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The Food and Drug Administration recently approved the drugdexfenfluramine as an appetite suppressant in the treatment of
obesity. This drug became controversial after a study using rats revealed that high doses of dexfenfluramine may cause brain
damage. While the study was criticized for using unrealistic doses, the principal researcher suggested that the danger may
lie in long-term use. The drug, however, is available in 65 countries, and few negative side effects have surfaced in more
than a decade of use.
Dexfenfluramine apparently works by increasing the release of a brain neurotransmitter called serotonin while inhibiting its re-uptake. This extends the effects of serotonin, which include a reduced craving for sweets and a heightened feeling of fullness, even after a low-calorie meal.
Dexfenfluramine also increases diet-induced thermogenesis after a high-carbohydrate meal. Thermogenesis refers to the conversion of calories into heat, which reduces the possibility of calories being stored as bodyfat. The drug also increases insulin sensitivity. This is a major problem for the obese, who usually over secrete insulin, which is the major fat-storage hormone.
A recent study published in the International Journal of Obesity (19:749-51, 1995) found that dexfenfluramine lowers blood pressure, serum-insulin levels and serum cholesterol. This effect on blood lipids, or fats, however, prompted another study, which was reported in the same journal. In this study, the researchers sought to define the precise mechanism by which dexfenfluramine decreases blood fats. What the researchers found should eliminate any thoughts bodybuilders have of taking dexfenfluramine for weight loss.
The drug works by inhibiting catecholamine release. Catecholamines, such as epinephrine, are integral to the process of fat release during exercise. When you train, you secrete greater-than-normal amounts of epinephrine from your adrenal medulla. The epinephrine then travels to fat cells, where it stimulates an enzyme appropriately called hormone-sensitive lipase. This enzyme in turn causes an increase of an intracellular substance called cyclic AMP, resulting in fat release.
The new study found that in test-tube experiments, dexfenfluramine inhibited this entire fat-release process. While this will lower blood-triglyceride (fat) levels, it's not exactly advantageous to someone trying to burn fat through exercise. Whether the doses prescribed for weight loss in humans will produce this effect in the body remains to be seen.