Better, safer Fen-Phen in future?
Better, safer Fen-Phen in future?
BOSTON, Jul 25, 2002 (United Press International via COMTEX) -- An international team of medical scientists reported new findings Thursday that may make future weight-loss medication safer than the diet drug combination of Fen-Phen, which caused heart valve problems and was pulled from the market.
U.S. and Argentine researchers have unraveled the complex biochemical cascade of changes in the brain that create the appetite suppressant effects of d-FEN, one of the two components of the once-popular fenfluramine- phentermine off-label diet combo.
By teasing apart how d-FEN affects brain chemistry and damages the heart, researchers hope to prevent and treat obesity without any of the life-threatening side effects. They also said their findings could shed light on other eating disorders, such as anorexia nervosa and the wasting syndromes often seen in cases of chronic illness.
"The fact that it could be involved in so many things just speaks to the importance of this brain pathway when it comes to energy balance, " researcher Joel Elmquist, a neuroscientist and endocrinologist at Beth Israel Deaconess Medical Center in Boston, told United Press International.
Although Fen-Phen was among the most effective diet drugs and was prescribed to millions of people in the United States since it first came to market in 1992, the Food and Drug Administration withdrew it from clinical use in 1997 because of reports of heart valve deterioration.
Scientists knew d-FEN worked by elevating levels of the biochemical serotonin, which in the brain is involved in sleep, appetite and depression. But increasing serotonin activity elsewhere in the body often triggers a host of other, unwanted consequences.
The exact step-by-step breakdown of the d-FEN pathway leading to suppressed appetite was not known until now. In experiments in rats, the research team, led by neuroscientist Lora Heisler of Harvard Medical School in Cambridge, Mass., gave rodents the drug while monitoring precise brain cell activity using electrodes.
The investigators discovered d-FEN triggers a chain reaction inside the hypothalamus, the nugget of tissue at the base of the brain that maintains the body's status quo when it comes to factors such as blood pressure and body temperature. Specifically, the drug pushes a few cells in the hypothalamus to secrete more hormones known as melanocortins.
"The melanocortin pathway is one of the hottest areas in the pharmaceutical area right now because (it is) required for normal body weight distribution, " Elmquist said. "What's interesting about our work is how we've now tied the melanocortin with the serotonin pathway, which would help explain a link between the disorders such as depression with physiological effects."
Heisler and the team found stimulating these cells led to significantly decreased food intake. Mice with an abnormally low number of these cells were obese. Blocking melanocortin activity in the brain also blunted the effectiveness of d-FEN.
Future drugs that target these melanocortin-linked cells selectively instead of the wider-acting serotonin pathways might combat obesity more effectively than d-FEN as well as avoid pumping serotonin into the blood where it appears to affect the heart.
Geneticist Greg Barsh of Stanford University in California cautioned that "like d-FEN, melanocortins control other processes besides body weight, and any treatment based on melanocortins will need to consider potential side effects."
The scientists describe their findings in the July 26 issue of the journal Science.
(Reported by Charles Choi, UPI Science News, in New York)
Author not available, BETTER, SAFER FEN-PHEN IN FUTURE?. , United Press International, 07-25-2002.
|
