Repositioning Candidate Details
| Candidate ID: | R0373 |
| Source ID: | DB01020 |
| Source Type: | approved |
| Compound Type: | small molecule |
| Compound Name: | Isosorbide mononitrate |
| Synonyms: | IS 5-MN; IS-5-MN; IS-5MN; ISMN; Iso-5-mononitrate; Isosorbide 5-mononitrate; Isosorbide 5-nitrate; Isosorbide mononitrate; Isosorbide-5-mononitrate; Monosorbitrate |
| Molecular Formula: | C6H9NO6 |
| SMILES: | [H][C@]12OC[C@@H](O[N+]([O-])=O)[C@@]1([H])OC[C@@H]2O |
| Structure: |
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| DrugBank Description: | Isosorbide mononitrate is an organic nitrate with vasodilating properties. It is an anti-anginal agent that works by relaxing the smooth muscles of both arteries and veins, but but predominantly veins to reduce cardiac preload. Isosorbide mononitrate is an active metabolite of . Like other organic nitrates, isosorbide mononitrate acts as a prodrug for its active metabolite, , which mediates the therapeutic action of isosorbide mononitrate. Isosorbide mononitrate has a longer duration of action than due to its slow onset of absorption and metabolism. First approved by the FDA in 1991, isosorbide mononitrate is used for the prevention and management of angina pectoris caused by coronary artery disease; however, the onset of action of orally-administered isosorbide mononitrate is not rapid enough to offset an acute anginal episode. It is available in oral tablets generically and under the brand name ISMO and Monoket. The extended-release forms of the drug are also available generically and under the brand name Imdur. |
| CAS Number: | 16051-77-7 |
| Molecular Weight: | 191.1388 |
| DrugBank Indication: | Isosorbide mononitrate is indicated for the prevention and management of angina pectoris due to coronary artery disease. The onset of action of oral isosorbide mononitrate is not sufficiently rapid to be useful in aborting an acute anginal episode. |
| DrugBank Pharmacology: | Isosorbide mononitrate is an anti-anginal agent and vasodilator that relaxes vascular smooth muscle to prevent and manage angina pectoris. The pharmacological action is mediated by the active metabolite, , which is released when isosorbide mononitrate is metabolized. Nitric oxide works on both arteries and veins, but predominantly veins: by relaxing veins and reducing the central venous pressure, nitric oxide causes venous pooling and a decrease in the venous return to the heart, thus decreasing cardiac preload. In healthy subjects, the stroke volume is decreased and venous pooling can occur in the standing posture, leading to postural hypotension and dizziness. At therapeutic doses of isosorbide mononitrate, nitric oxide has a bigger effect on larger muscular arteries over small resistance arteries. Arterial relaxation leads to reduced systemic vascular resistance and systolic blood (aortic) pressure, decreasing to decreased cardiac afterload. The direct dilator effect on coronary arteries opposes the coronary artery spasm in variant angina or angina pectoris. At larger doses, nitric oxide causes the resistance arteries and arterioles to dilate, reducing arterial pressure via coronary vasodilatation. This leads to increased coronary blood flow. Reduced cardiac preload and afterload caused by nitric oxide causes a reduction in myocardial oxygen consumption; decreased myocardial oxygen demand, along with increased coronary blood flow, leads to an increased in the oxygen content of coronary sinus blood and the relief from ischemia. The end effect of isosorbide mononitrate include decreased cardiac oxygen consumption, redistribution coronary flow toward ischemic areas via collaterals, and the relief of coronary spasms. Nitric oxide can also increase the rate of relaxation of cardiac muscles, which is an effect outside of vascular smooth muscles. Organic nitrates can also relax other types of smooth muscles, including esophageal and biliary smooth muscle. The anti-anginal activity of isosorbide mononitrate was observed about 1 hour after dosing, and the peak effect was achieved from 1-4 hours after dosing. The duration of anti-anginal action of at least 12 hours was observed with an asymmetrical dosing regimen. |
| DrugBank MoA: | Isosorbide mononitrate acts as a prodrug for nitric oxide (NO), which is a potent vasodilator gas that is released when the drug is metabolized. NO activates soluble guanylyl cyclase in vascular endothelial cells, which increases the intracellular concentrations of cyclic GMP (cGMP). cGMP activates cGMP-dependent protein kinases, such as protein kinase G and I, which activates the downstream intracellular cascades. The downstream cascade results in reduced intracellular concentrations of calcium, caused by processes including inhibition of IP<sub>3</sub>-mediated pathway, phosphorylation of big calcium-activated potassium channel leading to cell hyperpolarization and reduced calcium influx, and increased calcium efflux via the Ca2+-ATPase-pump. Reduced intracellular calcium concentrations lead to the dephosphorylation of myosin light chains and the relaxation of smooth muscle cells. |
| Targets: | Guanylate cyclase soluble subunit alpha-2 activator |
| Inclusion Criteria: | Indication associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
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| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
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| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I08 | 114 | Cardiovascular system disease | A disease of anatomical entity which occurs in the blood, heart, blood vessels or the lymphatic system that passes nutrients (such as amino acids and electrolytes), gases, hormones, blood cells or lymph to and from cells in the body to help fight diseases and help stabilize body temperature and pH to maintain homeostasis. http://en.wikipedia.org/wiki/Circulatory_system | disease of anatomical entity | Details |
| I16 | 6713 | Cerebrovascular disease | An vascular disease that is characterized by dysfunction of the blood vessels supplying the brain. http://en.wikipedia.org/wiki/Cerebrovascular_disease, http://www.ncbi.nlm.nih.gov/books/NBK378/ | disease of anatomical entity/ cardiovascular system disease/ vascular disease/cerebrovascular disease | Details |