New central targets for the treatment of obesity
Article first published online: 22 SEP 2009
© 2009 AMRI. Journal compilation © 2009 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 68, Issue 6, pages 852–860, December 2009
How to Cite
Sargent, B. J. and Moore, N. A. (2009), New central targets for the treatment of obesity. British Journal of Clinical Pharmacology, 68: 852–860. doi: 10.1111/j.1365-2125.2009.03550.x
- Issue published online: 27 NOV 2009
- Article first published online: 22 SEP 2009
- Received 13 March 2009 Accepted15 September 2009
- 1Center for Disease Control and Prevention. Available at http://www.cdc.gov/nccdphp/dnpa/obesity/trend/maps/ (last accessed 14 October 2009).
- 2Cardiovascular consequences of obesity. Drug Discov Today Ther Strat 2008; 5: 45–51., .
- 3Cardiovascular consequences of obesity and targets for treatment. Drug Discov Today Ther Strat 2008; 5: 53–61., .
- 4Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med 1999; 341: 1097–105., , , , .
- 5National medical spending attributable to overweight and obesity: how much, and who's paying? Health Affairs 2003; W3: 219–26., , .
- 6The consequences of childhood overweight and obesity. Future Child 2006; 16: 47–67..
- 7The obesity epidemic: pharmacological challenges. Mol Interv 2008; 8: 82–98., , , , , , .
- 8Overconsumption and obesity: peptides and susceptibility to weight gain. Regul Pept 2008; 149: 32–8., , , , , , , .
- 9Central nervous system control of food intake. Nature 2000; 404: 661–71., , , , .
- 10Central control of body weight and appetite. J Clin Endocrinol Metab 2008; 93: S37–50., .
- 11Brain circuits regulating energy homeostasis. Regul Pept 2008; 149: 3–10., .
- 12Gut hormones and appetite control. Oral Dis 2009; 15: 18–26., , .
- 13Obesity in neurobiology. Prog Neurobiol 2008; 84: 85–103., , .
- 14Neuroendocrine control of food intake. Nutr Metab Cardiovasc Dis 2008; 18: 158–68., , .
- 15Targeting melanocortin receptors: an approach to treat weight disorders and sexual dysfunction. Nat Rev Drug Discov 2008; 7: 307–23., .
- 16Sleep and metabolism: shared circuits, new connections. Trends Endocrinol Metab 2008; 19: 362–70., .
- 17Anti-obesity drugs and neural circuits of feeding. Trends Pharmacol Sci 2008; 29: 208–17., , .
- 18Leptin modulation of peripheral controls of meal size. Physiol Behav 2006; 89: 511–6., , .
- 19The hormonal control of food intake. Cell 2007; 129: 251–62., , .
- 20Novel functions of orexigenic hypothalamic peptides: from genes to behavior. Nutrition 2008; 24: 843–7., , , , .
- 21Pharmacological treatment of the overweight patient. Pharmacol Rev 2007; 59: 151–84., .
- 22Anti-obesity drugs: a critical review of current therapies and future opportunities. Pharmacol Ther 2001; 89: 81–121., , .
- 23Monoamine receptors in the regulation of feeding behaviour and energy balance. CNS Neurol Disord Drug Targets 2006; 5: 293–312., .
- 24Inhibition of dopamine and norepinephrine reuptake produces additive effects on energy balance in lean and obese mice. Neuropsychopharmacology 2007; 32: 822–34., .
- 25Enantioselective behavioral effects of sibutramine metabolites. Eur J Pharmacol 2000; 397: 93–102., , , , .
- 26Long term pharmacotherapy for obesity and overweight: updated meta-analysis. BMJ 2007; 335: 1194–9., , , , .
- 27http://www.fiercepharma.com/special-reports/can-obesity-treatment-be-cost-effective (last accessed 15 October 2009).. Available at
- 28Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet 2008; 372: 1859–60., , , , , .
- 29Company information. Available at http://www.medicalnewstoday.com/articles/83621.php (last accessed 15 October 2009).
- 305-HT2CRs expressed by pro-opiomelanocortin neurons regulate energy homeostasis. Neuron 2008; 60: 582–9., , , , , , , , , , .
