title: Comparative studies on the anorectic activity of d-fenfluramine in mice, rats, and guinea pigs.
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.
authors.affiliation: Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Mennini
authors.forename: A
authors.initials: A
authors.lastname: Bizzi
authors.forename: S
authors.initials: S
authors.lastname: Caccia
authors.forename: A
authors.initials: A
authors.lastname: Codegoni
authors.forename: C
authors.initials: C
authors.lastname: Fracasso
authors.forename: E
authors.initials: E
authors.lastname: Frittoli
authors.forename: G
authors.initials: G
authors.lastname: Guiso
authors.forename: I M
authors.initials: IM
authors.lastname: Padura
authors.forename: C
authors.initials: C
authors.lastname: Taddei
authors.forename: A
authors.initials: A
authors.lastname: Uslenghi
mesh_terms: D000818:Animals; D001067:Appetite Depressants; D001921:Brain / Q000378:metabolism; D005277:Fenfluramine / Q000378:metabolism / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008928:Mitochondria / Q000378:metabolism; D009642:Norfenfluramine / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism; D013045:Species Specificity; D013574:Synaptosomes / Q000378:metabolism; D014316:Tritium
chemical_list: D001067:Appetite Depressants; D011985:Receptors, Serotonin; D014316:Tritium; D009642:Norfenfluramine; D005277:Fenfluramine