THURSDAY, July 20 (HealthDay News) -- Research with mice has identified how diet drugs such as Fen-Phen work to activate the brain chemical serotonin, which curbs appetite.

The finding could lead to new diet drugs that don't have the dangerous cardiac side effects associated with Fen-Phen, which led it to be banned in 1997, after it had been used for almost a decade, the researchers said.

"We wanted to look at the pathways and molecules involved in the anorexic properties of drugs like Fen-Phen," said lead researcher Dr. Joel Elmquist, a professor of internal medicine at the University of Texas Southwestern Medical Center at Dallas, and director of the Center for Hypothalamic Research.

Elmquist noted that what was significant about Fen-Phen was that it did suppress appetite and result in weight loss. "But the mechanism and pathways in the brain that were responsible for those actions were largely unknown," he said.

In their study, Elmquist and his colleagues tested the effect of several drugs that alter serotonin levels in the brains of mice. They found that serotonin activates some neurons and melanocortin-4 receptors, or MC4Rs, to curb appetite, and at the same time blocks other neurons that normally act to increase appetite.

The report is published in the July 20 issue of Neuron.

"This is more data that suggests that the melanocortin pathway is a key pathway in your brain that affects food intake, body weight and glucose," Elmquist said. "Our data suggest that serotonin is involved in affecting this pathway."

This dual effect helps explain how such drugs cause weight loss. The findings also reinforce the role of serotonin, which regulates emotions, mood and sleep, in affecting the brain's melanocortin system, a key pathway that controls body weight, he said.

Learning how these drugs work, one could potentially target these pathways and avoid the harmful side effects associated with a drug like Fen-Phen while still controlling the feeling of hunger, Elmquist said.

"The goal of pharmaceutical companies is to identify the neurons that are key for body-weight control and within those neurons the key signaling pathways," Elmquist said. "If you could target those, you could have a more effective and safe treatment," he said.

One expert agrees that it may be possible to develop new safe and effective diet drugs, but for use only as a bridge to lifestyle changes.

"This finding really shows us where we can focus our efforts for new therapeutics that target the receptor they have identified as the one that's key in the regulation of food intake," said Philip Smith, director of the Division of Diabetes, Endocrinology and Metabolic Diseases at the National Institute of Diabetes, Digestive and Kidney Diseases.

Smith thinks that these new drugs could target centers of the brain that effect behavior. "The key is what motivates behaviors like overeating and smoking," he said. "Drugs that target the pathways found in this study are likely to target motivational pathways that are involved with serotonin."

But drugs alone aren't the answer to the growing obesity epidemic, Smith said. "The only hope is that we actually modify lifestyle," he said.

"The question is, can we find drugs that will help enable that? Not something that would be a lifetime drug. But just like a nicotine patch, one could imagine a patch that would get you through the hardest part of losing weight so that you could actually change your lifestyle, and you are not constantly fighting the urge to eat," Smith said. "It is lifestyle change that will really make a dent in the obesity epidemic."

More information

The National Institute of Diabetes and Digestive and Kidney Diseases can tell you more about dieting.

SOURCES: Joel Elmquist, D.V.M., Ph.D., professor, internal medicine, University of Texas Southwestern Medical Center at Dallas; Philip Smith, Ph.D., director, Division of Diabetes, Endocrinology and Metabolic Diseases, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, Md.; July 20, 2006, Neuron

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