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Effect of dexfenfluramine on gastric emptying of a mixed solid-liquid meal in obese subjects

Published online by Cambridge University Press:  09 March 2007

Michael Horowitz ,
Anne Maddox ,
Judith Wishart ,
Jane Vernon-Roberts ,
Barry Chatterton  and
David Shearman
Michael Horowitz
Affiliation:
Departments of Medicine and Nuclear Medicine,Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia
Anne Maddox
Affiliation:
Departments of Medicine and Nuclear Medicine,Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia
Judith Wishart
Affiliation:
Departments of Medicine and Nuclear Medicine,Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia
Jane Vernon-Roberts
Affiliation:
Departments of Medicine and Nuclear Medicine,Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia
Barry Chatterton
Affiliation:
Departments of Medicine and Nuclear Medicine,Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia
David Shearman
Affiliation:
Departments of Medicine and Nuclear Medicine,Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia
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Abstract

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Recent studies suggest that dexfenfluramine (D-fenfluramine), because of its pure serotonergic effect, may be a more potent anti-obesity agent, associated with fewer side-effects than the racemate DL-fenfluramine. The effect of dexfenfluramine on gastric emptying of a mixed solid and liquid meal was assessed with a double-isotope scintigraphic technique in eleven obese patients. Each subject took a placebo capsule on the morning and evening of the day before, and on the morning of the first gastric emptying measurement. Dexfenfluramine was then taken at a dose of 15 mg twice daily and gastric emptying measurements were performed at 5 and at 29 d after the initiation of active treatment. Dexfenfluramine significantly slowed gastric emptying of the solid meal at both 5 and 29d when compared with the placebo (P < 0.05) and also delayed emptying of solid food from the proximal stomach (P < 0.01), but no significant effect on liquid emptying was observed. No significant side-effects were reported and there was a marginal weight loss (P< 0.005) during treatment. We conclude that inhibition of gastric emptying may contribute to the efficacy of dexfenfluramine in the treatment of obesity.

Type
Gastrointestional Motility and Function
Information
British Journal of Nutrition , Volume 63 , Issue 3 , May 1990 , pp. 447 - 455
Copyright
Copyright © The Nutrition Society 1990

