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Serotonin Drugs and the Treatment of Obesity

  • Chapter
Obesity: Pathology and Therapy

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 149))

Abstract

The monoamine neurotransmitter, serotonin (5-HT, 5-hydroxytryptamine) was first linked to the control of food intake, and of feeding behavior, more than 20 years ago. Early studies showed that increasing CNS 5-HT levels by using 5-HT precursors such as tryptophan and 5-hydroxytryptophan (5-HTP) produced a significant reduction in the food intake of laboratory animals. Increasing 5-HT activity by other mechanisms such as directly administering 5-HT into the CNS, blocking synaptic 5-HT breakdown or directly stimulating (agonising) 5-HT receptors also produced this hypophagic response (BRAY a n d YORK 1 9 7 2 ; JESPERSON a n d SCHEEL-KRUGER 1973; BARRETT a n d MCSHERRY 1975; PINDER 1975; GARATTINI and SAMANI, 1976). Moreover, it was noted that neurotoxic lessioning of 5-HT neurons (with 5,7-dihyroxytrytamine, 5,7-DHT), or preventing 5-HT synthesis (using para-chlorophenylanine, pCPA) which depletes neuronal 5-HT, not only prevented 5-HT induced hypophagia but increased food intake (MACKENZIE et al. 1979).

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References

  • Allison DB, Kaprio J, Korkeila M, Koskenvuo M, Neale MC, Hayakawa K (1996) The heritability of body mass index among an international sample of monozygotic twins reared apart. Int J Obesity 20:501–506

    CAS  Google Scholar 

  • Anderson IM, Parry-Billins M, Newsholme EA, Fairburn CG, Cowen PJ (1990) Dieting reduced plasma tryptophan and alters brain 5-HT functioning in women. Psychological Medicine 20:785–791

    PubMed  CAS  Google Scholar 

  • Antin J, Gibbs J, Holt J Young RC, Smith GP (1975) Cholecystokinin elicits the complete behavioral sequence of satiety in rats. J Comp Physiol Psych 89:784–760

    CAS  Google Scholar 

  • Ashley DVM, Fleury MO, Golay A, Maeder E, Leathwood PD (1985) Evidence for diminished brain 5-HT biosynthesis in obese diabetic humans. Am J Clin Nutr 42:1240–1245

    PubMed  CAS  Google Scholar 

  • Aulukh CS, Mazzola-Pomietto P, Hilihan-Giblin BA, Murphy DL (1995) Lack of cross tolerance for hypophagia induced by DOI verses mCPP suggests separate mediation by 5-HT2A and 5-HT2C receptors respectively. Neuropsychopharmaocology 13:1–8

    Google Scholar 

  • Aulukh CS, Mazzola-Pomietto P, Wozniak, KM, Hill JL, Murphy DL (1994) l-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane-induced hypophagia and hyperthermia in rat is mediated by serotonin-2A receptors. J Pharm Exp Ther 270:127–152

    Google Scholar 

  • Barrett AM, McSherry L (1975) Inhibition of drug-induced anorexia in rats by methysergide. J Pharm Pharmacol 27:889–895

    PubMed  CAS  Google Scholar 

  • Blundell JE (1977) Is there a role for serotonin (5-hydroxytryptamine) in feeding? Int J Obes 1:15–42

    PubMed  CAS  Google Scholar 

  • Blundell JE (1983) Problems and processes underlying the control of food selection and nutrient intake. In: Wurtman RJ, Wurtman JJ (eds) Nutrition and the Brain, Raven Press, NY, pp 163–222

    Google Scholar 

  • Blundell JE, Hill AJ (1985) Effects of dexfenfluramine in feeding and body weight Relationship with food consumption and palatability. In: Vague J, Guy-Grand B, Bjontroup P (eds) Metabolic complication of human obesities. Elservier, Nordlolland pp 199–206

    Google Scholar 

  • Blundell JE, Hill AJ (1987) Nutrition, serotonin and appetite: Case study in the evaluation of a scientific idea. Appetite 8:183–194

    PubMed  CAS  Google Scholar 

  • Blundell JE, Hill AJ (1988) On the mechanism of action of dexfenfluramine: Effect on alliesthesia and appetite motivation in lean and obese subjects. Clin Neuropharmacol 11(S)121–134

    Google Scholar 

  • Blundell JE, Hill AJ (1989) Do serotoninergic drugs decrease energy intake by reducing fat or carbohydrate intake? Effects of d-fenfluramine with supplemented weight increase diets. Pharmacol Biochem Behav 31:773–778

