Abstract
The role of serotonin (5-HT) in appetite control is well recognised. 5-HT drugs reduce food intake in rodents in a manner consistent with an enhancement of satiety. In humans, they have been shown to reduce caloric intake, an effect associated with reduced hunger and increased satiety. These effects appear to be mediated, at least in part, by the 5-HT2C receptor subtype. 5-HT-acting drugs such as fenfluramine, d-fenfluramine, and sibutramine have provided effective anti-obesity treatments in the past. However, more selective agents are needed that produce the same changes in eating behaviour and induce weight loss without unacceptable side effects. Lorcaserin, a selective 5-HT2C receptor agonist, is a novel anti-obesity agent that reduces both energy intake and body weight. The effects of lorcaserin on eating behaviour remain to be characterised as does its behavioural specificity.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abeniam L, Moride Y, Brenot F et al (1996) Appetite suppressant drugs and the risk of primary pulmonary hypertension. N Engl J Med 335:609–616
Arterburn DE, Crane PK, Veenstra DL (2004) The efficacy and safety of sibutramine for weight loss: a systematic review. Arch Intern Med 164:994–1003
Bjenning C, Williams J, Whelan K et al (2004) Chronic oral administration of APD356 significantly reduces body weight and fat mass in obesity-prone (DIO) male and female rats. Int J Obes 28(suppl 1):214
Blundell JE (1977) Is there a role for serotonin (5-hydroxytryptamine) in feeding? Int J Obes 1:15–42
Blundell JE, Halford JCG (1998) Serotonin and appetite regulation: implications for the treatment of obesity. CNS Drugs 9:473–495
Blundell JE, Hill AJ (1990) Sensitivity of the appetite control system in obese subjects to nutritional and serotoninergic challenges. Int J Obes 14:219–233
Blundell JE, Latham CJ (1978) Pharmacological manipulation of feeding behaviour: possible influences of serotonin and dopamine on food intake. In: Garattini S, Samanin R (eds) Central mechanisms of anorectic drugs. Raven, NY, pp 83–109
Blundell JE, Latham CJ (1980) Characteristic adjustments to the structure of feeding behaviour following pharmacological treatments: effects of amphetamine and fenfluramine and the antagonism by pimozide and metergoline. Pharmacol Biochem Behav 12:717–722
Blundell JE, McArthur RA (1981) Behavioural 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
Chapelot D, Mamonier C, Thomas F et al (2000) Modalities of the food intake-reducing effect of sibutramine in humans. Physiol Behav 68:299–308
Clifton PG (1994) The neuropharmacology of meal patterning. In: Cooper SJ (ed) Ethology and psychopharmacology. Wiley, Chichester, pp 313–328
Cowen PJ, Sargent PA, Williams C et al (1995) Hypophagic, endocrine and subjective responses to m-chlorophenylpiperazine in healthy men and women. Hum Psychopharmacol 10:385–391
Goodall E, Silverstone T (1988) Differential effect of d-fenfluramine and metergoline on food intake in human subjects. Appetite 11:215–288
Haddock CK, Poston WSC, Dill PL et al (2002) Pharmacotherapy for obesity: a quantitative analysis of four decades of published randomized clinical trials. Int J Obes 26:262–273
Halford JCG, Blundell JE (1993) 5-Hydroxytryptaminergic drugs compared on the behavioural sequence associated with satiety. Br J Pharmacol 100:95
Halford JCG, Boyland EJ, Cooper SJ et al (2010a) The effects of sibutramine on the microstructure of eating behaviour and energy expenditure in obese women. J Psychopharmacol 24:99–109
Halford JCG, Boyland EJ, Blundell JE et al (2010b) Pharmacological management of human appetite expression: evaluating the effects of novel anti-obesity agents on eating behaviour. Nat Endocrine Rev 6:255–269
Halford JCG, Harrold JA, Boyland EJ, Lawton CL, Blundell JE (2007) Serotonergic drugs: effects on appetite expression and use for the treatment of obesity. Drugs 67:27–55
Halford JCG, Blundell JE (2000) Separate systems for serotonin and leptin in appetite control. Ann Med 32:222–232
Halford JCG, Wanninayake SCD, Blundell JE (1998) Behavioural satiety sequence (BSS) for the diagnosis of drug action on food intake. Pharmacol Biochem Behav 61:159–168
Hansen DL, Toubro S, Stock MJ et al (1998) Thermogenic effects of sibutramine in humans. Am J Clin Nutr 68:1180–1186
Hayashi A, Sonoda R, Kimura Y et al (2004) Antiobesity effect of YM348, a novel 5-HT2C receptor agonist, in Zucker rats. Brain Res 1011:221–227
Heisler LK, Cowley MA, Tecott LH et al (2002) Activation of Central Melanocortin pathways by Fenfluramine. Science 297:609–611
Heisler LK, Cowley MA, Kishi T et al (2003) Central serotonin and melanocortin pathways regulating energy homeostasis. N Y Acad Sci 994:169–174