References

REFERENCES

Akkermans, L. M. A., Vos, A., Hoekstra, A., Roelofs, J. M. M. & Horowitz, M. (1988). The effect of ICS 205–930 (a specific 5-HT3 receptor antagonist) on gastric emptying of a solid meal in normal subjects. Gut 29, 1249–1252.CrossRefGoogle ScholarPubMed
Barone, D., Luzzani, F., Assandri, A., Galliani, G., Mennini, T. & Garattini, S. (1985). In vivo stereospecific [3H]spiperone binding in rat brain: characteristics. regional distribution. kinetics and pharmacological properties. European Journal of Pharmacology 116, 63–74.CrossRefGoogle ScholarPubMed
Berkowitz, D. M. & McCallum, R. W. (1980). Interaction of levodopa and metoclopramide on gastric emptying. Clinical Pharmacology and Therapeutics 27, 414–420.CrossRefGoogle ScholarPubMed
Blundell, J. E. & Leshem, M. B. (1974). Central action of anorexic agents: effects of amphetamine and fenfluramine in rats with lateral hypothalamic lesions. European Journal of Pharmacology 28, 81–89.CrossRefGoogle ScholarPubMed
Booth, D. A., Gibson, E. L. & Baker, B. J. (1986). Gastromotor mechanism of fenfluramine anorexia. Appetite 7, Suppl., 57–69.CrossRefGoogle ScholarPubMed
Buchheil, K. H., Engel, G., Mutschler, E. & Richardson, B. (1985). Study of the contractile effect of 5-hydroxytryptamine (5-HT) in the isolated longitudinal muscle strip from guinca-pig ileum. Nounyn-Schmiedebergs Archives of Pharmacology 329, 36–41.CrossRefGoogle Scholar
Caccia, S., Ballabio, M., Guiso, G., Rochetti, M. & Garattini, S. (1982). Special differences in the kinetics and metabolism of fenflurarmine isomers. Archives Internationales de Pharmacodynamic et de Thérapie 258, 15–28.Google Scholar
Collins, P. J., Horowitz, M. & Chatterton, B. E. (1988). Proximal, distal and total stomach emptying of a digestible solid meal in normal subjects. British Journal of Radiology 61, 12–18.CrossRefGoogle ScholarPubMed
Collins, P. J., Horowitz, M., Cook, D. J., Harding, P. E. & Shearman, D. J. C. (1983). Gastric emptying in normal subjects a reproducible technique using a single scintillation camera and computer system. Gut 24, 1117–1125.CrossRefGoogle ScholarPubMed
Consolo, S., Ladinsky, H., Forloni, G. L., Tirelli, A. S. & Garattini, S. (1980). Comparison of the effects of the stereoisomers of fenfluramine on the acetylcholine content of rat striatum, hippocampus and nucleus accumbens. Journal of Pharmacy and Pharmacology 32, 201–203.CrossRefGoogle ScholarPubMed
Costa, E., Groppetti, A. & Revuetta, A. (1971). Action of fenfluramine on monoamine stores of rat tissue. British Journal of Pharmacology 41, 57–64.CrossRefGoogle Scholar
Costall, B., Kelly, M. E., Naylor, R. J., Tan, C. C. W. & Tattersall, F. D. (1986). 5-Hydroxytryptamine M-receptor antagonism in the hypothalamus facilitates gastric emptying in the guinea-pig. Neuropharmacology 25, 1293–1296CrossRefGoogle ScholarPubMed
Davies, R. F., Rossi, J., Panksepp, J., Bean, N. J. & Zolovick, A. J. (1983). Fenfluramine anorexia: a peripheral locus of action. Physiology and Behaviour 30, 723–730.CrossRefGoogle ScholarPubMed
Even, P. & Nicolaidis, S. (1986). Dextrofenfluramine increases energy cost of muscular effect. Pharmacology, Biochemistry and Behaviour 24, 647–656.CrossRefGoogle Scholar
Finer, N., Craddock, D., Lavielle, R. & Keen, H. (1985). Dextrofenfluramine in refractory obesity. Current Therapeutic Research 38, 847–854.Google Scholar
Finer, N., Craddock, D., Lavielle, R. & Keen, H. (1987). Prolonged weight loss with dexfenflurdmine treatment in obese patients. Diabète et Métabolisme 13, 598–602.Google ScholarPubMed
Fozard, J. R. (1984). MDL 7222: a potent and highly selective antagonist at neuronal 5-hydroxytryptamine receptors. Naunyn-Schmiedebergs Archives of Pharmacology 326, 36–44.CrossRefGoogle Scholar
Garattini, S., Caccia, S., Mennini, T., Samanin, R., Consolo, S. & Ladinsky, H. (1979). Biochemical pharmacology of the anorectic drug fenfluramine: a review. Current Medical Research Opinion 6, 15–27.CrossRefGoogle Scholar