    Google Scholar 

  • Blundell JE, Latham CJ (1978) Pharmacological manipulation of feeding behavior: possible influences of serotonin and dopamine on food intake. In: Garattini S, Samanin R (eds) Central mechanisms of anorectic drugs. Raven Press, NY, pp 83–109

    Google Scholar 

  • Blundell JE, Latham CJ (1979) Serotoninergic influences on food intake: 5-hydroxytryptophan on parameter of feeding behavior in deprived and freefeeding rats. Pharmacol Biochem Behav 11:431–437

    PubMed  CAS  Google Scholar 

  • Blundell JE, Latham CJ (1980) Characterisation of adjustments to the structure of feeding behaviour following pharmacological treatment: effects of amphetamine and fenfluramine and the antagonism produced by pimozide and methergoline. Pharmacol Biochem Behav 12:717–722

    PubMed  CAS  Google Scholar 

  • Blundell JE, Lawton CL (1995) Serotonin and dietary fat intake: effects of dexfenfluramine. Met Clin Exper 44:33–37

    CAS  Google Scholar 

  • Blundell JE, Lawton CL, Halford JCG (1995) Serotonin, eating behavior and fat intake. Obes Res 3(4S)471–476

    Google Scholar 

  • Blundell JE, MacDiarmid JI (1997) Passive overconsumption: fat intake and short-term energy balance. Annals of the New York Acadamy of Sciences 827:392–407

    CAS  Google Scholar 

  • Blundell JE, McArthur RA (1981) Behavioral flux and feeding: continuous monitoring of food intake and food selection, and the video-recording of appetitive and satiety sequences for the analysis of drug action. In: SamanIn R, Garattini S (eds) Anorectic agents: mechanisms of action and tolerance. Raven, NY, pp 19–43

    Google Scholar 

  • Boeles S, Williams C, Campling GM, Goodall EM, Cowen PJ (1997) Sumatriptan decreases food intake and increase plasma growth hormone in healthy women. Psychopharmacology 129:179–182

    PubMed  CAS  Google Scholar 

  • Bouchard C (1989) Genetic factors in obesity. Medical Clinics of North America 73:67–81

    PubMed  CAS  Google Scholar 

  • Bouchard C (1991) Heredity and the path to overweight and obesity. Medicine and Science of Sports Exercise 23:285–291

    CAS  Google Scholar 

  • Bradley Nomenclature Committee (1986) Proposals for classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology 25:563–576

    Google Scholar 

  • Bray GA, York DA (1972) Studies on food intake of genetically obese rats. Am J Physiol 233:176–179

    Google Scholar 

  • Brewerton TD (1995) Toward a unified theory of serotonin dysregulation in eating related disorders. Psychoneuroendocrinology 20:561–590

    PubMed  CAS  Google Scholar 

  • Brezinski AA, Wurtman JJ, Wurtman RJ (1990) D-fenfluramine suppresses the increased caloric and carbohydrate intakes and improves the mood of women with pre-menstrual tension. Obestet Gynecol 76:296–301

    Google Scholar 

  • Caccia S, Bizzi A, Coltro G, Francasso C, Frittoli E, Mennini T, Garattini S (1992) Anorectic activity of fluoxetine and norfluoxetine in rats: Relationship between brain concentrations and in-vitro potencies on monoaminergic mechanisms. J Pharm Pharmacol 44:250–254

    PubMed  CAS  Google Scholar 

  • Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P (1995) Recombinant mouse on protein: Evidence for a peripheral signal linking adiposity and central neural networks. Science 269:546–549

    PubMed  CAS  Google Scholar 

  • Cangiano C, Ceci F, Casinco A, Del Ben M, Lavino A, Mauscatioli M, Antonucci F, Rossi-Fanelli F (1992) Eating behavior and adherence to dietary prescription in obese adult subjects treated with 5-hydroxytryptophan. Am J Clin Nutr 56:863–867

    PubMed  CAS  Google Scholar 

  • Clifton PG (1994) The neuropharmacology of meal patterning. In: Cooper SJ (ed) Ethology and Psychopharmacology. Wiley, Chichester, pp 313–328

    Google Scholar 

  • Clifton PG, Barnfield AM, Philcox L (1989) A behavioral profile of fluoxetine induced anorexia. Psychopharmacology 107:89–95

    Google Scholar 

  • Clineschimdt BV, McGuffen JC, Pfleuger AB, Totaro JA (1978) A 5-hydroxytryptamine-like mode of action for 6-chloro-2-[l-piperazinyl]-pyrazine (MK-212). Br J Pharmacol 62:579–589

