mk-0524 and Weight-Loss

Nicotinic acid (niacin) is one of the oldest drugs used to treat dyslipidemia. In addition to modestly lowering low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a), niacin is currently the most effective available agent for raising high-density lipoprotein cholesterol (HDL-C). Despite its well-documented beneficial effects on lipids, the clinical use of niacin has been limited by its side effect profile, notably flushing. This sensation of cutaneous vasodilatation and burning has limited patient compliance and is a frequent cause of discontinuation of the drug. While pretreatment with nonsteroidal anti-inflammatory agents, such as aspirin, may reduce the incidence of flushing, present-day niacin still results in flushing in many patients. Recent studies have elucidated what we currently understand as the molecular mechanism that mediates niacin-induced flushing, specifically that niacin acting through its receptor stimulates the production of several prostaglandins, including prostaglandin (PG) I(2), PGE(2) and PGD(2). Laropiprant is a potent, highly selective prostaoid DP(1) receptor antagonist that decreases the incidence and intensity of niacin-induced flushing without affecting its beneficial lipid effects. Thus, laropiprant, when used in conjunction with niacin, can improve the tolerability of niacin and aid in medication compliance. This paper reviews the data suggesting the importance of raising HDL with niacin, describes the pharmacology of the drug, and examines the potential beneficial effects of combining niacin with laropiprant.

Topics: Cholesterol, HDL; Drug Tolerance; Exercise; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Lipoproteins, HDL; Niacin; Receptors, Immunologic; Receptors, Prostaglandin; Safety; Weight Loss