ASSESSMENT OF FENFLURAMINE &PHENTERMINE IN HUMANS

$0M01FY2000RRNIH

Johns Hopkins University, Baltimore MD

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Abstract

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 brain 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 show long-term effects of brain 5-HT transporter density, CSF 5-HIAA concentation, 5-HT mediated neuroendocrine function, or changes in function domains in which 5-HT has been implicated, e.g., personality, mood and cognition. The extent of possible damage to brain serotonin neurons will be determined through a neuropschiatric evaluation, PET scans with [11C}McN-5652, lumbar puncture to collect cerebrospinal fluid, and brain hormone test with m-CPP to examine neuroendocrine function. "

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