    Google Scholar 

  • Coscina DV, Feifel D, Nobrega JN, Currie G (1994) Intra ventricular but not intra paraventricular nucleus metergoline elicits feeding in satiated rats. Am J Physiol 266:1562–1567

    Google Scholar 

  • Cowen PJ, Clifford EM, Walsh AE, Williams C, Fairburn CG (1996) Moderate dieting causes 5-HT2C supersensitization. Psychological Medicine 26:1156–1159

    Google Scholar 

  • Currie PJ, Coscina DV (1996) Metergoline potentiates natural feeding and antagonizes the anorectic action of medial hypothalamic 5-HT. Pharmacol Biochem Behav 53:1023–1028

    PubMed  CAS  Google Scholar 

  • Curzon G (1990) Serotonin and appetite. Ann NY Acad Sci 600:521–530

    PubMed  CAS  Google Scholar 

  • Curzon G (1991) Effects of tryptophan and 5-hydroxytryptamine receptor subtype agonists on feeding. Adv Exp Med Biol 294:377–388

    PubMed  CAS  Google Scholar 

  • Curzon G, Gibson El, Oluyomi AO (1997) Appetite suppression by commonly used drugs depends on 5-HT receptors but not on 5-HT availability. Trends Pharmacol Sci 18:21–25

    PubMed  CAS  Google Scholar 

  • Dourish CT (1995) Multiple serotonin receptors: Opportunities for new treatments for obesity. Obesity Res 3(s4):449–462

    Google Scholar 

  • Drewnowski A, Kurth C, Holden-Wiltse J, Saari J (1992) Food preference in human obesity: Carbohydrates verses fat. Appetite 18:207–221

    PubMed  CAS  Google Scholar 

  • Dryden S, Frankish HM, Wang Q, Pickavance L, Williams G (1996a) The serotoninergic agent fluoxetine reduces neuropeptide Y levels and neuropeptide Y secretion in the hypothalamus of lean and obese rats. Neuroscience 72:557–566

    PubMed  CAS  Google Scholar 

  • Dryden S, Frankish HM, Wang Q, Williams G (1996b) Increased feeding and neuropeptide Y (NPY) but not NPY mRNA levels in hypothalamus of the rat following central administration of the serotonin synthesis inhibitor p-chlorophenylalinine. Brain Research 724:232–237

    PubMed  CAS  Google Scholar 

  • Dryden S, Wang Q, Frankish HM, Williams G (1996c) Differential effects of the 5-HT1B/2C receptor agonist mCPP and the 5-HTIA agonist flesinoxan on hypothalamic neuropeptide Y in the rat: evidence that NPY may mediate serotonin’s effects on food intake. Peptides 17:943–949

    PubMed  CAS  Google Scholar 

  • Dryden S, Williams G (1996) The role hypothalamic peptides in the control of energy balance and body weight. Curr Opin Endocrin Diab 3:51–58

    CAS  Google Scholar 

  • Fernstorm JD, Wurtman RJ (1973) Control of brain 5-HT content by dietary carbohydrates. In: Barchas J, Usdin E (eds) Serotonin and behavior. Academic Press, NY, pp 121-128

    Google Scholar 

  • Finer N, Finer S, Nauova RP (1992) Drug therapy after very-low-calorie diets. Am J Clin Nutr 1955-85

    Google Scholar 

  • Fisler JS, Underberger SJ, York DA, Bray GA (1993) D-Fenfluramine in a rat model of dietary fat-induced obesity. Pharmacol Biochem Behav 45:487–493

    PubMed  CAS  Google Scholar 

  • Fletcher PJ, Coscina DV (1993) Injecting 5-HT into the PVN does not prevent feeding induced by 8-OH-DPAT into the raphe. Pharmacol Biochem Behav 46:487–491

    PubMed  CAS  Google Scholar 

  • Gaddam JH, Picarelli ZP (1957) Two kind of tryptamine receptor. Br J Pharmaco 12:323–328

    Google Scholar 

  • Garattini S, Samanin R (1976) Anorectic drugs and brain neurotransmitters. In: Silverstone T (ed) Food intake and appetite. Dahlem Konferenzen, Berlin, pp 82–208

    Google Scholar 

  • Gibson EL, Kennedy AJ, Curzon G (1993) D-Fenfluramine- and D-norfenfluramineinduced hypophagia: differential mechanisms and involvement of postsynaptic 5-HT receptors. Euro J Pharmacol 242:83–90

