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An abandoned weight-loss drug gets a makeover ‎

8/17 18:09:23

Remember the experimental weight-loss drug rimonabant, touted as a potential "miracle pill" that could help obese smokers kick the habit,爈ose weight燼nd keep it off for two years?

燤arketed in Europe as Acomplia, the drug made it well into the燯.S. Food and Drug Administration's燼pproval process before it was linked in 2008 to a doubling of depression risk in those taking it.

The drug ended up withdrawn from the European market and pulled from FDA consideration, another failed medication on the ash heap of爋besity爐reatments.

Or maybe not. A new study finds that a structural modification that prevents the active molecule from entering the brain might give a new lease on life to the the whole idea of promoting weight loss by manipulating the body's cannibinoid-receptor system.

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In a study published in the journal Cell Metabolism, scientists gave obese rats a chemical variant of the drug that gave rimonabant its ability to bring about weight loss. The resulting agent, called JD5037, "robustly reduces food intake, body weight and adiposity" and was "devoid of behavioral effects," the researchers reported.

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It did so by blocking the body's receptors for endocannibinoids -- messenger chemicals that play a role in metabolism and energy use as well as in mood, pain perception and satiety. While many of the body's cannibinoid receptors reside in the brain (hence their role in mood), some also operate in such organs as the liver and in fat -- which, in the obese, plays a powerful role in sending signals that say, in effect, "feed me."

But since scientists suspect that blocking cannabinoid receptors in the brain may wreak havoc on mood, the key here was to find a way to block cannabinoid receptors throughout the body but not in the brain's cortical regions.

This is what they did, modifying a cannabinoid blocker called SLV319 so that it could not penetrate the blood-brain barrier.

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