Purpose: The appetite suppressants fenfluramine and dexfenfluramine were widely prescribed before being withdrawn from the market in 1997.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 [11C] 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 [11C] McN5652. Global and regional distribution volumes (DVs) of [11C] 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 [11C]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.
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging
- Cancer Research