Not surprisingly, the growing prevalence of obesity has stimulated the search for drugs to treat this condition. Various therapeutic strategies have been explored, including:

• Serotonin and noradrenaline reuptake inhibitors (anorectic agents)
• Lipase inhibitors
• ß 3-adrenoreceptor agonists
• Leptin agonists
• Melanocortin-3 agonists

Sanofi-Aventis’ approach is completely different to the above. It developed from the knowledge that cannabis smokers often experience extreme hunger pangs, which cannabis smokers refer to as “the munchies”. Sanofi-Aventis worked on the premise that if cannabinoids stimulate appetite, blocking cannabinoid receptors in the brain might reduce appetite.

The central cannabinoid (CB1) receptors are believed to play a role in controlling food consumption and the phenomena of dependence / habituation. To develop suitable drugs against this target, the human cannabinoid receptor was first cloned and then expressed in cells.

Compounds with potential inhibitory activity against this receptor were then screened for inhibitory activity. Rimonabant emerged from this screening process as a potent CB1 receptor antagonist. Preclinical animal studies subsequently showed that it could reduce consumption of fats and sugars, which contribute to weight gain.