    CAS  Google Scholar 

  • Goodall EM, Cowen PJ, Franklin M, Silverstone T (1993) Ritanserin attenuates anorectic endocrine and thermic responses to d-fenfluramine in human volunteers. Psychopharmacology 112:461–466

    PubMed  CAS  Google Scholar 

  • Goodall EM, Silverstone T (1988) Differential effect of D-fenfluramine and metergoline on food intake in human subjects. Appetite 11:215–228

    PubMed  CAS  Google Scholar 

  • Goodwin GM, Cowen PJ, Fairburn CJ, Parry-Billings M, Calder PC, Newsholme EA (1990) Plasma concentrations of tryptophan and dieting. Brit Med J 17:839–842

    Google Scholar 

  • Goodwin GM, Fairburn CG, Cowen PJ (1987) Dieting changes 5-HT function in women but not in men, implications for the aetiology of anorexia nervosa? Psychol Med 17:839–842

    PubMed  CAS  Google Scholar 

  • Green S, Lawton CL, Wales JK, Blundell JE (1997) Risk factors for overeating: Dex-fenfluramine suppresses the intake of sweet high fat or carbohydrate food in obese women. Int J Obesity 21(3)s64

    Google Scholar 

  • Greeno CA, Wing R (1996) A double-blind, placebo-controlled trial of the effect of fluoxetine on dietary intake in overweight women with and without binge-eating disorder. Am J Clin Nutr 64:267–273

    PubMed  CAS  Google Scholar 

  • Grignaschi G, Sironi F, Samanin R (1995) The 5-HT1B receptor mediates the effect of d-fenfluramine one eating caused by intra-hypothalamic injection of neuropeptide Y. Euro J Pharmacol 274:221–224

    CAS  Google Scholar 

  • Grignaschi G, Samanin R (1992) Role of serotonin and catecholamines in brain feeding suppressant effects of fluoxetine. Neuropharmacology 31:445–449

    PubMed  CAS  Google Scholar 

  • Guy-Grand B (1992) Clinical studies with d-fenfluramine. Am J Clin Nutr 56:173–176

    Google Scholar 

  • Halaas JL, Gajiwala KD, Maffie M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM (1995) Weight reducing effects of a plasma protein encoded by the obese gene. Science 269:543–546

    PubMed  CAS  Google Scholar 

  • Halford JCG, Blundell JE (1993) 5-Hydroxytryptaminergic drugs compared on the behavioral sequence associated with satiety. Br J Pharmacol 100:p95

    Google Scholar 

  • Halford JCG, Blundell JE (1996a) Metergoline antagonizes fluoxetine induced suppression of food intake but not changes in the behavioral satiety sequence. Pharmacol Biochem Behav 54:745–751

    PubMed  CAS  Google Scholar 

  • Halford JCG, Blundell JE (1996b) The 5-HT1B receptor agonist CP-94,253 reduces food intake and preserves the behavioral satiety sequence. Physiol Behav 60:933–939

    PubMed  CAS  Google Scholar 

  • Halford JCG, Blundell JE (1998) Direct and continuous behavioral analysis for the diagnosis of drug action on feeding. Current Protocols in Neuroscience (in press)

    Google Scholar 

  • Halford JCG, Heal DJ, Blundell JE (1995) effects in the rat of sibutramine on food intake and the behavioral satiety sequence. Br J Pharmacol 144:p387

    Google Scholar 

  • Halford JCG, Lawton CL, Blundell JE (1997) The 5-HT2 receptor agonist MK-212 reduces food intake but disrupts the behavioral satiety sequence. Pharmacol Biochem Behav 56:41–46

    PubMed  CAS  Google Scholar 

  • Halford JCG, Wanninayake SCD, Blundell JE (1998) Behavioral satiety sequence (BSS) for the diagnosis of drug action on food intake. Pharmacol Biochem Behav 61:159–168

    PubMed  CAS  Google Scholar 

  • Hill AJ, Blundell JE (1986) Model system for investigating the actions of anorectic drugs: Effects of D-fenfluramine on food intake, nutrient selection, food preference, meal patterns, hunger and satiety in human subjects. In: Advances in the Bioscience. Pergamon Press, Oxford, pp 377–389

    Google Scholar 

  • Hill A J, Blundell FE (1990) Sensitivity of the appetite control system in obese subjects to nutritional and serotoninergic challenges. Int J Obesity 14:219–233

    CAS  Google Scholar 

  • Hill AJ, Rogers PJ, Blundell JE (1995) Techniques for the experimental measurement of human eating behavior; a practical guide. Int J Obesity 19:361–375

