| Candidate ID: | R0933 |
| Source ID: | DB06154 |
| Source Type: | approved |
| Compound Type: |
small molecule
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| Compound Name: |
Pentaerythritol tetranitrate
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| Synonyms: |
Corpent; PENT; PENTA; Pentaerithrityl tetranitrate; Pentaerythritol tetranitrate; Penthrite; TEN
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| Molecular Formula: |
C5H8N4O12
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| SMILES: |
[O-][N+](=O)OCC(CO[N+]([O-])=O)(CO[N+]([O-])=O)CO[N+]([O-])=O
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| Structure: |
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| DrugBank Description: |
Pentaerythritol tetranitrate is the nitrate ester of pentaerythritol that possesses explosive properties. When mixed with a plasticizer, this chemical forms a plastic explosive. It is recognized by the FDA to be a coronary vasodilator in the treatment of heart conditions such as angina .
It is a pentaerythritol nitrate in which all four hydroxy groups of pentaerythritol have been converted to the corresponding nitrate ester. It is a vasodilator with properties that are quite similar to those of glyceryl trinitrate, however, with a more prolonged duration of action. It is also one of the most powerful high explosives known and is a component of the plastic explosive known as Semtex .
PETN has the chemical formula C5H8N4O12. It is formed by reacting pentaerythritol (C5H12O4), an alcohol commonly used in paints and varnishes, with nitric acid (HNO2). The reacting solution is chilled to precipitate the PETN. It is then filtered out, washed, dried, and recrystallized to produce a colorless crystalline material that is stored and shipped as a mixture with water and alcohol .
Interestingly, this drug was studied for potential benefits in chronic ischemic heart failure patients. PETN targeting reactive oxygen species generation halted the changes of mitochondrial antioxidant enzymes and progressive fibrotic remodeling, leading to amelioration of cardiac functional performance in rats with ischemic heart failure .
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| CAS Number: |
78-11-5
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| Molecular Weight: |
316.1366
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| DrugBank Indication: |
Used for the treatment of angina pectoris .
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| DrugBank Pharmacology: |
Organic nitrate which causes systemic vasodilation, decreasing cardiovascular preload .
Nitrate enters vascular smooth muscle and converted to nitric oxide (NO) which acts as a cellular messenger, leading to activation of cyclic GMP and, therefore, vasodilation .
The nitrovasodilator group of drugs relaxes most smooth muscles in the body, including those in the walls of arteries and veins, and selectively dilate large coronary vessels . Lower doses of nitrates increase coronary blood flow without significantly affecting systemic arterial pressure. Higher doses, especially if repeated frequently, decrease systolic and diastolic blood pressure as well as cardiac output, which can result in a headache, weakness, dizziness, and the activation of compensatory sympathetic reflexes, including tachycardia and peripheral arteriolar vasoconstriction .
Smooth muscles in the bronchi, biliary tract, gastrointestinal tract, ureters, and uterus also can be relaxed by nitrovasodilators. PETN seems to be unique among the long-acting nitrovasodilators in that patients do not demonstrate tolerance to treatment, which results in sustained vasodilation in humans with continuous PETN treatment .
Important to note is that this drug is devoid of induction of oxidative stress and related side-effects such as endothelial dysfunction or tolerance to nitrates. Some of these effects are related to special pharmacokinetics of PETN, but upon chronic administration, PETN also induces antioxidative pathways at the genomic level, resulting in increased expression of heme _oxygenase-1 (HO-1)_ _and ferritin_, both possessing highly protective properties. There is good experimental evidence that at least part of the beneficial profile of long-term treatment with this drug is based on the activation of the _heme oxygenase-1/ferritin_ system .
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| DrugBank MoA: |
Pentaerythritol tetranitrate is the lipid soluble polyol ester of nitric acid belonging to the family of _nitro-vasodilators_. Pentaerythritol tetranitrate releases free nitric oxide (NO) after the denitration reaction, which triggers NO-dependent signaling transduction involving soluble _guanylate cyclase (sGC_). Nitric oxide binds reversibly to the ferrous-heme center of sGC, causing conformational change and activating the enzyme. This enzyme activation results in increased cellular concentrations of _cyclic guanosine monophosphate _(cGMP) within the vascular smooth muscle, resulting in vasodilation mediated by cGMP-dependent protein kinases. Additionally, this agent causes dose-dependent arterial and venous bed .
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| Targets: |
Hemoglobin subunit alpha agonist; Hemoglobin subunit beta agonist; Free radicals antagonist
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| Inclusion Criteria: |
Therapeutic strategy associated
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