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Therapeutic Potential of Targeting the Endocannabinoids: Implications for the Treatment of Obesity, Metabolic Syndrome, Drug Abuse and Smoking Cessation

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Abstract:

Rimonabant (SR141716, Acomplia┬«) has been described as an antagonist/inverse agonist at the cannabinoid receptor type 1 (CB1). It has been widely used as a tool to evaluate the mechanisms by which cannabinoid agonists produce their pharmacological effects and to elucidate the respective physiological or pathophysiological roles of the CB1 receptor. It has become increasingly clear that rimonabant can exert its own intrinsic actions. These may be viewed as evidence of either the inverse agonist nature of rimonabant or of tonic activity of the endocannabinoid system. To date, data obtained from clinical trials (RIO North America, RIO Europe and RIO Lipid) indicate that rimonabant may have clinical benefits in relation to its anti-obesity properties and as a novel candidate for the treatment of metabolic and cardiovascular disorders associated with overweight and obesity. Other clinical trials, such as the STRATUS study, have also shown that rimonabant may be effective in smoking cessation, and that the drug has a reasonable safety profile. Recently, it has been shown that rimonabant prevents indomethacin-induced intestinal injury by decreasing the levels of pro-inflammatory cytokine tumour necrosis factor alpha (TNFα), thus indicating that CB1 receptor antagonists might exhibit potential antiinflammatory activity in acute and chronic diseases.

Keywords: Rimonabant/Acomplia/SR141716; addiction; appetite; cannabinoids; clinical trials; metabolism; obesity

Document Type: Research Article

DOI: https://doi.org/10.2174/092986706778201512

Affiliations: University of Liverpool,Eleanor Rathbone Building, Bedford Street South, Liverpool L69 7ZA, UK.

Publication date: 2006-09-01

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