    CAS  Google Scholar 

  • Horton TJ, Drougas H, Brachey A, Reed GW, Hill JO (1995) Fat and carbohydrate overfeeding in humans: different effects on energy storage. Am J Clin Nutr 62:19–29

    PubMed  CAS  Google Scholar 

  • Hoyer D, Martin G (1997) 5-HT receptor classification and nomenclature: Towards a harmonisation with the human genome. Neuropharmacology 36:419–428

    PubMed  CAS  Google Scholar 

  • Hutson PH, Donohoe TP, Curzon G (1988) Infusion of the 5-hydroxytryptamine agonists RU-24969 and TFMPP into the paraventricular nucleus of the hypothalamus. Psychopharmacology 97:550–552

    Google Scholar 

  • Jesperson S, Scheel-Kruger J (1973) Evidence for a difference in mechanism of the action between fenfluramine and amphetamine induced anorexia. J Pharm Pharmacol 22:637–638

    Google Scholar 

  • Jimerson DC, Wolfe BE, Metzger ED, Finkelstein DM, Cooper TB, Levine JM (1997) Decreased serotonin function in bulimia nervosa. Arch Gen Psychiatry 54:529–534

    PubMed  CAS  Google Scholar 

  • Kanarek RB (1987) Neuropharmacological approach to studying diet selection. In: Kaufman S (ed) Amino Acids in Health: New Perspectives. Alan R. Liss, NY, pp 383–401

    Google Scholar 

  • Kennett GA, Dourish CT, Curzon G (1987) 5-HT1B agonists induce anorexia at a post synaptic site. Euro J Pharmacol 141:429–435

    CAS  Google Scholar 

  • Kennett GA, Curzon G (1988a) Evidence that the hypophagia induced by mCPP and TFMPP requires 5-HTl c and 5-HTm receptors; hypophagia induced by RU-24969 only requires 5-HT1B receptors. Psychopharmacology 96:93–100

    PubMed  CAS  Google Scholar 

  • Kennett GA, Curzon G (1988b) Evidence that mCPP may have behavioral effects mediated by central 5-HTl c receptors. Br J Pharmacol 94:137–147

    PubMed  CAS  Google Scholar 

  • Kennett GA, Curzon G (1991) Potencies of antagonists indicate that 5-HTl c receptors mediate l-3(chlorophenyl)piperazine- induced hypophagia. Br J Pharmacol 103: 2016–2020

    PubMed  CAS  Google Scholar 

  • Kennett GA, Wood MD, Glen A, Grewal S, Frobes F, Gadre A, Blackburn TP (1994) In vivo properties of SB 200646 A, a selective 5-HT2C/2B receptor antagonist. Br J Pharmacol 111:797–802

    PubMed  CAS  Google Scholar 

  • Kennett GA, Wood MD, Bright F, Trail B, Riley G, Holland V, Avenel KY, Stean T, Upton N, Bromidge S, Forbes IT, Brown AM, Middledmiss DN, Blackburn TP (1997) SB 242084, a selective and brain potent 5-HT2C receptor. Neuropharmacology 36:609–620

    PubMed  CAS  Google Scholar 

  • King BH, Brazell C, Dourish CT (1989) MK-212 increase rat plasma ACTH concentration by activation of the 5-HTl c receptor subtype. Neuroscience Letters 105:174–176

    PubMed  CAS  Google Scholar 

  • Kitchener SJ, Dourish CT (1994) An examination of the behavioral specificity of hypophagia induced by 5-HT1B, 5-HT1C and 5-HT2 receptor agonists using the post-prandial sequence in rats. Psychopharmacology 113:368–377

    Google Scholar 

  • Koe BK, Nielson JA, Macor JE, Heym J (1992) Biochemical and behavioral studies of the 5-HTIB receptor agonist, CP-94,253. Drug Dev Res 26:241–250

    CAS  Google Scholar 

  • Koe BK, Weissman A, Welch WM, Browne RG (1983) Sertraline, 1S,4S-Nmethyl-4(3,4-dichlorophenyl)-l,2,3,4-tetrahydro-l-naphathylamine, a new uptake inhibitor with selectivity for serotonin. J. Pharmacol Exp Ther 266:686–700

    Google Scholar 

  • Lafreniere F, Lambert J, Rasio E, Serri (1993) Effects of dexfenfluramine treatment on body weight and post-prandial thermogenesis in obese subjects. A double blind placebo-controlled study. Int J Obesity 17:25–30

