Rimonabant

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Rimonabant
Systematic (IUPAC) name
5-(4-Chlorophenyl)-1-(2,4-dichloro-phenyl)- 4-methyl-N-(piperidin-1-yl)- 1H-pyrazole-3-carboxamide
Identifiers
CAS number	158681-13-1
ATC code	?
PubChem	104850
Chemical data
Formula	C₂₂H₂₁Cl₃N₄O
Mol. mass	463.79 g/mol
Pharmacokinetic data
Bioavailability	Undetermined
Protein binding	Nearly 100%
Metabolism	Hepatic, CYP3A4 involved
Half life	Variable: 6 to 9 days with normal BMI 16 days if BMI >30
Excretion	Fecal (86%) and renal (3%)
Therapeutic considerations
Licence data	EU
Pregnancy cat.	Not assigned. Use not recommended
Legal status	POM(UK)
Routes	Oral

Rimonabant (SR141716) is an anorectic anti-obesity drug. It is a CB1 cannabinoid receptor antagonist. Its main avenue of effect is reduction in appetite. Rimonabant is currently being sold in the United Kingdom by Sanofi-Aventis and in Denmark by Sanofi-Synthelabo under the trade name Acomplia. It is believed, although not confirmed, that if the drug is approved in the United States, it will be sold under the trade name Zimulti.

Rimonabant is the first selective CB1 receptor blocker to be approved for use anywhere in the world. 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 wih 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.

1 Approval
2 Side effects
3 Smoking cessation
4 External links

[edit] Approval

Despite the FDA issuing an approval letter in February 2006 for the obesity indication and a non-approval letter for smoking cessation, the drug did not enter the market in the United States in 2006. Sanofi-Aventis has disclosed that a complete response to the FDA's approvable letter was submitted on October 26, 2006. This triggers either a Class I (two-month) or Class II (six-month) review process. Neither the FDA nor Sanofi-Aventis has revealed the precise nature of the revised submission.

On 21 June 2006, the European Commission approved the sale of rimonabant in the then 25-member European Union. Sanofi announced that the first country in which Acomplia 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. It is expected in Belgium^[1] and Sweden in 2007. Ordinary obesity will, according to official medical recommendations, not be enough to acquire the prescription in Sweden; there are additional requirements concerning abnormal blood lipid levels.^[2]

The EU's approval was not a blanket approval, nor did it approve Acomplia for non-obesity related problems such as smoking cessation, although off-label use of the drug is still possible. The approval is in combination with diet and exercise for the treatment of obese patients (BMI greater than or equal to 30), or overweight patients (BMI greater than 27) with associated risk factors, such as type 2 diabetes or dyslipidaemia.

[edit] Side effects

Shortly after market introduction, press reports and independent studies suggest that side effects occur stronger and more commonly than shown by the manufacturer in his clinical studies. Reports of severe depression are frequent. This is deemed to result from the drug being active in the central nervous system, an area of human physiology so complex that drug effects are highly difficult to determine reliably. [1] The reported development of previously clinically silent multiple sclerosis in one patient taking Rimonabant suggests that any patients with an underlying neurological condition should not take Rimonabant, given the neuroprotective role of the cannabinoid system in many experimental paradigms of neurological disease.

[edit] Smoking cessation

Rimonabant may also be found to be effective in assisting some smokers to quit smoking. Sanofi-Aventis is currently conducting studies to determine the possible value of rimonabant in smoking-cessation therapy. The Studies with Rimonabant and Tobacco Use (STRATUS) Program involves more than 6,000 subjects. STRATUS is designed to explore two smoking-related therapies. First, to use rimonabant directly to aid in smoking cessation. Second, to help prevent weight gain in former smokers. Initial results apparently suggest that rimonabant is effective for both uses. However, the FDA has explicitly stated to Sanofi-Aventis that without additional studies rimonabant cannot be approved in the United States for smoking cessation therapy.

[edit] External links

Sanofi-Aventis – web site of the developer of rimonabant
Detailed clinical information for physicians
electronical Medicines Compendium - UK resource with Acomplia prescribing information
Acompliareport - Complete news and reviews related to rimonabant, updated daily
Chemistry in Context: Acomplia - Acomplia - Miracle Drug against Obesity