Comparative studies on the anorectic activity of d-fenfluramine in mice, rats, and guinea pigs.
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.
Mennini
T
T
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Bizzi
A
A
Caccia
S
S
Codegoni
A
A
Fracasso
C
C
Frittoli
E
E
Guiso
G
G
Padura
I M
IM
Taddei
C
C
Uslenghi
A
A
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
D001067:Appetite Depressants; D011985:Receptors, Serotonin; D014316:Tritium; D009642:Norfenfluramine; D005277:Fenfluramine