title: Quantitative positron emission tomography studies of the serotonin transporter in humans previously treated with the appetite suppressants fenfluramine or dexfenfluramine.
abstract: OBJECTIVE
  The appetite suppressants fenfluramine and dexfenfluramine were widely prescribed before being withdrawn from the market in 1997.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.
  
  
  METHODS
  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.affiliation: Department of Psychiatry and Behavioral Sciences, The Johns Hopkins School of Medicine, Baltimore, MD 21224, USA. umccann@jhmi.edu
authors.forename: Una D
authors.initials: UD
authors.lastname: McCann
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szabo
authors.forename: Melin
authors.initials: M
authors.lastname: Vranesic
authors.forename: Esen
authors.initials: E
authors.lastname: Seckin
authors.forename: Gary
authors.initials: G
authors.lastname: Wand
authors.forename: Anna
authors.initials: A
authors.lastname: Duval
authors.forename: Robert F
authors.initials: RF
authors.lastname: Dannals
authors.forename: George A
authors.initials: GA
authors.lastname: Ricaurte
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001067:Appetite Depressants / Q000009:adverse effects*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D020372:Dexfenfluramine / Q000009:adverse effects*; D005260:Female; D005277:Fenfluramine / Q000009:adverse effects*; D006801:Humans; D007546:Isoquinolines; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D001067:Appetite Depressants; D002250:Carbon Radioisotopes; D007546:Isoquinolines; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D005277:Fenfluramine; C058079:McN 5652; D020372:Dexfenfluramine