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Review
. 2008 Mar;153 Suppl 1(Suppl 1):S68-75.
doi: 10.1038/sj.bjp.0707528. Epub 2007 Nov 26.

Nicotinic acid: an old drug with a promising future

E T Bodor  1 , S Offermanns
Affiliations
Review

Nicotinic acid: an old drug with a promising future

E T Bodor et al. Br J Pharmacol. 2008 Mar.

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 flush-reducing co-medications of nicotinic acid and novel drugs targeting the nicotinic acid receptor will provide future therapeutic options for the treatment of dyslipidaemic disorders.

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Figures

Figure 1
Figure 1
Mechanisms of nicotinic acid-induced changes in lipid metabolism. ATGL, adipocyte-triacylglycerol-lipase; CETP, cholesterol ester transfer protein; FFA, free fatty acid; HSL, hormone-sensitive lipase; PKA, protein kinase A; TG, triglyceride.
Figure 2
Figure 2
Properties (a) and structures (b) of various ligands of GPR109A and GPR109B. EC50 values were determined by measuring binding of GTPγS to membranes or by measuring adenylyl cyclase inhibition. 1-IPBT-5-CA, 1-isopropyl-benzotriazole-5 carboxylic acid.
Figure 3
Figure 3
Model of GPR109A-binding nicotinic acid. (left panel) View on the extracellular site of the receptor, which binds nicotinic acid (yellow) in its binding pocket from transmembrane helices 2, 3 and 7. (right panel) Model of the most important interactions of nicotinic acid with amino-acid residues of the receptor. TMH, transmembrane helix; ECL, extracellular loop. The coordinates used to draw the model were generated by J Lättich and G Krause (FMP, Berlin) (Tunaru et al., 2005).
Figure 4
Figure 4
Proposed mechanism of the nicotinic acid-induced flushing response. AA, arachidonic acid; COX-1, cyclooxygenase-1; PGD2, prostaglandin D2; PGE2, prostaglandin E2; PLA2, phospholipase A2.
See this image and copyright information in PMC

References

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