Nicotinic acid: an old drug with a promising future

Abstract

Nicotinic acid has been used for decades to treat dyslipidaemic states. In particular its ability to raise the plasma HDL cholesterol concentration has led to an increased interest in its pharmacological potential. The clinical use of nicotinic acid is somewhat limited due to several harmless but unpleasant side effects, most notably a cutaneous flushing phenomenon. With the recent discovery of a nicotinic acid receptor, it has become possible to better understand the mechanisms underlying the metabolic and vascular effects of nicotinic acid. Based on these new insights into the action of nicotinic acid, novel strategies are currently under development to maximize the pharmacological potential of this drug. The generation of both flushreducing co-medications of nicotinic acid and novel drugs targeting the nicotinic acid receptor will provide future therapeutic options for the treatment of dyslipidaemic disorders.

Niacin and biosynthesis of PGD2 by platelet COX-1 in mice and humans

“…Niacin is currently the only approved treatment for dyslipidemia that not only decreases LDL cholesterol, but also elevates HDL cholesterol (47). While the mechanism by which niacin influences HDL remains unclear, it appears to be independent of its activation of GPR109A (47).…”

“…While the mechanism by which niacin influences HDL remains unclear, it appears to be independent of its activation of GPR109A (47). Formation of COX-1-dependent PGD 2 and PGE 2 by cutaneous dendritic cells, followed by COX-2-dependent formation of PGE 2 by keratinocytes, results in flushing via activation of vascular DP1, EP2, and EP4 receptors (24), an adverse effect of niacin that compromises patient adherence (47). Niacin-dependent activation of GPR109A also restrains atherogenesis in mice, independent of its effects on lipids, by inducing ABCG1-dependent macrophage cholesterol efflux and inhibiting MIP-1-dependent macrophage recruitment to the vasculature (48).…”

“…While the mechanism by which niacin influences HDL remains unclear, it appears to be independent of its activation of GPR109A (47). Formation of COX-1-dependent PGD 2 and PGE 2 by cutaneous dendritic cells, followed by COX-2-dependent formation of PGE 2 by keratinocytes, results in flushing via activation of vascular DP1, EP2, and EP4 receptors (24), an adverse effect of niacin that compromises patient adherence (47).…”

Effects of Established Hypolipidemic Drugs on HDL Concentration, Subclass Distribution, and Function

“…It is not quite clear how niacin leads to an increase in HDL-C levels, and various theories have been proposed (Soudijn et al 2007). These include the ability of niacin to inhibit CETP (Hernandez et al 2007), to induce ABCA1 expression (Rubic et al 2004), and to reduce HDL catabolism (Bodor and Offermanns 2008).…”

Synergistic fungicidal efficacy of formulations of neem oil, nicotinic acid and Ferula asafoetida with .ALPHA., .BETA.-unsaturated carbonyl compounds against Sclerotium rolfsii ITCC 5226 & Macrophomina phaseolina ITCC 0482

“…The natural products, viz. neem oil (Azadirachta indica) (N1), nicotinic acid (N2) and Ferula asafoetida (N3), used in the current study have been well documented for their wide range of applications in agriculture and pharmacology, [11][12][13][14][15][16] suggesting their biocompatibility with the environment as well as with humans and other mammals. Further, synthetic constituents selected for investigation possess i) a carbonyl group in conjugation with a double bond as this is reported to have a profound effect on the activity of various pharmacologically important compounds, 17,18) and ii) a basic chalcone nucleus (1c-1i), as several naturally occurring and synthetic compounds with chalcone as the core nucleus have been reported to have broad spectrum biological activity, 19) such as insecticidal, 20) antifungal, 21) antioxidant, [22][23][24] tyrosinase inhibitory, antimitotic, 26) and antibacterial activity.…”