Acipimox

Methylpyrazine-2- Acipimox Anti-lipolytic Oxidation Pseudomonas putida Single-stage fermentation [6]... 

Acipimox (5) was introduced in Europe to treat hyperlipidemia in 1985 [47,48]. Acipimox is a weak agonist of GPR109A with micromolar binding and functional activity. Like niacin, acipimox raises HDL-C and triggers vasodilation in humans. However, it remains unclear whether acipimox causes mild hyperglycemia as is observed with niacin [49,50]. 

Nicotinic acid and its derivatives (pyridylcarbinol, xanthinol nicotinate, acipimox) activate endothelial lipoprotein lipase and thereby lower triglyceride levels. At the start of therapy, a prostaglandin-mediated vasodilation occurs (flushing and hypotension) that can be prevented by low doses of acetyl-salicylic acid. 

Nicotinic acid (5.18), and related derivatives such as pyridylcarbinol (5.19), xanthinol nicotinate (5.20), acipimox (5.21), given in large doses, influence the lipoprotein ratio, decreasing the concentrations of very low and low-density lipoprotein, but have no effect on HDL-cholesterol complexes. Acipimox (5.21) is a new pyrazine derivative that is 20 times more active than nicotinic acid. When first administered, the use of these agents is associated with flushing and hypotension. 

In an open study, blood glucose was on average slightly lowered in 3009 type II diabetics given acipimox for at least 2 months (3). 

Yeshurun D, Hamood H, Morad N, Naschitz J. [Acipimox (Olbetam) as a secondary hypolipemic agent in combined hypertriglyceridemia and hyperlipidemia.JHarefuah 2000 138(8) 650-3710. 

Lavezzari M, Milanesi G, Oggioni E, Pamparana F. Results of a phase IV study carried out with acipimox in type II diabetic patients with concomitant hyperlipoproteinaemia. J Int Med Res 1989 17(4) 373-80. 

Nicotinic acid derivatives include acipimox, aluminium nicotinate, nicotinyl alcohol, and xanthinol nicotinate. The adverse effects of these compounds appear to be identical to those of nicotinic acid. 

Acipimox had to be withdrawn in 10 of 32 patients with hypertriglyceridemia, excessive hypertriglyceridemia, and combined hyperlipidemia because of adverse effects or absence of clinical response (15). The other 22 completed... 

---