Rimonabant in the management of cardiovascular risk

Abstract

4 F U T U R E P R E S C R I B E R V O L 7 ( 2 )w w w . e s c r i b e r . c o m D R U G P R O F I L E r i m o n a b a n tRimonabant in the management of cardiovascular risk Figure 1. Obesity poses one of the greatest modern healthcare challenges.SPL glucose level greater than 5.5mmol/l. 5 It has been argued that unless there are effective population-level inter ventions to reduce obesity on a consistent and regular basis, the steady rise in life expectancy that has been a feature of the past century could come to an end. 6 For obese subjects, weight loss of between 5-10 per cent can significantly improve risk factors for obesity-related diseases and delay, or prevent, development of type 2 diabetes. 7 Achieving and maintaining weight loss through lifestyle changes alone is difficult for many overweight people and, while behavioural and cognitive treatments can work for some individuals, these approaches have not had broad success. Despite many efforts to find adjunctive treatments to support obese patients in achieving clinically meaningful weight loss, there have, until recently, been few successes in this therapeutic area. 3,7 The history of weight-loss medications includes the use and abuse of amphetamines and a host of drugs withdrawn due to safety concerns. 7 Many potential therapies designed to promote weight loss have been plagued with unwanted side-effects and poor safety profiles. The result is that there are now only two widely approved adjunctive therapies for obesity management -sibutramine (a centrally-acting noradrenaline and serotonin reuptake inhibitor) and orlistat (an inhibitor of gastric and intestinal lipase). THE CANNABINOID SYSTEM: A NEW THERAPEUTIC TARGET IN OBESITY CONTROLRecent research has identified the endocannabinoid system as playing a crucial role in the control of food intake and energy balance in humans. This has led to interest in pharmacological manipulation of this system to induce weight loss and improve the metabolism of carbohydrates and lipids in obese subjects. [8][9][10] The endocannabinoid system consists of G1/0-protein-coupled CB1 receptors (which are expressed in several areas of the brain, in the autonomic nervous system and in peripheral organs such as liver, muscle, the gastrointestinal tract and adipose tissue) 11 and a family of locally produced, short-lived endogenous agonists for these receptorsthe endocannabinoids. 9,10 In recent years, a growing body of evidence has shown that stimulation of central CB1 receptors in the hypothalamus by endocannabinoid moieties can provoke food intake, even in satiated animals, and it has also been demonstrated that CB1 stimulation in fat cells promotes lipogenesis and inhibits the production of adiponectin, a cytokine with antidiabetic and antiatherosclerotic properties. 9 Central CB1 receptors also appear to be expressed in the brain in 'reward circuits' of the mesolimbic system that are activated by psychostimulants such as nicotine and drugs associated with the phenomena of habituation and dependence. 12 RIMONABANT: DEVELO...