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Interaction of phentermine plus fenfluramine: neurochemical and neurotoxic effects.

Previous studies have reported the use of combined serotonergic and dopaminergic agonists in the treatment of obesity and alcoholism. Along these lines, phentermine plus fenfluramine has been suggested as a possible clinical treatment for alcohol craving. To determine the neurochemical effects of a combined treatment of phentermine plus fenfluramine, animals were injected subcutaneously with saline, phentermine 12 mg/kg, fenfluramine 16 mg/kg, or a combination of phentermine plus fenfluramine. One hour after injection, animals were sacrificed and neurochemical analysis performed. Furthermore, separate groups of animals were given the same injections 8 times, 12 hours apart, to determine the effects on body weight and to detect a possible exacerbation of fenfluramine induced toxicity. The drug combination produced a significant rise in dopamine in the striatum, greater than that seen with either drug alone. Furthermore, the addition of phentermine reduced the fenfluramine induced rise in striatal 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindolacetic acid (5-HIAA). Phentermine plus fenfluramine combination produced a greater weight loss than either drug alone, however, it did not produce a significantly greater drop in striatal serotonin or 5-HIAA levels above that induced by fenfluramine alone. Thus, while previous studies report the potentiated neurotoxicity of phentermine plus fenfluramine over fenfluramine alone, the present study does not indicate that such an effect occurs following an administration regimen analogous to that of patients treated with the drug combination.