PURPOSE: The appetite suppressants fenfluramine and dexfenfluramine were widely prescribed before being withdrawn from the market in 1997.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.
PURPOSE: The appetite suppressants fenfluramine and dexfenfluramine were widely prescribed before being withdrawn from the market in 1997.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.
Authors: H M Connolly; J L Crary; M D McGoon; D D Hensrud; B S Edwards; W D Edwards; H V Schaff Journal: N Engl J Med Date: 1997-08-28 Impact factor: 91.245
Authors: U Scheffel; Z Szabo; W B Mathews; P A Finley; R F Dannals; H T Ravert; K Szabo; J Yuan; G A Ricaurte Journal: Synapse Date: 1998-06 Impact factor: 2.562