Fenfluramine-induced loss of serotonin transporters in baboon brain visualized with PET

Ursula Scheffel, Zsolt Szabo, William B. Mathews, Paige A. Finley, Jie Yuan, Brian Callahan, George Hatzidimitriou, Robert F. Dannals, Hayden T. Ravert, George A. Ricaurte

Research output: Contribution to journalArticlepeer-review

Abstract

The present study sought to determine whether or not Positron Emission Tomography (PET) with the newly developed positron emitting serotonin (5-HT) transporter ligand, (+)[11C]McN-5652, could be used to detect fenfluramine- induced 5-HT neurotoxicity in the brain of living primates (baboons). Six PET imaging studies were performed: three before treatment with fenfluramine (5 mg/kg, s.c., twice daily for 4 days) and three after (18, 45, and 81 days after treatment). The dose of fenfluramine used in this study (5 mg/kg) is known to produce 5-HT neurotoxicity in primates, and to be approximately two times higher than a dose of fenfluramine reported to produce small and inconsistent weight loss in baboons (2 mg/kg). Following fenfluramine treatment, marked lasting reductions in regional brain specific binding of (+)[11C]McN-5652 were found by means of PET. Findings with PET corresponded well with post-mortem neurochemical findings indicative of serotonergic neurotoxicity (lasting depletions of regional brain 5-HT, 5-HIAA, and 5-HT uptake sites). These results suggest that PET imaging with (+)[11C]McN- 5652 will be useful for evaluating the 5-HT neurotoxic potential of fenfluramine and related drugs in living humans.

Original languageEnglish (US)
Pages (from-to)395-398
Number of pages4
JournalSynapse
Volume24
Issue number4
DOIs
StatePublished - Dec 1996

Keywords

  • Fenfluramine
  • Neurotoxicity
  • Positron Emission Tomography
  • Serotonin

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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