Can obesity be fought with drugs? - Pfizer Inc. has developed hormone-like compounds that increase the metabolic rate like exercise to burn more calories without increasing appetite - Brief Article

"There are two ways to approach the treatment of obesity, a condition that affects approximately one in three Americans," according to Robert Dow, principal research investigator with Pfizer Inc., Groton, Conn. "Either you inhibit food intake. or you improve energy expenditure to get the `exercise effect.'" Pfizer has developed compounds that, in animal trials, boosted metabolic rates to mimic the exercise effect of increased calorie burning -- without exercise. The tests showed a 10-30% jump in metabolic rate. "If you have a 10% increase in energy expenditure, you're potentially looking at about a half a pound a week drop in weight," Dow points out. There are currently no drugs on the market that work this way.

The compounds do not seem to bring about one other effect of an exercise-induced hike in metabolism. "If I go out and ski all day and I come in, I'm ravenous and I eat more," Dow says. "But that sort of compensation has not been seen in the animal tests with these compounds."

The compounds are hormone mimics that act on the beta-adrenergic system, which has three sub-types of receptors in cells in the body. These receptors are stimulated by the adrenaline released in the body's fight-or-flight response to danger. One of the receptor types is predominant in the heart, where it helps raise the heart rate. A second type is involved in dilation of blood vessels and a drop in blood pressure. The third type is found in fat tissue, and it is this one that the compounds stimulate, boosting metabolism. That means they leave the other two types of receptors alone, minimizing side effects.

Animal tests of some previous similar compounds passed with flying colors, but failed in human clinical trials. Dow explains this is because they were developed before the human beta-3 adrenergic receptor had been identified. The Pfizer compounds, on the other hand, work more efficiently at that receptor, so he expects them to perform better in the human trials than their predecessors. If human clinical trials are successful, the compounds could be available within 10-15 years, Dow predicts.

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