Rimonabant for the treatment of obesity

Obesity is a growing public health problem that is already reaching epidemic proportions and is increasingly encompassing young children and adolescents. Despite the increasing prevalence and the health risks associated with obesity, the pharmacotherapeutic options for treating obesity are limited. The endogenous cannabinoid or endocan-nabinoid system (ECS) was discovered in the early 1990s in relation to work on the action of components of marijuana. Central activation of the ECS promotes food ingestion. The endogenous cannabinoids exert their pharmacologic action through interaction with the specific receptors, CB(1) and CB(2). CB(1) receptors are located predominantly in the brain and peripherally in adipose tissue, liver, skeletal muscle and the gastrointestinal tract. In July 2006, European regulatory authorities approved the use of rimonabant, SR141716, a selective CB1 receptor antagonist, in obese patients (BMI > or =30kg/m(2), or >27kg/m(2) with complications). However, in June 2007, despite extensive clinical trial data, the FDA's Endocrine and Metabolic Drugs Advisory Committee (EMDAC) concluded that the safety of rimonabant had not been adequately demonstrated by the manufacturer Sanofi-Aventis; the full application was subsequently withdrawn. This review article provides evidence and outlines some patents for the use of rimonabant and potential safety concerns which still prevent its use in the single largest market for drugs of its kind.