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 Arena's discovery of a niacin receptor termed GPR109a.
believes that activation of one or both of those receptors may be responsible for niacin's beneficial effects, and the undesirable side effects. Semple
said data from the joint Arena-Merck research program reinforces the hypothesis that it may be possible to identify a compound that activates the niacin receptor without causing flushing, thereby separating the beneficial effects on fatty acids from the flushing side effect.
"This work has not been reported previously and has been carried out within the last three years," Semple
...Graeme Semple, Ph.D., is Vice President of Discovery Chemistry at Arena Pharmaceuticals, San Diego, Calif.