Researchers identify brain pathway to explain how Fenfluramine causes weight loss

BOSTON Scientists have identified the molecular pathway in the brain that helps explain how the once-popular diet drug d-Fenfluramine (d-FEN) works to promote weight loss, a discovery reported in the July 26 issue of Science that could provide an opportunity to develop a new anti-obesity treatment without d-FEN's cardiac side effects.

The study, led by a team of researchers at Beth Israel Deaconess Medical Center (BIDMC), also suggests this same brain pathway the melanocortin system is responsible for regulation of body weight at either end of the weight spectrum from obesity at one extreme to anorexia nervosa at the other.

D-FEN, used in combination with phenteramine and known as fen-phen, was banned by the U.S. Food and Drug Administration (FDA) in 1997 after a subset of patients taking the drug developed cardiac complications.

"This study helps close the circle on the role of the melanocortin pathway and adds the serotonin system to the growing list of metabolic signals including leptin that act on the brain's melanocortin neurons, regulating food intake and body weight," explains the study's senior author Joel Elmquist, D.V.M., Ph.D., a neuroscientist and endocrinologist at BIDMC and associate professor of endocrinology and medicine at Harvard Medical School.

The diet drug d-FEN, which is the "fen" part of the fen-phen combination, first came on the market in 1992, and within five years, had been prescribed to millions of individuals who were trying to lose weight. The drug works by increasing the brain's release of serotonin, a "chemical messenger" that, among other things, helps to suppress appetite. Serotonin acts as a neurotransmitter to convey nerve impulses in the brain, and anti-obesity drugs such as fenfluramine, as well as the popular antidepressant medications fluoxetine (Prozac) and sertraline (Zoloft) work by enhancing this effect.

However, as Elmquist explains, d-FEN's popularity was relatively brief:

Contact: Bonnie Prescott
Beth Israel Deaconess Medical Center

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