In animals, fenfluramine alone or in combination with phentermine, produces toxic effects on brain serotonin (5-HT) neurons. In particular, the available data indicate that fenfluramine produces a distal axotomy of brain 5-HT neurons in a number of different animal species, including nonhuman primates. Whether fenfluramine also damages 5-HT neurons in humans has not been determined. The purpose of the present project is to determine whether fenfluramine alone or in combination with phentermine, damages brain 5-HT neurons in humans. To this end, we will determine whether subjects with a history of treatment with fenfluramine alone or in combiunation with phentermine, show long-term effects on 5-HT transporter density, CSF 5-HIAA concentration, 5-HT mediated neuroendocrine function, or changes in functional domains in which 5-HT has been implicated (e.g., personality, mood, cognition). These studies are intended to test the hypothesis that fenfluramine/phentermine treatment produces toxic effects on 5-HT neurons in the human brain.
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