    CAS  Google Scholar 

  • Lawton CL, Blundell JE (1992) The effects of D-fenfluramine on intake of carbohydrate supplements is influenced by the hydration of test diets. Physiol Behav 53:517–523

    Google Scholar 

  • Lawton CL, Blundell JE (1993) 5-HT manipulation and dietary choice: Variable carbohydrate (Polycose) suppression demonstrated only under specific experimental conditions. Psychopharmacology 112:375–382

    PubMed  CAS  Google Scholar 

  • Lawton CL, Wales JK, Hill AJ, Blundell JE (1995) Serotoninergic manipulation, mealinduced satiety and eating patterns. Obesity Research 3:345–356

    PubMed  CAS  Google Scholar 

  • Lee MD, Clifton PG (1992) Partial reversal of fluoxetine anorexia by the 5-HT antagonist metergoline. Psychopharmacology 107:359–364

    PubMed  CAS  Google Scholar 

  • Leibowitz SF (1980) Neurochemical systems of the hypothalamus - control of feeding and drinking behavior and water-electrolyte excretion. In: Morgane PJ, Panksepp J (eds) Handbook of the hypothalamus (vol VI, Part A). Marcel Decker, New York, pp 299–437

    Google Scholar 

  • Leibowitz SF, Alexander JT, Cheung WK, Weiss GF (1992) Effects of serotonin and serotonin blocker metergoline on meal patterns macronutrient selection. Pharmacol Biochem Behav 45:185–194

    Google Scholar 

  • Leibowitz SF, Hammer NJ, Chang K (1981) Hypothalamic paraventricular nucleus lesions produce overeating in the rat. Physiol Behav 27:1031–1040

    PubMed  CAS  Google Scholar 

  • Leibowitz SF, Shor-Posner G (1986) Brain serotonin and eating behavior. Appetite 7S:1–14

    Google Scholar 

  • Leibowitz SF, Weiss GF, Suh JN (1990) Medial hypothalamic nuclei mediate serotonin’s inhibitory effect on feeding behavior. Pharmacol Biochem Behav 37:735–742

    PubMed  CAS  Google Scholar 

  • Leibowitz SF, Weiss GF, Walsh UA, Viswanath D (1989) Medial hypothalamic serotonin: role in circadian patterns of feeding and macronutrient selection. Brain Res 503:132–140

    PubMed  CAS  Google Scholar 

  • Lentus K-U, Hinney A, Ziegler K, Rosenkranz K, Wurmser H, Barth N, Jacob K, Comer H, Mayer H, Grzeschik K-H, Schafer H, Remschmidt H, Pirke KM, Hebebrand J (1997) Evaluation of CYS23SER mutation within the human 5-HT2C receptor gene: No evidence for an association of the mutant allele with obesity or underweight in children, adolescents and young adults. Life Sciences 61(1)9–16

    Google Scholar 

  • Lightowler S, Kennett GA, Wood MD, Brown AM, Glen A, Blackburn TP, Tulloch IF (1994) Hypophagic effect of fluoxetine in rats is not mediated by inhibition of 5-HT re-uptake or an agonist action at 5-HT2C receptors. Br J Pharmacol 112:359–364

    Google Scholar 

  • Lightowler S, Wood M, Brown T, Glen A, Blackburn T, Tulloch I, Kennett G (1996) An investigation of the mechanism responsible for fluoxetine-induced hypophagia in rats. Euro J Pharmacol 296:137–143

    CAS  Google Scholar 

  • Lucki I, Kreider MS, Simansky KJ (1988) Reduction of feeding behavior by the serotonin uptake inhibitor sertraline. Psychopharmacology 96:289–295

    PubMed  CAS  Google Scholar 

  • Luo S, Li ETS (1990) Food intake and selection pattern of rats treated with dexfenfluramine, fluoxetine and RU-24969. Brain Res Bull 24:729–733

    PubMed  CAS  Google Scholar 

  • MacDiaramid JI, Cade JE, Blundell JE (1997) High and low fat consumers, their macronutrient intake and body mass index: Further analysis of the National Diet Survey of British Adults. Euro J Clin Nutr 50:505–512

    Google Scholar 

  • MacKenzie RG, Hoebel BG, Ducret RP, Trulson ME (1979) Hyperphagia following intraventricular p-chlorophenylalanine-, leucine- or tryptophan-methyl esters: lack of correlation with whole brain serotonin level. Pharmacol Biochem Behav 10:951–955

    PubMed  CAS  Google Scholar 

  • McGuirk J, Muscat R, Willner P (1992) Effects of the 5-HT uptake inhibitors femoxetine and paroxetine, and the 5-HT1A agonist eltoprazine, on the behavioral satiety sequence. Pharmacol Biochem Behav 41:801–805

