资料参考

IC 50 value: 0.7nM(Ki for binding)/0.2 nM (Ki for function) Otenabant (CP-945,598) is a recently discovered selective, high affinity, competitive CB1 receptor antagonist that inhibits both basal and cannabinoid agonist-mediated CB1 receptor signaling. Cannabinoid CB1 receptor antagonists exhibit pharmacologic properties favorable for the treatment of metabolic disease. in vitro, ex vivo, and in vivo data indicate that Otenabant (CP-945,598) is a novel CB(1) receptor competitive antagonist that may further our understanding of the endocannabinoid system[1]. in vitro : Otenabant (CP-945,598) exhibits sub-nanomolar potency at human CB1 receptors in both binding (Ki = 0.7 nM) and functional assays (Ki = 0.2 nM). The compound has low affinity (Ki = 7600 nM) for human CB2 receptors[1]. in vivo: Otenabant (CP-945,598) reverses four cannabinoid agonist-mediated CNS-driven responses (hypo-locomotion, hypothermia, analgesia, and catalepsy) to a synthetic cannabinoid receptor agonist. Otenabant (CP-945,598) exhibits dose and concentration-dependent anorectic activity in two models of acute food intake in rodents, fast-induced re-feeding and spontaneous, nocturnal feeding. Otenabant (CP-945,598) also acutely stimulates energy expenditure in rats and decreases the respiratory quotient indicating a metabolic switch to increased fat oxidation. CP-945,598 at 10 mg/kg promoted a 9%, vehicle adjusted weight loss in a 10 day weight loss study in diet-induced obese mice[1]. After oral administration of a single dose of [(14)C]CP-945,598. Total mean recoveries of the radioactive dose were 97.7, 97.8, and 99.3% from mice, rats, and dogs respectively[2]. Clinical trail: A phase 1 study of the roles of endocannabinoids in insulin secretion and action is recruiting.