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Toward improved forms of a time-tested cholesterol-fighter

CHICAGO, March 27 New discoveries offer promise for developing drugs that improve on the therapeutic profile of niacin, the inexpensive, time-tested B-vitamin that boosts levels of HDL cholesterol the good cholesterol with the potential to protect people against heart attacks and stroke, scientists reported today.

Graeme Semple, Ph.D., Vice President of Discovery Chemistry at Arena Pharmaceuticals, San Diego, Calif., described new insights into developing drugs that raise HDL via the same mechanism as niacin in a report scheduled for presentation at the 233rd national meeting of the American Chemical Society, being held here this week.

In small doses, niacin is the familiar B-complex vitamin, which helps the body metabolize or breakdown carbohydrates, fats and protein into compounds that the body needs to maintain good health. In the high doses prescribed by a physician, niacin can increase HDL by as much as 35 percent and reduce levels of artery-clogging triglycerides by 50 percent.

Doctors have known since the 1970s that niacin can reduce the risk of heart attacks and strokes, but it has not been prescribed as widely as newer and more costly medications known as statins.

The use of niacin is limited by its side-effects, including a highly uncomfortable skin flushing, which contributes significantly to poor patient compliance, Semple explained. Since currently marketed cholesterol drugs have a more modest HDL-raising activity than niacin, better tolerated HDL-targeted therapies with improved efficacy could provide additional clinical benefits to patients and potentially reduce the risk of heart attack and stroke.

Semple described research toward that goal, including Arenas discovery of a niacin receptor termed GPR109a. It is among a family of so-called G protein-coupled receptors (GPCRs) that have long been considered among scientists as good targets for the development of new drugs.

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