluids, such as urine and blood. Within the cell, isosorbide mononitrate is primarily located in the cytoplasm.

Isosorbide mononitrate is a nitrate ester and a glucitol derivative. It has a role as a nitric oxide donor and a vasodilator agent.

Isosorbide is a naturally occurring sugar alcohol (polyol) that is found in small quantities in many plants and fruits. It is used as a pharmaceutical drug to treat angina pectoris, congestive heart failure, and high blood pressure. Isosorbide has been shown to inhibit the activity of matrix metalloproteinases (MMPs), which are enzymes that degrade extracellular matrix proteins. This effect may be beneficial for patients with disorders such as arthritis. Isosorbide also increases nitric oxide production, leading to vasodilation and improved blood flow. The therapeutic effect of isosorbide has been demonstrated in experimental models using mice with congestive heart failure due to myocardial infarction or chronic heart disease. Pharmacological treatment of these animals with isosorbide resulted in an improvement of left ventricular function, reduction of myocardial fibrosis, and reduced levels of cardiac markers.

Title: Isosorbide Dinitrate

CAS Registry Number: 87-33-2

CAS Name: 1,4:3,6-Dianhydro-D-glucitol dinitrate

Additional Names: dinitrosorbide; 1,4:3,6-dianhydrosorbitol 2,5-dinitrate

Trademarks: Carvasin (Teofarma); Cedocard (Pharmacia); Corovliss (Roche); Dignonitrat (Sankyo); Dilatrate (Schwarz); Diniket (Schwarz); Frandol (Toa Eiyo); Imtack (AstraZeneca); Isocard (Schwarz); Isoket (Schwarz); IsoMack (Mack, Illert.); Isorbid (Wyeth); Isordil (Wyeth); Isostenase (Azupharma); Isotrate (Warner-Chilcott); Langoran (Aventis); Maycor (Parke-Davis); Myorexon (AstraZeneca); Nitorol (Eisai); Nitrol (Altana); Nitrosorbon (Pohl); Rifloc (Avensa); Risordan (Aventis); Sorbangil (Pharmacia); Sorbichew (AstraZeneca); Sorbidilat (AstraZeneca); Sorbid SA (AstraZeneca); Sorbitrate (AstraZeneca); Vascardin (Roche); Vasorbate (Roche)

Molecular Formula: C6H8N2O8

Molecular Weight: 236.14

Percent Composition: C 30.52%, H 3.41%, N 11.86%, O 54.20%

Literature References: Coronary vasodilator. Prepn from sorbitol: Goldberg, Acta Physiol. Scand. 15, 173 (1948), C.A. 42, 5564 (1948); Kochergin, Titkova, C.A. 54, 8647h (1960). Absorption and disposition in man: H. Laufen et al., Arzneim.-Forsch. 33, 980 (1983). Comprehensive description: L. A. Silvieri, N. J. DeAngelis, Anal. Profiles Drug Subs. 4, 225-244 (1975).

Properties: Hard colorless crystals, mp 70°. [a]D20 +135° (alc). Sparingly sol in water (1.089 mg/ml, also given as 1.0 g dissolves in 900 ml H2O). Freely sol in organic solvents, such as acetone, alc, ether.

Melting point: mp 70°

Optical Rotation: [a]D20 +135° (alc)

Derivative Type: Isosorbide-5-mononitrate

CAS Registry Number: 16051-77-7

Trademarks: Corangin (Novartis); Elan (Schwarz); Elantan (Schwarz); Imdur (Key); Ismo (Roche); Isomonat (Roche); Monicor (Fabre); Monit (Lorex); Mono-Cedocard (Altana); Monoclair (Hennig); Monoket (Schwarz); Mono Mack (Mack, Illert.); Monosorb (Dexcel); Olicard (Solvay); Pentacard (Cedona)

Molecular Formula: C6H9NO6

Molecular Weight: 191.14

Percent Composition: C 37.70%, H 4.75%, N 7.33%, O 50.22%

Literature References: Metabolite of isosorbide dinitrate.

 Therap-Cat: Antianginal.

Keywords: Antianginal.