Otenabant

Otenabant is a potent and selective cannabinoid receptor CB1 antagonist with K_i of 0.7 nM, exhibits 10,000-fold greater selectivity against human CB2 receptor. IC50 & Target: Ki: 0.7 nM (CB1) In Vitro: Otenabant HCl has low affinity with K_i of 7.6 μM for human CB2 receptors^[1]. Otenabant HCl inhibits CB1 receptor with moderate unbound microsomal clearance, low hERG affinity, and adequate CNS penetration^[2]. In Vivo: Otenabant acutely stimulates energy expenditure in rats and decreases the respiratory quotient indicating a metabolic switch to increased fat oxidation. Otenabant (10 mg/kg, p.o.) promotes a 9%, vehicle adjusted weight loss in a 10 day weight loss study in diet-induced obese mice^[1]. Otenabant HCl reverses four cannabinoid agonistmediated behaviors (locomotor activity, hypothermia, analgesia, and catalepsy) following administration of the synthetic CB1 receptor agonist CP-55940. Otenabant HCl exhibits dose-dependent anorectic activity in a model of acute food intake in rodents and increased energy expenditure and fat oxidation^[2].