Heisler LK, Jobst EE, Sutton GM et al (2006) Serotonin reciprocally regulates melanocortin neurons to modulate food intake. Neuron 51:239–249
Hewitt KN, Lee MD, Dourish CT et al (2002) Serotonin 2C receptor agonists and the behavioural satiety sequence in mice. Pharmacol Biochem Behav 71:691–700
Higgs S, Cooper AJ, Barnes NM (2011) Reversal of sibutramine-induced anorexia with a selective 5-HT2C receptor antagonist. Psychopharmacology 214:941–947
Hoyer D, Martin G (1997) 5-HT receptor classification and nomenclature: towards a harmonization with the human genome. Neuropharmacology 36:419–428
James WP, Caterson ID, Coutinho W, Finer N, Van Gaal LF, Maggioni AP, Torp-Pedersen C, Sharma AM, Shepherd GM, Rode RA, Renz CL, SCOUT Investigators (2010) Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med 363:905–917
Kennett GA, Curzon G (1988a) Evidence that the hypophagia induced by mCPP and TFMPP requires 5-HT1C and 5-HT1B receptors; hypophagia induced by RU-24969 only requires 5-HT1B receptors. Psychopharmacology 96:93–100
Kennett GA, Curzon G (1988b) Evidence that mCPP may have behavioural effects mediated by central 5-HT1C receptors. Br J Pharmacol 94:137–147
Kitchener SJ, Dourish CT (1994) An examination of the behavioural 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
Lawton CL, Wales JK, Hill AJ et al (1995) Serotoninergic manipulation, meal-induced satiety and eating patterns. Obes Res 3:345–356
Martin CK, Redman LM, Zhang J et al (2011) Lorcaserin, a 5-HT2C receptor agonist, reduced body weight by decreasing energy intake within influencing energy expenditure. J Clin Endocrinol Metab 96:837–45
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 Obes 14:361–372
Nonogaki K, Abdullah L, Goulding EH et al (2003) Hyperactivity and reduced energy cost of physical activity in serotonin 5-HT2C receptor mutant mice. Diabetes 52:315–320
Padwal R, Li SK, Lau DCW (2003) Long-term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials. Int J Obes 27:1437–46
Pijl H, Koppeschaar HPF, Willekens FLA et al (1991) Effect of serotonin re-uptake inhibition by fluoxetine on body weight and spontaneous food choice in obesity. Int J Obes 15:237–242
Rogers PJ, Blundell JE (1979) Effect of anorexic drugs on food intake and the micro-structure of eating in human subjects. Psychopharmacology 66:159–165
Rolls BJ, Shide DJ, Thorward ML et al (1998) Sibutramine reduces food intake in non-dieting women with obesity. Obes Res 6:1–11
Sargent PA, Sharpley AL, Williams C et al (1997) 5-HT2C receptor activation decreases appetite and body weight in obese subjects. Psychopharmacology 133:309–312
Smith SR, Prosser WA, Donahue DF et al (2009) Lorcaserin (APD356), a selective 5-HT2C agonist, reducing body weight in obese men and women. Obesity 17:494–500
Smith SR, Wiessman NJ, Anderson CM et al (2010) Multicenter, placebo-controlled trial for Lorcaserin for weight management. N Engl J Med 363:245–56
Tecott LH, Sun LM, Akanna SF et al (1995) Eating disorder and epilepsy in mice lacking 5-HT2C serotonin receptors. Nature 374:542–546
Vickers SP, Benwell KR, Porter RH et al (2000) Comparative effects of continuous infusion of mCPP, Ro 60–0175 and d-fenfluramine on food intake, water intake, body weight and locomotor activity in rats. Br J Pharmacol 130:1305–1314
Vickers SP, Clifton PG, Dourish CT et al (1999) Reduced satiating effect of d-fenfluramine in serotonin 5-HT2C receptor mutant mice. Psychopharmacology 143:309–314
Vickers SP, Dourish CT (2004) Serotonin receptor ligands and the treatment of obesity. Curr Opin Investig Drugs 5:377–388
Vickers SP, Dourish CT, Kennett GA (2001) Evidence that hypophagia induced by d-fenfluramine and d-norfenfluramine in the rat is mediated by 5-HT2C receptors. Neuropharmacology 41:200–209
Vickers SP, Easton N, Webster LJ et al (2003) Oral administration of the 5-HT2C receptor agonist, mCPP, reduces body weight gain in rats over 28 days as a result of maintained hypophagia. Psychopharmacology 167:274–280
Walsh AE, Smith KA, Oldman AD (1994) M-Chlorophenylpiperazine decreases food intake in a test meal. Psychopharmacology 116:120–122
Ward AS, Comer SD, Haney M et al (1999) Fluoxetine-maintained obese humans: effect on food intake and body weight. Physiol Behav 66:815–821
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Halford, J.C.G., Harrold, J.A. (2012). 5-HT2C Receptor Agonists and the Control of Appetite. In: Joost, HG. (eds) Appetite Control. Handbook of Experimental Pharmacology, vol 209. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-24716-3_16
Download citation
DOI: https://doi.org/10.1007/978-3-642-24716-3_16
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-24715-6
Online ISBN: 978-3-642-24716-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)