Comparative studies on the anorectic activity of d-fenfluramine in mice,rats, and guinea pigs |
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Authors: | Tiziana Mennini Adalgisa Bizzi Silvio Caccia Annamaria Codegoni Claudia Fracasso Emanuela Frittoli Giovanna Guiso Ines Martin Padura Carlo Taddei Angela Uslenghi Silvio Garattini |
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Affiliation: | (1) Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, 20157 Milan, Italy |
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Abstract: | Summary 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.Send of fprint requests to T. Mennini at the above address |
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Keywords: | d-Fenfluramine Anorectics Rats Mice Guinea pigs Serotonin Serotonin receptors Serotonin uptake Serotonin release |
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