Garattini, S., Mennini, T. & Samanin, R. (1987). From fenfluramine racemate to D-fenfluramine. Specificity and potency of the effects on the serotoninergic system and food intake. In Human Obesity, vol. 499, pp., 156–166 [Wurtman, R. J. and Wurtman, J. J., editors]. New York: New York Academy of Sciences.Google Scholar
Gibbs, J. & Smith, G. P. (1978). The gut and preabsorptive satiety. Acta Hepatologica-Gastroenterologica 35, 413–416.Google Scholar
Guy-Grand, B., Apselbaum, M., Crepaldi, G., Cries, A., Lefeyre, P. & Turner, P. (1989). International trial of long-term dexfenfluramine in obesity. Lancet ii, 1142–1144.CrossRefGoogle Scholar
Hirsch, J. A., Goldberg, S. & Wurtman, R. J. (1982). Effect of (+) or (-)-enantiomers of fenfluramine or norfenfluramine on nutrient selection by rats. Journal of Pharmacy and Pharmacology 34, 18–21.CrossRefGoogle ScholarPubMed
Horowitz, M., Collins, P. J., Tuckwell, V., Vernon-Roberts, J. & Shearman, D. J. C. (1985). Fenfluramine delays gastric emptying of solid food. British Journal of Clinical Pharmacology 19, 849–851.CrossRefGoogle ScholarPubMed
Horowitz, M., Maddox, A., Harding, P. E., Maddern, G. J., Chatterton, B. E., Wishart, J. & Shearman, D. J. C. (1987). Effect of cisapride on gastric and esophageal emptying in insulin-dependent diabetes mellitus. Gastroenterology 92, 1899–1907.CrossRefGoogle ScholarPubMed
Houghton, L. A., Read, N. W., Heddle, R., Horowitz, M., Collins, P. J., Chatterton, B. & Dent, J. (1988). The relationship of the motor activity of the antrum, pylorus and duodenum to gastric emptying of a solid-liquid mixed meal. Gastroenterology 94, 1285–1291.CrossRefGoogle ScholarPubMed
Innes, J. A., Watson, M. L., Ford, M. J., Munro, J. F., Stodolant, M. C. & Campbell, D. B. (1977). Plasma fenfluramine levels, weight loss and side effects. British Medical Journal ii, 1322–1325.CrossRefGoogle Scholar
LeDouarec, J. D., Schmitt, H. & Laubie, M. (1966). Etude pharmacologique de la fenfluramine et de ses isomères optiques. Archives Internationales de Pharmacodynamie et de Thérapie 161, 206–232.Google Scholar
Liddle, R. A., Morita, E. T., Conrad, C. K. & Williams, J. A. (1986). Regulation of gastric emptying in humans by cholecystokinin. Journal of Clinical Investigations 77, 992996.CrossRefGoogle ScholarPubMed
Mottram, D. R. & Patel, R. J. (1979). Peripheral effects of fenfluramine mediated via the release of 5-hydroxytryptamine. General Pharmacology 10, 441444.CrossRefGoogle ScholarPubMed
Pollock, J. D. & Rowland, N. (1981). Peripherally administered serotonin decreases food intake in rats. Pharmacology, Biochemistry and Behaviour 15, 179–183.CrossRefGoogle ScholarPubMed
Rees, W. R., Clark, R. A., Holdsworth, C. D., Barber, D. C. & Howlett, P. J. (1980). The effect of β-adenoreceptor agonists and antagonists on gastric emptying in man. British Journal of Clinical Pharmacology 10, 551–554.CrossRefGoogle Scholar
Richardson, B. P. & Engel, G. (1986). The pharmacology and function of 5-HT3 receptors. TINS 9, 424–428.Google Scholar
Robinson, P. H., Moran, T. H. & McHugh, P. R. (1986). The inhibition of gastric emptying and feeding in fenfluramine. American Journal of Physiology 250, R764–R799.Google ScholarPubMed
Rowland, N. E. & Carlton, J. (1984). Inhibition of gastric emptying by peripheral and central fenfluramine in rats: correlation with anorexia. Life Sciences 34, 2495–2499.CrossRefGoogle ScholarPubMed
Rowland, N. E. & Carlton, J. (1986 a). Tolerance to fenfluramine anorxia: fact or fiction? Appetite 7, Suppl., 71–83.CrossRefGoogle ScholarPubMed
Rowland, N. E. & Carlton, J. (1986 b). Neurobiology of an anorectic drug: fenfluramine. Progress in Neurobiology 27, 13–62.CrossRefGoogle ScholarPubMed
Rowland, N. E. & Carlton, J. (1986 c). Effects of fenfluramine on food intake, body weight, gastric emptying and brain monoamines in Syrian hamsters. Brain Research Bulletin 17, 575–581.CrossRefGoogle ScholarPubMed
Stunkard, A. J. (1981). Anorectic agents: a theory of action and lack of tolerance in a clinical trial. In Anorectic Agents: Mechanisms of Action and Tolerance, pp. 191–209 [Garattini, S. and Samanin, R., editors]. New York: Raven Press.Google Scholar