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Inositol nicotinate API Manufacturers & Suppliers

General Description:

Inositol nicotinate, identified by CAS number 6556-11-2, is a notable compound with significant therapeutic applications. Inositol nicotinate, also known as Inositol hexaniacinate/hexanicotinate or "no-flush niacin", is a niacin ester and vasodilator. It is used in food supplements as a source of niacin (vitamin B3), where hydrolysis of 1 g (1.23 mmol) inositol hexanicotinate yields 0.91 g nicotinic acid and 0.22 g inositol. Niacin exists in different forms including nicotinic acid, nicotinamide and other derivatives such as inositol nicotinate. It is associated with reduced flushing compared to other vasodilators by being broken down into the metabolites and inositol at a slower rate. Nicotinic acid plays an essential role in many important metabolic processes and has been used as lipid-lowering agent. Inositol nicotinate is prescribed in Europe under the name Hexopal as a symptomatic treatment for severe intermittent claudication and Raynaud’s phenomenon.

Indications:

This drug is primarily indicated for: Indicated as a dietary supplement for the source of niacin. Has been investigated for potential beneficial effects on serum lipids. In Europe, inositol hexanicotinate is indicated as a patented drug known as Hexopal, which is therapeutically indicated for the symptomatic relief of severe intermittent claudication and Raynaud’s phenomenon. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Inositol nicotinate undergoes metabolic processing primarily in: Inositol nicotinate undergoes hydrolysis by plasma esterases, releasing free nicotinic acid and inositol in a sustained manner. The process takes more than 48hours, where the bloodstream enzymatic hydrolysis of inositol hexanicotinate was found to be slower in the first ester linkage of inositol hexanicotinate than in subsequent linkages . Sequential hydrolytic steps of inositol nicotinate forms one nicotinic acid molecule in each step, producing eventually six molecules of nicotinic acid and one inositol moiety . This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Inositol nicotinate are crucial for its therapeutic efficacy: Gastrointestinal absorption of inositol hexanicotinate varies widely, with an average of 70% of an orally ingested dose absorbed from stomach and upper small intestines into the bloodstream as intact form. The maximum serum levels of nicotinic acid is reached approximately 6-10 hours after oral ingestion. At low concentrations, the absorption of nicotinic acid and nicotinamide is mediated by sodium ion-dependent facilitated diffusion. At higher concentrations, passive diffusion predominates with doses of 3 to 4 g of niacin being almost completely absorbed . The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Inositol nicotinate is an important consideration for its dosing schedule: Mean elimination half life in healthy human adults is approximately one hour . This determines the duration of action and helps in formulating effective dosing regimens.

Route of Elimination:

The elimination of Inositol nicotinate from the body primarily occurs through: Unabsorbed inositol nicotinate is detected in feces. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Inositol nicotinate is distributed throughout the body with a volume of distribution of: Mean Vd following intravenous administration of 50mg/kg of inositol nicotinate in rats is 1051±250 mL/kg . This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Inositol nicotinate is a critical factor in determining its safe and effective dosage: Mean clearance rate following intravenous administration of 50mg/kg of inositol nicotinate in rats is 65.4±19 mL/min/kg . It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Inositol nicotinate exerts its therapeutic effects through: Inositol nicotinate mediates a vasodilatory, lipid-lowering and fibrinolytic effect on the cardiovascular system. Like other niacins, inositol nicotinate is a lipid-regulating agent that reduces the levels of plasma triglycerides, atherogenic apolipoprotein B (apoB)-containing lipoproteins (VLDL, LDL and lipoprotein a) while increasing antiatherogenic apoA-I-containing HDL levels . The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Inositol nicotinate functions by: Inositol nicotinate and other niacins directly and noncompetitively inhibit microsomal enzyme diacylglycerol acyltransferase 2 (DGAT2) responsible for esterification of fatty acids to form triglycerides, resulting in decreased triglyceride synthesis and hepatic atherogenic lipoprotein secretion. Inhibitied triglyceride synthesis results in accelerated intracellular hepatic apo B degradation and the decreased secretion of VLDL and LDL particles . Niacin also inhibits hepatic expression of beta-chain adenosine triphosphate synthase which inhibits the removal or uptake of HDL–apo A-I. It is also suggested that niacin increases vascular endothelial cell redox state, resulting in the inhibition of oxidative stress and vascular inflammatory genes or key cytokines involved in atherosclerosis. It acts as a ligand on G-protein coupled receptor 109A (HCAR2/HM74A) and 109B (HCAR3/HM74) which mediates the anti-lipolytic and lipid-lowering effects of nicotinic acid. Niacin-mediated signalling of GPR109A expressed on adipocytes and G(i)-mediated decrease in cAMP levels result in decreased lipolysis, fatty acid mobilization, and triglyceride synthesis. The action of inositol nicotinate on GPR109A expressed on skin and macrophages to cause increased prostaglandin D2/E2 activity is thought to be less significant compared to other niacin molecules as it involves sustained release that leads to less flushing . This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Inositol nicotinate belongs to the class of organic compounds known as hexacarboxylic acids and derivatives. These are carboxylic acids containing exactly six carboxyl groups, classified under the direct parent group Hexacarboxylic acids and derivatives. This compound is a part of the Organic compounds, falling under the Organic acids and derivatives superclass, and categorized within the Carboxylic acids and derivatives class, specifically within the Hexacarboxylic acids and derivatives subclass.

Categories:

Inositol nicotinate is categorized under the following therapeutic classes: Cardiovascular Agents, Nicotinic Acid and Derivatives, Other Nutritional Agents, Peripheral Vasodilators, Pyridines, Vasodilating Agents, Vitamin B Complex, Vitamins. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Inositol nicotinate include:

• Water Solubility: Insoluble