Rimonabant (SR141716)

463, 79

Male mice and male rats

Rimonabant is now under the Phase III clinical trial for the effects on weight gain and body composition in adults with Prader Willi Syndrome.

20 ml/kg (mice) and 5 ml/kg (rats)

13.6 nM, 13.6 nM, 13.6 nM, 13.6 nM, 13.6 nM, 13.6 nM

Rimonabant is administered intraperitoneally or orally potently and dose-dependently antagonize classical pharmacological and behavioural effectos of cannabinoid receptor agonists. [3] In the mouse model of azoxymethane-induced colon carcinogenesis, Rimonabant significantly decreased aberrant crypt foci (ACF) formation, which precedes colorectal cancer. [4] Rimonabant (10 mg/kg by gavage) is fed for 2 weeks to 3-month-old male obese Zucker rats as an impaired glucose tolerance model and for 10 weeks to 6-month-old male obese Zucker rats as a model of the metabolic syndrome. RANTES (Regulated upon Activation, Normal T cell Expressed, and Secreted) and MCP-1 (monocyte chemotactic protein-1) serum levels are increased in obese vs lean Zucker rats and significantly reduced by long-term treatment with Rimonabant, which slowes weight gain in rats with the metabolic syndrome. Neutrophils and monocytes are significantly increased in young and old obese vs lean Zucker rats and lowered by Rimonabant. Platelet-bound fibrinogen is significantly enhanced in obese vs lean Zucker rats of both age, and is reduced by Rimonabant. Platelets from obese rats are more sensitive to thrombin-induced aggregation and adhesion to fibrinogen, which are both attenuated by Rimonabant therapy. [5]

Radioligand Binding Assay, Human CB1 and CB2 stably transfect HEK 293 cells and cell membrane is purified. 0.2–8 ug of the purified membrane is incubated with 0.75 nM [3H] CP55, 940 and Rimonabant in the incubation buffer (50 mM Tris-HCl, 5 mM MgCl2, 1 mM EDTA, 0.3%BSA, pH 7.4). The non-specific binding is defined in the presence of 1 uM of CP55, 940. The reactions are incubated for one and a half hours at 30 C in Multiscreen. The reactions are terminated by manifold filtration and washed four times with ice-cold wash buffer (50mM Tris, pH 7.4, 0.25% BSA).The radioactivity bound to the filters is measured by Topcount. The IC50 is determined as the concentration of Rimonabant required to inhibit 50% of the binding of [3H] CP55, 940 and calculated by non-linear regression.

DMSO 25 mg/mL, Water <1 mg/mL, Ethanol 2 mg/mL

5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide