Comparative studies on the anorectic activity of d-fenfluramine in mice, rats, and guinea pigs

Tiziana Mennini, Adalgisa Bizzi, Silvio Caccia, Annamaria Codegoni, Claudia Fracasso, Emanuela Frittoli, Giovanna Guiso, Ines Martin Padura, Carlo Taddei, Angela Uslenghi, Silvio Garattini

Research output: Contribution to journalArticlepeer-review

Abstract

The present study compares the anorectic activity of d-fenfluramine and its metabolite d-norfenfluramine in three animal species. d-Fenfluramine and d-norfenfluramine show anorectic activity at increasing doses (ED50) in rats, guinea pigs, and mice, d-norfenfluramine being more active than d-fenfluramine in all three species. Equiactive anorectic activities are reached with different brain levels of d-fenfluramine and d-norfenfluramine, guinea pigs being the most sensitive species, followed by rats then mice. The metabolite most probably plays a major role in the anorectic effect of d-fenfluramine in guinea pigs, contributes to the anorectic activity in rats, but adds little to the action of the parent drug in mice. The different sensitivity to d-fenfluramine and d-norfenfluramine in these three species does not appear to be explained by a number of biochemical parameters, including serotonin uptake or release, receptor subtypes, or 3H-d-fenfluramine binding and uptake.

Original languageEnglish
Pages (from-to)483-490
Number of pages8
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume343
Issue number5
DOIs
Publication statusPublished - May 1991

Keywords

  • Anorectics
  • d-Fenfluramine
  • Guinea pigs
  • Mice
  • Rats
  • Serotonin
  • Serotonin receptors
  • Serotonin release
  • Serotonin uptake

ASJC Scopus subject areas

  • Pharmacology

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