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Quantitative Positron Emission Tomography Studies of the Serotonin Transporter in Humans Previously Treated with the Appetite Suppressants Fenfluramine or Dexfenfluramine

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Publisher Springer
Date 2007 May 3
PMID 17473958
Citations 1
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Abstract

Purpose: The appetite suppressants fenfluramine and dexfenfluramine were widely prescribed before being withdrawn from the market in 1997. Both drugs are known to have the potential to damage brain serotonin (5-HT) axons and axon terminals in animals, including nonhuman primates. This study used quantitative positron emission tomography (PET) with [(11)C] McN5652, a serotonin transporter (SERT) ligand to determine whether humans previously exposed to fenfluramines showed reductions in SERT binding parameters.

Procedures: Subjects previously treated with fenfluramines for weight loss (N = 15) and age-matched controls (N = 17) underwent PET studies with [(11)C] McN5652. Global and regional distribution volumes (DVs) of [(11)C] McN5652 were compared in the two subject groups using parametric statistical analyses.

Results: Compared to controls, subjects previously exposed to fenfluramines had significant reductions in [(11)C]McN5652 binding in 14 of 15 regions of interest, more than four years after drug discontinuation.

Conclusions: These results are the first to provide direct evidence for fenfluramine-induced 5-HT neurotoxicity in humans.

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