Abstract
The anorexic and behavioural effects of Norfenfluramine were studied in rats. Two separate experiments were conducted involving administration by intra-peritoneal and sub-cutaneous routes respectively. Behavioural effects were assessed by time sampling categorisation on Days 1 and 14 of a 20 day chronic study and anorexic effects by daily weighing. Norfenfluramine was found to be a potent anorexiant, to which tolerance is established fairly quickly. It was also found to possess sedative properties after acute administration, but marked stimulant properties after 14 days chronic administration. These results are similar to those previously reported in a study of Fenfluramine, although the behavioural effects of Norfenfluramine are more marked. The results implicate Norfenfluramine in the anorexic and behavioural effects of Fenfluramine, and provide indirect confirmation of the suggestion made in an earlier paper that Fenfluramine may have chronic stimulant properties.
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Beckett, A. H., Brookes, L. G.: The absorption and urinary excretion in man of Fenfluramine and its main metabolite. J. Pharm. Pharmacol. 19, Suppl., 425–495 (1967)
Belvedere, G., Tognoni, G., Morselli, P. L.: A new sensitive gas Chromatographic method for the determination of Fenfluramine in biological specimens. Europ. J. clin. Pharmacol. 5, 62–64 (1972)
Blundell, J. E., Latham, C. J., Lesham, M. B.: Biphasic action of a 5-hydroxytryptamine inhibitor on Fenfluramine induced Anorexia. J. Pharm. Pharmacol. 25, 492–494 (1973)
Bruce, R. B., Maynard, W. R.: Fenfluramine metabolism. J. pharm. Sci. 57, 1173–1175 (1968)
Campbell, D. B.: Absorption, Distribution and Metabolism of Fenfluramine. La Vie Medicale au Canada Francais 2, 34–40 (1973)
Clineschmidt, B. V.: 5,6-Dihydroxytryptamine: Suppression of the anorexigenic action of Fenfluramine. Europ. J. Pharmacol. 24, 405–409 (1973)
Costa, E., Groppetti, A., Revuelta, A.: Action of Fenfluramine on monoamines stores of rat tissue. Brit. J. Pharmacol. 41, 57–64 (1971)
Costa, E., Revuelta, A.: Norfenfluramine and serotonin turnover rate in the rat brain. Biochem. Pharmacol. 21, 2385–2393 (1972)
Duhault, J., Verdavainne, C.: Modification du taux de serotonine cerebral chez le rat par les trifluromethylphenyl-2-ethyl-amino propane (Fenfluramine 768S). Arch. int. Pharmacodyn. 170, 276–286 (1967)
Everitt, B. J., Hackett, N. B.: Central stimulant action of Fenfluramine in the rat. Brit. J. Pharmacol. 44, 342–343 (1972)
Funderbunk, W. H., Hazelwood, J. C., Ruckart, R. T., Ward, J. W.: Is 5-hydroxytryptamine involved in the mechanism of action of Fenfluramine? J. Pharm. Pharmacol. 23, 468–469 (1971)
Garattini, S.: Differences and similarities between Fenfluramine and amphetamine. La Vie Medicale au Canada Francais 2, 21–27 (1973)
Ghezzi, D., Samanin, R., Bernasconi, S., Tognoni, G., Gerna, M., Garattini, S.: Effects of thymoleptics on Fenfluramine-Induced depletion of brain serotonin in rats. Europ. J. Pharmacol. 24, 205–210 (1973)
Goudie, A. J., Taylor, M.: Time sampling of rat exploratory behaviour: a reliable screening test for the C.N.S. effects of anorexic agents. Psychopharmacologia (Berl.) 35, 1–12 (1974)
Jespersen, S., Scheel-Krüger, J.: Antagonism by methysergide of the 5-hydroxytryptamine like action of toxic doses of Fenfluramine in dogs. J. Pharm. Pharmacol. 22, 637–638 (1970)
Jespersen, S., Scheel-Krüger, J.: Evidence for a difference in mechanism of action between fenfluramine and amphetamine induced anorexia. J. Pharm. Pharmacol. 25, 49–54 (1973)
Le Douarec, J. C.: The role of norfenfluramine in fenfluramine activity. Paper presented at international seminar of fenfluramine and obesity, Nassau, Bahamas. Reported in supplement to S.Afr. med. J. (1971)
Le Douarec, J. C., Schmitt, H., Laubie, M.: étude Pharmacologique de la Fenfluramine et des ses isomers optiques. Arch. int. Pharmacodyn. 161, 206–232 (1966)
Magour, S., Coper, H., FÄhndrich, Ch.: The effects of chronic treatment with d-Amphetamine on food intake, body weight, locomotor activity and subcellular distribution of the drug in the rat brain. Psychopharmacologia (Berl.) 34, 45–54 (1974)
McKearney, J. W.: Schedule dependant effects. In: Schedule effects: Drugs, drinking aggression. R. M. Gilbert and J. D. Keehn, Eds. Toronto: University of Toronto Press 1972
Morgan, C. D., Cattabeni, F., Costa, E.: Methamphetamine, fenfluramine and their N-dealkylated metabolites; Effects on monoamine concentrations in rat tissues. J. Pharmacol. exp. Ther. 180, 127–135 (1972)
Norton, S.: Amphetamine as a model for hyperactivity in the rat. Physiol. Behav. 11, 181–186 (1973)
Opitz, K., Weischer, M. L.: The urinary excretion of anorexigenic phenylalkylamines. Arzneimittel-Forsch. 16, 1311–1313 (1966)
Oswald, I., Lewis, S. S., Dunleavy, D. L. F., Brezinova, V., Briggs, M.: Drugs of dependence though not of abuse: Fenfluramine and Imipramine. Brit. med. J. 1971II, 370–373
Samanin, R., Ghezzi, D., Valzelli, L., Garrattini, S.: The effects of selective lesioning of brain serotonin or catecholamine containing neurones on the anorectic activity of fenfluramine and amphetamine. Europ. J. Pharmacol. 19, 318–322 (1972)
Southgate, P. J., Mayer, S. R., Boxall, E., Wilson, A. B.: Some 5-hydroxytryptamine like actions of Fenfluramine: a comaprison with (+) amphetamine and diethylpropion. J. Pharm. Pharmacol. 23, 600–605 (1971)
Taylor, M., Goudie, A. J.: Chronic anorexic and behavioural effects of the fenfluramine derivative “SE 780” in rats. Psychopharmaoologia (Berl.) 35, 13–17 (1974)
Taylor, M., Goudie, A. J., Williams, A.: The effects of chronic Fenfluramine on behaviour and body weight. Psychopharmacologia (Berl.) 31, 63–76 (1973)
Taylor, M., Goudie, A. J., She Key Mortimore, Wheeler, T. I.: Comparison between behaviours elicited by high doses of amphetamine and fenfluramine Implications for the concept of stereotypy. Psychopharmacologia (Berl.) (in prep.)
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The work reported here forms part of an M.Sc. thesis to be submitted to the Department of Psychology, U.C.N.W. Bangor.
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Goudie, A.J., Taylor, M. & Wheeler, T.J. Chronic anorexic and behavioural effects of the fenfluramine metabolite, norfenfluramine: An evaluation of its role in the actions of fenfluramine. Psychopharmacologia 38, 67–74 (1974). https://doi.org/10.1007/BF00421288
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DOI: https://doi.org/10.1007/BF00421288