    PubMed  CAS  Google Scholar 

  • McGuirk J, Silverstone T (1990) The effect of 5-HT re-uptake inhibitor fluoxetine on food intake and body weight in healthy male subjects. Int J Obesity 14:361–372

    CAS  Google Scholar 

  • Macor JE, Burkhart CA, Heym JH, Ives JL, Lebel LA, Newmand ME, Nielsen JA, Ryan K, Schulz DW, Torgersen LK, Koe BK (1990) 3-(l,2,5,6-Tetrahydropyrid-4-yl)pyrrolo [3,2-b]pyrid-5-one; a potent and selective 5-HT1B agonist and rotationally restricted phenolic analogue of 5-methoxy-3-(l,2,5,6-tetrahydropyrid-4-yl)indole. J Med Chem 33:2087–2093

    PubMed  CAS  Google Scholar 

  • Neill JC, Cooper SJ (1989) Evidence that d-fenfluramine anorexia is mediated by 5-HTi receptors. Psychopharmacology 97:213–218

    PubMed  CAS  Google Scholar 

  • Neill JC, Bendotti C, Samanin R (1990) Studies on the role of 5-HT receptors in satiation and the effect of d-fenfluramine in the runway test. Eur J Pharmacol 190:105–112

    PubMed  CAS  Google Scholar 

  • Oluyomi AO, Gibson EL, Barnfield AM, Curzon G (1994) D-Fenfluramine and Dnorfenfluramine hypophagias do not require increased hypothalamic 5-hydroxytryptamine release. Euro J Pharmacol 264:111–115

    CAS  Google Scholar 

  • Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F (1995) Effects of the obese gene product on weight regulation and in ob/ob mice. Science 269:540–543

    PubMed  CAS  Google Scholar 

  • Peroutka SJ, Snyder SH (1979) Multiple serotonin receptors: different binding of 3H-5-hydroxytryptamine, 3H-lysergic acid diethylamide and 3H-spiroperidol. Mol Pharmacol 16:687–699

    PubMed  CAS  Google Scholar 

  • Pinder BM, Brogden RN, Sawyer PR, Speight TM, Avery GS (1975) Fenfluramine: A review of the pharmacological properties and therapeutic in obesity. Drugs 10:241–323

    PubMed  CAS  Google Scholar 

  • Pirke KM, Schweiger U, Laessle RG (1986) Effects on diet composition on affective state in anorexia nervosa and bulimia. Clin Neuropharmacol 9:561–590

    Google Scholar 

  • Poppitt SD, Prentice AM (1996) Energy density and its role in the control of food intake: Evidence from metabolic and community studies. Appetite 26:153–174

    PubMed  CAS  Google Scholar 

  • Prats E, Monfar M, Castell J, Iglesias R, Allemany M (1989) Energy intake of rats fed a cafeteria diet. Physiol Behav 45:2263–2272

    Google Scholar 

  • Raiteri M, Bonanno G, Vallebouona F (1995) In vitro and in vivo effects Dfenfluramine: no apparent relationship between 5-hydroxytryptamine release and hypophagia. J Pharmacol Exp Ther 273:643–649

    PubMed  CAS  Google Scholar 

  • Ravussin E, Valencia ME, Esparza J, Bennett PH, Schulz LO (1994) Effects of a traditional lifestyle on obesity in Pima Indians. Diabetes Care 17:1067–1074

    PubMed  CAS  Google Scholar 

  • Rogers PJ, Blundell JE (1984) Meal patterns and food selection during the development of obesity in rats fed a cafeteria diet. Neuroscience Biobeh Rev 8:441–453

    CAS  Google Scholar 

  • Samanin R, Mennini T, Bendotti C, Barone D, Caccia S, Garattini S (1989) Evidence that central 5-HT2 receptors do not play an important role in anorectic activity of d-fenfluramine in the rat. Neuropharmacology 28:465–469

    PubMed  CAS  Google Scholar 

  • Sclafani A (1984) Animal models of obesity: Classification and characterisation. Int J Obes 8:491–508

    PubMed  CAS  Google Scholar 

  • Simansky KJ, Viadya AH (1990) Behavioral mechanisms for the anorectic actions of the serotonin (5-HT) uptake inhibitor sertraline in rats: comparison with directly acting agonists. Brain Res Bull 25:953–960

