Concerns over the development of conditions such as primary pulmonary hypertension and valvular heart disease in patients taking serotonin releasing agents such as dexfenfluramine and fenfluramine led to searches for the agents that worked via serotonin but did not produce the same cardiovascular side effects. Sibutramine is a serotonin and noradrenaline reuptake inhibitor, pharmacologically distinct from these other drugs which are considered serotonin releasing agents, which was originally developed as an antidepressant . Early clinical studies showed sibutramine to be largely devoid of antidepressant properties, but resulted in weight loss . This therefore led to the development of sibutramine as an anti-obesity agent. Sibutramine has now been shown to be effective at producing weight loss in simple obesity and obesity associated with a range of co-morbidities including hypertension, dyslipidaemia and type 2 diabetes, and this chapter will describe its preclinical and clinical pharmacology, efficacy in clinical trials and describe the progress of long-term outcome trials with sibutramine, such as the Sibutramine Cardiovascular OUtcomes Trial (SCOUT study).
KeywordsPrimary Pulmonary Hypertension Weight Management Programme Produce Weight Loss Monoamine Reuptake Inhibitor Antiobesity Agent
Unable to display preview. Download preview PDF.
- 7.Jackson HC, Hutchins LJ, Mazurkiewicz SE, Heal DJ, Buckett WR (1996) Comparison of the effects of sibutramine and other monoamine reuptake inhibitors on food intake in the rat. Brit J Pharmacol 117: 323Google Scholar
- 8.Halford JCG, Heal DJ, Blundell JE (1995) Effects in the rat of sibutramine on food-intake and the behavioral satiety sequence. Brit J Pharmacol 114: p387Google Scholar
- 10.Rolls BJ, Shide DJ, Thorwart ML, Ulbrecht JS (1998) Sibutramine reduces food intake in nondieting women with obesity. Obesity Res 6: 1–11Google Scholar
- 16.Connoley IP, Frost I, Heal DJ, Stock MJ (1996) Role of beta-adrenoceptors in mediating the thermogenic effects of sibutramine. Brit J Pharmacol 117: p170Google Scholar
- 20.Finer N, Caterson I, Coutinho W, Van Gaal L, Maggioni A, Sharma A, Torp-Pedersen C, James WPT (2007) Clinically relevant weight loss achieved in high-risk patients during 6-week sibutramine treatment — an analysis from the sibutramine cardiovascular outcomes (SCOUT) trial. Int J Obesity 31: S29Google Scholar
- 21.Bray GA, Ryan DH, Gordon D, Heidingsfelder S, Cerise F, Wilson K (1996) Double-blind randomized placebo-controlled trial of sibutramine. Obesity Res 4: 263–270Google Scholar
- 23.Bray GA, Ryan DH, Gordon D, Heidingsfelder S, Cerise F, Wilson K (1996) Double-blind randomized placebo-controlled trial of sibutramine. Obesity Res 4: 263–270Google Scholar
- 26.Rissanen A, Taskinen MR (2000) Weight loss on sibutramine treatment for 12 months improves lipid profile in obese type 2 diabetic patients. Diabetologia 43: 657Google Scholar
- 31.Jordan J, Scholze J, Matiba B, Wirth A, Hauner H, Sharma AM (2005) Influence of Sibutramine on blood pressure: evidence from placebo-controlled trials. Int J Obesity 29(5): 509–516Google Scholar
- 35.Torp-Pedersen C, Caterson I, Coutinho W, Finer N, Van Gaal L, Maggioni A, Sharma A, Brisco W, Deaton R, Shepherd G et al. (2007) Cardiovascular responses to weight management and sibutramine in high risk subjects: an analysis from the SCOUT trial. Eur Heart J doi:10.1093/eurheartj/ehm217Google Scholar