Obesity rimonabant

Our current understanding of the potential therapeutic applications of CBi antagonists owes a great deal to the discovery of rimonabant (382). Indeed, clinical data demonstrating the efficacy of (382) in the treatment of obesity and nicotine addiction has provided a substantial driving force for the expanding research effort into this approach. 

Specific adverse effects of rimonabant have not yet been released to the public, although the company that makes the drug reports that their incidence is low. Pending the completion of more safety and efficacy studies, rimonabant is expected to be available in the United States in the next couple of years. This drug may prove to be especially ideal for obese individuals who smoke, since it should help with both problems. 

Pi-Sunyer FX, Aronne LJ, Heshmati HM, Devin J, Rosenstock J, RIO-North America Study Group (2006) Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabohc risk factors in overweight or obese patients RIO-North America a randomized controlled trial. JAMA 295 761-775... 

Rimonabant is an inverse agonist for the cannabi-noid receptor CBl. In 2006 rimonabant was approved in the European Union as an anti-obesity drug. The use of rimonabant after one year produces a modest weight loss of approximately 5%. However there are serious concerns over suicidality, depression and other related side effects associated with use of the drug. In Europe, rimonabant is now contraindicated for patients with severe depression. 

Curioni C, Andre C. Rimonabant for overweight or obesity. Cochrane Database Syst Rev 2006. 

Rimonabant CBi receptor agonist Decreases neurotransmitter release at GABAergic and glutamatergic synapses Approved in USA and Europe to treat obesity Smoking cessation is an off-label indication Major depression, including increased risk of suicide... 

Scheen Al, Finer N, Hollander P, Jensen M, Van Gaal L, Group ftR-DS. Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes a randomised controlled study. Lancet 2006 368 1660-1672. 

Rimonabant may also alter reward pathways that promote addictive behaviors such as overeating. This drug has been shown to attenuate the rewarding effects of alcohol in a strain of alcohol-preferring rat s (161) and may similarly diminish the pleasurable effects of food and overeating that can often play important roles in the etiology of obesity. 

Bensaid, M. Rimonabant reduces obesity-associated hepatic steatosis and features of metabolic syndrome in obese Zucker fa/fa rats. 

The appetite-stimulating effects of marijuana have been known for centuries and constitute one of the established medicinal uses of cannabis preparations. Today THC (dronabinol/Marinol) is clinically used for the treatment of cachexia-anorexia in human immunodeficiency virus (HIV) and palliative care patients. There have also been very promising advances in the development of a cannabinoid receptor antagonist (SR141716A, now named Rimonabant or Acomplia) for the treatment of obesity. 

The endocannabinoid system is implicated in the physiological control of food intake and energy balance, not only after food deprivation but also in animal models of genetic obesity in which it appears to become overactive at the level of both the hypothalamus and adipocytes (Di Marzo et al. 2001c Bensaid et al. 2003). This possibly explains why, following treatment of mice and rats with rimonabant, a transient inhibition of food intake and a more persistent reduction of fat mass are observed (Ravinet-Trillou et al. 2003), and why CBi knockout mice show a reduced susceptibility to obesity in response to a fat diet (Ravinet-Trillou et al. 2004). 

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