Researchers Find How Banned Diet Drug Fenfluramine Worked

Researchers at Beth Israel Deaconess Medical Center have found the pathway in the brain that explains how the diet drug fenfluramine worked to help people lose weight.

Researchers are hopeful that their findings will lead to a new anti-obesity treatment without fenfluramine's cardiac side effects.

The study, published in the journal Science, also suggests that this same pathway regulates body weight at both ends of the weight spectrum from obesity to anorexia.

Researchers believe that fenfluramine increases the availability of serotonin in the brain, which then affects the activity of the melanocortins. Melanocortins are linked with regulation of weight by working with leptin, a hormone related to obesity. Reduced activity of melanocortins can lead to obesity so researchers believe that fenfluramine may have worked by causing an increase in the activity of the melanocortins, which reduced the appetite of those taking the drug.

Researchers gave rodents fenfluramine while monitoring their brain activity using electrodes. They found that fenfluramine triggered a chain reaction inside the hypothalamus, that area of the brain that maintains blood pressure and body temperature. Fenfluramine activated cells in the hypothalamus to secrete more melanocortins.

The stimulation of these melanocortin cells led to significantly decreased appetite in the rodents. Rodents with an abnormally low number of the cells were obese and blocking the activity of melanocortin decreased the effectiveness of fenfluramine, according to the study.

"Our study has linked the serotonin system, a classic brain pathway thought to be involved with eating disorders like anorexia nervosa, to the melanocortin system, a brain pathway involved in obesity," said Joel Elmquist, senior author of the study.

Researchers are hopeful that their findings will lead to drugs that target the melanocortin cells selectively and therefore more effectively than fenfluramine, which pumped serotonin into the blood where it can have a negative effect on the heart.

Fenfluramine was banned by the U.S. Food and Drug Administration in 1997 after patients taking the drug developed cardiac problems.

Other sources: Beth Israel Deaconess, National Institute of Mental Health