Pentaerythritol tetranitrate API Manufacturers

General Description:

Pentaerythritol tetranitrate, identified by CAS number 78-11-5, is a notable compound with significant therapeutic applications. 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 .

Indications:

This drug is primarily indicated for: Used for the treatment of angina pectoris . Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Pentaerythritol tetranitrate undergoes metabolic processing primarily in: Extensively metabolized in the liver . Metabolites: pentaerythritol trinitrate, pentaerythritol dinitrate, pentaerythritol mononitrate, & pentaerythritol (inactive). This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Half-life:

The half-life of Pentaerythritol tetranitrate is an important consideration for its dosing schedule: The elimination half-life in plasma from male volunteers given an oral 100-mg dose of the tetranitrate was reported to be 4-5 hours . This determines the duration of action and helps in formulating effective dosing regimens.

Route of Elimination:

The elimination of Pentaerythritol tetranitrate from the body primarily occurs through: Mainly the urine . Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Pentaerythritol tetranitrate is distributed throughout the body with a volume of distribution of: The steady-state volume of distribution was 4.2 +/- 1.1 L/kg (n = 6) in rats given this drug by the intra-arterial route . This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Pentaerythritol tetranitrate is a critical factor in determining its safe and effective dosage: In a pharmacokinetic study of rats after intra-arterial administration of this drug, the clearance was measured to be 0.61 +/- 0.16 L/min/kg . It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Pentaerythritol tetranitrate exerts its therapeutic effects through: 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 . The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Pentaerythritol tetranitrate functions by: 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 . This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Pentaerythritol tetranitrate belongs to the class of organic compounds known as alkyl nitrates. These are organic compounds containing a nitrate that is O-linked to an alkyl group, classified under the direct parent group Alkyl nitrates. This compound is a part of the Organic compounds, falling under the Organic oxygen compounds superclass, and categorized within the Organic oxoanionic compounds class, specifically within the Organic nitrates subclass.

Categories:

Pentaerythritol tetranitrate is categorized under the following therapeutic classes: Alcohols, Antianginal Agents, Carbohydrates, Cardiac Therapy, Cardiovascular Agents, Drugs that are Mainly Renally Excreted, Fibrin Modulating Agents, Glycols, Hematologic Agents, Organic Nitrates, Polysaccharides, Propylene Glycols, Vasodilating Agents, Vasodilators Used in Cardiac Diseases. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Pentaerythritol tetranitrate include:

• Water Solubility: 0.133 mg/mL
• Melting Point: 140