Inositol nicotinate

Originator

Hexanicotol,Philadelphia,US,1962

Uses

benzidine substitute

Uses

myo-Inositol Hexanicotinate is an nicotinate conjugate of myo-inositol, an structural basis for a number of secondary messengers.

Definition

ChEBI: Inositol hexanicotinate is an inositol nicotinate. It is functionally related to a nicotinic acid.

Manufacturing Process

100 g of nicotinic acid were suspended in 265 ml of distilled and dried pyridine without stirring. 68 g of phosphorus oxychloride were added dropwise to this mixture under continual stirring. The temperature of the reactants, initially at 20°C, was allowed to rise to about 60°C, and this temperature was maintained for a further 60 minutes. Thereafter 24.5 g of meso-inositol wereadded gradually, the temperature being controlled so that it did not exceed about 80°C. The reactants were maintained at this temperature for from 2 to 3 hours, and thereafter the reaction mixture was poured into 500 ml of water. The pyridine salts formed during the reaction readily dissolved, and the mesoinositol hexanicotinate which had formed crystallized out. The ester was filtered off and washed with water and acetone or alcohol. Finally, the mesoinositol hexanicotinate was dried at 100°C.
The yield was 90%, the melting point of the product was 258°C to 260°C. and the chlorine content <0.01%.

brand name

Hexopal (Sterling Winthrop); Linodil (Sterling Winthrop); Palohex (Sterling Winthrop).

Therapeutic Function

Vasodilator

Clinical Use

Peripheral vascular disease

Hyperlipidaemia

Synthesis

Inositol nicotinate is obtained by mechanochemical esterification under high-speed ball-milling at room temperature, run solvent-free with I2/KH2PO2 or KI/P(OEt)3, and the I2/KH2PO2 route gives the product in moderate yield without column chromatography[1].

Drug interactions

Potentially hazardous interactions with other drugs
Statins: increased risk of myopathy.

Metabolism

Inositol nicotinate is believed to be slowly hydrolysed to nicotinic acid. The main route of metabolism is then conversion to N-methylnicotinamide and the 2-pyridone and 4-pyridone derivatives; nicotinuric acid is also formed.
Small amounts of nicotinic acid are excreted unchanged in urine.

References

[1] Zheng, L., Sun, C., Xu, W., Dushkin, A. V., Polyakov, N., Su, W., Yu, J. (2021). Mechanically induced solvent-free esterification method at room temperature. RSC Advances, 11(9), 5080–5085. https://doi.org/10.1039/d0ra09437d