Obesity is now the most common nutritional disorder in western industrialized countries. Defined as a body mass index of greater than 30, it arises from the accumulation of excess fat in the body from over consumption of fatty foods. Prevalence of obesity in the US and Europe has reached epidemic levels.
Data from the World Health Organization’s MONICA project show that in some parts of Europe over 70% of men aged 55-64 years are clinically obese or overweight (BMI >25) and almost 70% of women in this age group. One in five of all Americans is obese and one in three overweight. Furthermore, increasing rates of childhood obesity are likely to exacerbate the trend towards increasing obesity in adulthood.
Aware of these facts scientists from Sanofi-Aventis developed a substance to inhibit appetite. Sanofi-Aventis’ approach in development of Rimonabant came from the knowledge that cannabis smokers often experience extreme hunger sensations, 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 is an anorectic anti-obesity drug. Its main avenue of effect is reduction in appetite. Rimonabant is the first selective CB1 receptor blocker approved for human consumption. In Europe, it is indicated for use in conjunction with diet and exercise for patients with a body mass index greater than 30 kg/m2, or patients with a BMI greater than 27 kg/m2 with associated risk factors, such as type 2 diabetes or dyslipidaemia. In the UK, it has been available since the end of July 2006.
On 21 June 2006, the European Commission approved the sale of Rimonabant in the then 25-member European Union. Sanofi, Rimonabant manufacturer, soon after announced that the first country in which Acomplia, brand name under which Rimonabant is sold, will be sold is the United Kingdom. Sales began in July 2006. Sanofi also announced that it projects that the drug will be sold shortly thereafter in Denmark, Ireland, Germany, Finland and Norway.
Rimonabant works by blocking endogenous cannabinoid binding to neuronal CB1 receptors. Activation of these receptors by endoegenous cannabinoids, such as anadamide, increases appetite. It is the most advanced endocannabinoid receptor antagonist in clinical development and offers a novel therapeutic approach to appetite control and weight reduction. The drug also has potential as a treatment for smoking cessation because the endocannabinoid system is involved in the body’s response to tobacco dependence.
Efficacy and safety in long-term use is important feature of any antiobesity drug. Some potential antiobesity medications have proved effective in the first six months of treatment only to lose effectiveness as subjects develop resistance to treatment. Data from the RIO trials suggest Rimonabant is effective for maintaining weight loss for periods of at least two years.