Quantitative positron emission tomography studies of the serotonin transporter in humans previously treated with the appetite suppressants fenfluramine or dexfenfluramine

Una D. McCann, Zsolt Szabo, Melin Vranesic, Esen Seckin, Gary Wand, Anna DuVal, Robert F. Dannals, George A. Ricaurte

Research output: Contribution to journalArticlepeer-review

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Purpose: The appetite suppressants fenfluramine and dexfenfluramine were widely prescribed before being withdrawn from the market in 1997.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 [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.

Original languageEnglish (US)
Pages (from-to)151-157
Number of pages7
JournalMolecular Imaging and Biology
Volume9
Issue number3
DOIs
StatePublished - May 2007

Keywords

  • Amphetamines
  • Neurotoxicity
  • Serotonin

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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