Anorectic activity of fluoxetine and norfluoxetine in mice, rats and guinea-pigs

M. Anelli, A. Bizzi, S. Caccia, A. M. Codegoni, C. Fracasso, S. Garattini

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The present study aimed to establish the role of the metabolite norfluoxetine in the anorectic activity of fluoxetine, and to relate the anorectic doses (ED50) to the brain concentrations of the parent drug and its metabolite. Fluoxetine showed anorectic activity at increasing intraperitoneal doses (ED50 = 39.1, 34.7 and 21.7 μmol kg-1 in mouse, rat and guinea-pig, respectively) and norfluoxetine was slightly more active (24.3, 22.9 and 19.1 μmol kg-1, respectively) in all three species. In terms of maximum concentration (C(max)) and area under the curve (AUC) within the experimental period (0-90 min), brain concentrations varied widely and were poorly related to the dose, guinea-pig appeared to be much more sensitive to fluoxetine than was mouse or rat. Administered norfluoxetine was present in the brain of the three species in approximately the same order as fluoxetine, i.e. lower in guinea-pig than in mouse or rat. The C(max) and AUC of norfluoxetine after fluoxetine administration was 50-60% of the values after an equiactive dose of norfluoxetine in mouse and guinea-pig, and more than 80%, in rat.

Original languageEnglish
Pages (from-to)696-698
Number of pages3
JournalJournal of Pharmacy and Pharmacology
Issue number8
Publication statusPublished - 1992

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Pharmacology


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