The novel cannabinoid CB1 antagonist AM6545 suppresses food intake and food-reinforced behavior

Drugs that interfere with cannabinoid CB1 transmission suppress food-motivated behaviors, and may be useful clinically as appetite suppressants. However, there may also be undesirable side effects (e.g., nausea, malaise, anxiety, and depression) that are produced by the current generation of CB1 inverse agonists such as rimonabant and taranabant. For that reason, it is important to continue research on novel cannabinoid antagonists. The present studies examined the effects of the novel compound AM6545, which is a neutral antagonist of CB1 receptors that is thought to have relatively poor penetrability into the central nervous system. Intraperitoneal administration of AM6545 significantly reduced food-reinforced operant responding at doses of 4.0, 8.0 and 16.0 mg/kg. AM6545 also produced a strong suppression of the intake of high-carbohydrate and high-fat diets in the same dose range, but only produced a mild suppression of lab chow intake at the highest dose (16.0 mg/kg). Although AM6545 did not affect food handling, it did reduce time spent feeding and feeding rate. Taken together, these results suggest that AM6545 is a compound that warrants further study as a potential appetite suppressant drug.