- 31Serotonin 5-hydroxytryptamine2c receptor signaling in hypothalamic proopiomelanocortin neurons: role in energy homeostasis in females. Mol Pharmacol 2007; 72: 885–96., , , , , , .
- 32Serotonin reciprocally regulates melanocortin neurons to modulate food intake. Neuron 2006; 51: 239–49., , , , , , , , , , , , , , , , , , , , , , .
- 33Serotonin 2C receptor agonists improve type 2 diabetes via melanocortin-4 receptor signaling pathways. Cell Metab 2007; 6: 398–405., , , , , , , , , , , , , .
- 34Company information. Available at http://www.arenapharm.com (last accessed 15 October 2009).
- 35Selective 5-HT6 receptor ligands: progress in the development of a novel pharmacological approach to the treatment of obesity and related metabolic disorders. Pharmacol Ther 2008; 117: 207–31., , , , .
- 36A role for 5-HT6 receptors in retention of spatial learning in the Morris water maze. Neuropharmacology 2001; 41: 210–9., , , , .
- 37Chronic 5-HT6 receptor modulation by E-6837 induces hypophagia and sustained weight loss in diet-induced obese rats. Br J Pharmacol 2006; 148: 973–83., , , , , , , , , .
- 38A critical review of the cannabinoid receptor as a drug target for obesity management.Obes Rev 2008; 10: 58–67., , , , .
- 39CB1 receptor antagonism: biological basis for metabolic effects. Drug Discov Today 2008; 13: 1026–41..
- 40Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice. Am J Physiol Regul Integr Comp Physiol 2003; 284: R345–53., , , , , , .
- 41Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. J Am Med Assoc 2006; 295: 761–75., , , , .
- 42Obesity: what next after the CB1 antagonists' failure? Scrip 2008; 7 November 2008, 44–7..
- 43Company information. Available at http://www.orexigen.com (last accessed 15 October 2009).
- 44Company information. Available at http://www.vivus.com (last accessed 15 October 2009).
- 45A pair-feeding study reveals that a Y5 antagonist causes weight loss in diet-induced obese mice by modulating food intake and energy expenditure. Mol Pharmacol 2007; 71: 602–8., , , , , , , , , , , , , , .
- 46Neuropeptide Y Y5 receptor antagonists as anti-obesity drugs. Curr Opin Investig Drugs 2003; 4: 1198–204., .
- 47Neuropeptide Y5 receptor antagonism does not induce clinically meaningful weight loss in overweight and obese adults. Cell Metab 2006; 4: 275–82., , , , , , , , , , , , , , , , , , , , , , .
- 48Company information. Available at http://www.shionogiusa.com/media.html (last accessed 15 October 2009).
- 49Brain effects of melanocortins. Pharmacological Res 2008; 59: 13–47., , .
- 50The central melanocortin system directly controls peripheral lipid metabolism. J Clin Invest 2007; 117: 3475–88., , , , , , , , , , , , , , , , , , , , , , , , , .
- 51Anti-obesity effects of small molecule melanin-concentrating hormone receptor1 (MCHR1) antagonists. Life Sci 2007; 81: 423–40..
- 52MCH-R1 antagonists: what is keeping most research programs away from the clinic? Drug Discov Today 2007; 12: 972–9., .
- 53Melanin concentrating hormone-1 receptor antagonism decreases feeding by reducing meal size. Eur J Pharmacol 2004; 497: 41–7., , , , .
- 54Chronic MCH-1 receptor modulation alters appetite, body weight and adiposity in rats. Eur J Pharmacol 2003; 475: 37–47., , , , , , , , , , , , , .
- 55Comparative pharmacology of AMR-MCH-1 and AMR-MCH-2, MCH1 receptor antagonists for the treatment of obesity. Proceedings of the British Pharmacological Society (2008) Available at http://www.pA2online.org/abstracts/Vol6Issue4abst114P.pdf (last accessed 15 October 2009)., , , , , , , , , , , , , , , , .
- 56Company information. Available at http://www.neurogen.com/index.php?option=com_content&view=article&id=63&Itemid=78&p=irol-news (last accessed 15 October 2009).