    PubMed  CAS  Google Scholar 

  • Sørensen TIA, Price RA, Stunkard AJ, Schulsinger F (1989) Genetics of obesity in adult adoptees and their biological siblings. Brit Med J 298:87–90

    Google Scholar 

  • Spitzer RL, Devlin M, Walsh BT, Hasin D, Wing RR, Marcus MD, Stunkard AJ, Wadden S, Arga S, Mitchell J, Monas C (1992) Binge eating disorder: A multisite field study of diagnostic criteria. Int J Eating Disorder 11:191–203

    Google Scholar 

  • Stunkard AJ (1959) Eating patterns in obesity. Psychiatric Quarterly 33:284–292

    PubMed  CAS  Google Scholar 

  • Stunkard AJ, Berkowitz R, Tratikut C, Reiss E, Young L (1996) D-Fenfluramine treatment of binge eating disorder. Am J Psychiatry 153:1455–1459

    PubMed  CAS  Google Scholar 

  • Tecott LH, Sun LM, Akana SF, Lowenstien DH, Dallman MF, Julius D (1995) Eating disorder and epilepsy in mice lacking 5-HT2C serotonin receptors. Nature 374:542–546

    PubMed  CAS  Google Scholar 

  • Teff KL, Young SN, Blundell JE (1989) The effect of protein or carbohydrate breakfasts on subsequent plasma amino acid levels, satiety and nutrient selection in normal males. Pharmacol Biochem Behav 34:410–417

    Google Scholar 

  • Wadden TA, Bartlett SJ, Foster GD, Greenstein RA, Wingate BJ, Stunkard AJ, Letizia (1995) Sertraline and relapse prevention following treatment by a very low calorie diet: a controlled clinical trial. Obesity Res 3:549–557

    CAS  Google Scholar 

  • Walsh AE, Oldman AD, Franklin M, Fairburn CG, Cowen PJ (1995) Dieting decreases plasma tryptophan and increases the prolactin response to D-fenfluramine in women but not men. J Affective Disorders 33:89–97

    CAS  Google Scholar 

  • Walsh AE, Smith KA, Oldman AD, Williams C, Goodall EM, Cowen PJ (1994) m-Chlorophenylpiperazine decrease food intake in a test meal. Psychopharmacology 116:120–122

    PubMed  CAS  Google Scholar 

  • Wong DT, Reid LR, Threlkeld PG (1988) Suppression of food intake in rats by fluoxetine: Comparison of anantiomers and effects of serotonin antagonists. Pharmacol Biochem Behav 31:475–479

    PubMed  CAS  Google Scholar 

  • Wurtman J J, Wurtman RJ (1977a) Drugs that enhance central serotoninergic transmission diminish elective carbohydrate consumption by rats. Life Science 24:895–904

    Google Scholar 

  • Wurtman J J, Wurtman RJ (1977b) Fenfluramine and fluoxetine spare protein consumption while suppressing caloric intake by rats. Science 198:1178–1180

    PubMed  CAS  Google Scholar 

  • Wurtman JJ, Wurtman RJ, Marks S et al (1985) D-fenfluramine selectively suppresses carbohydrate snaking by obese subjects. Int J Eating Disorders 4:89–99

    CAS  Google Scholar 

  • Wurtman J J, Wurtman RJ Reynolds S et al (1987) Fenfluramine suppresses snack intake among carbohydrate cravers but not among noncarbohydrate cravers. Int J Eating Disorders 6:687–699

    Google Scholar 

  • Wurtman RJ, Fernstorm JD (1974) Effects of diet on brain neurotransmitters. Nutr Review 32:193–200

    CAS  Google Scholar 

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Authors
  1. J. C. G. Halford
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  2. J. E. Blundell
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Editors and Affiliations

  1. Department of Clinical Research, Parke-Davis Pharmaceutical Research, Division of Warner Lambert Company, 2800 Plymouth Road, Ann Arbor, MI, 48105, USA

    Dean H. Lockwood M.D. (Vice President) (Vice President)

  2. Neuroscience Therapeutics, Parke-Davis Pharmaceutical Research, Division of Warner Lambert Company, 2800 Plymouth Road, Ann Arbor, MI, 48105, USA

    Thomas C. Heffner Ph.D. (Sr. Director) (Sr. Director)

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Halford, J.C.G., Blundell, J.E. (2000). Serotonin Drugs and the Treatment of Obesity. In: Lockwood, D.H., Heffner, T.C. (eds) Obesity: Pathology and Therapy. Handbook of Experimental Pharmacology, vol 149. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59651-3_7

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  • DOI: https://doi.org/10.1007/978-3-642-59651-3_7

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