A neutral CB1 receptor antagonist reduces weight gain in rat

• DOI: 10.1152/ajpregu.00663.2007
• Publication Date: 2007-10-24T23:00:42Z
• Authors: Adam P. Chambers; V. Kiran Vemuri; Yan Peng; JodiAnne T. Wood; Teresa Olszewska; Quentin J. Pittman; Alexandros Makriy...; Keith A. Sharkey
• Keywords: AM251; Inverse agonist; Anorectic; Cannabinoid receptor antagonist; Rimonabant

Cannabinoid (CB)1 receptor inverse agonists inhibit food intake in animals and humans but also potentiate emesis. It is not clear whether these effects result from agonist properties or the blockade of endogenous cannabinoid signaling. Here, we examine effect a neutral CB1 antagonist, AM4113, on intake, weight gain, Neutral antagonist binding were confirmed HEK-293 cells transfected with human CB2 receptors. AM4113 had no forskolin-stimulated cAMP production at concentrations up to 630 nM. The Ki value (0.80 +/- 0.44 nM) competitive assays CB1/2 [3H]CP55,940 was 100-fold more selective for over We determined that antagonized receptors brain by blocking hypothermia induced CP55,940. (0-20 mg/kg) significantly reduced gain rat. Compared AM251, higher doses needed produce similar body weight. Unlike AM251 (5 mg/kg), highly anorectic dose (10 did vomiting emetic morphine-6-glucoronide. show centrally active shares appetite suppressant loss agonists. If compounds display humans, they could be developed into new class antiobesity agents.