Isosorbide dinitrate, 硝酸异山梨酯

Isosorbide dinitrate is an organic nitrate ester and nitric oxide (NO) donor in the same class as nitroglycerin. It induces vasodilation with IC50 values of 0.56 and 1.82 µM for isolated precontracted rabbit femoral vein and artery, respectively. Isosorbide dinitrate increases oxygenation of tumor tissue in vivo in a mouse xenograft model. It also inhibits platelet aggregation in vitro and in vivo at concentrations in the micromolar range. Formulations containing isosorbide dinitrate have been used for the treatment of angina pectoris.

Coronary vasodilator.

Isosorbide Dinitrate is the dinitrate salt form of isosorbide, an organic nitrate with vasodilator activity. Isosorbide dinitrate 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 dinitrate relaxes coronary arteries, thereby increasing the blood circulation through the ischemic area. (NCI05)

Isosorbide dinitrate, also known as isoket or isordil, 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 dinitrate is a drug which is used for the prevention of angina pectoris due to coronary artery disease. Isosorbide dinitrate exists as a solid and is considered to be practically insoluble (in water) and relatively neutral. Isosorbide dinitrate has been detected in multiple biofluids, such as urine and blood. Within the cell, isosorbide dinitrate is primarily located in the membrane (predicted from logP).

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

Isosorbide dinitrate is used to treat chronic bronchitis and congestive heart failure. It dilates blood vessels, allowing more oxygen-rich blood to reach the heart. Isosorbide dinitrate is also used to relieve chest pain (angina) and reduce complications after a heart attack. Isosorbide dinitrate is a prodrug that is converted in vivo to its active form, isosorbide mononitrate, by the enzyme nitric oxide synthase in response to hypoxia. In addition, it has been shown that this drug reduces levels of low-density lipoprotein cholesterol (LDL-C) and may be useful for the treatment of high cholesterol. The mechanism of action for reducing LDL-C levels is not known but may be due to increased clearance of LDL-C from plasma or decreased production of very low density lipoproteins (VLDL).

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.