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 Ricaurte

Research output: Contribution to journalArticle

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

Fingerprint

Fenfluramine
Serotonin Plasma Membrane Transport Proteins
Papio
Positron-Emission Tomography
Serotonin
Brain
Primates
Hydroxyindoleacetic Acid
Weight Loss
Electrons
Ligands
Pharmaceutical Preparations

Keywords

  • Fenfluramine
  • Neurotoxicity
  • Positron Emission Tomography
  • Serotonin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pharmacology

Cite this

Fenfluramine-induced loss of serotonin transporters in baboon brain visualized with PET. / Scheffel, Ursula; Szabo, Zsolt; Mathews, William B; Finley, Paige A.; Yuan, Jie; Callahan, Brian; Hatzidimitriou, George; Dannals, Robert F; Ravert, Hayden T.; Ricaurte, George.

In: Synapse, Vol. 24, No. 4, 12.1996, p. 395-398.

Research output: Contribution to journalArticle

Scheffel, Ursula ; Szabo, Zsolt ; Mathews, William B ; Finley, Paige A. ; Yuan, Jie ; Callahan, Brian ; Hatzidimitriou, George ; Dannals, Robert F ; Ravert, Hayden T. ; Ricaurte, George. / Fenfluramine-induced loss of serotonin transporters in baboon brain visualized with PET. In: Synapse. 1996 ; Vol. 24, No. 4. pp. 395-398.
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