URB-597

A potent and selective FAAH inhibitor with IC50 of 4.6 nM; increases anandamide levels in the brain of rats and wild-type mice (0.3 mg/kg i.p.) ; improves cognitive impairment by inhibiting mTOR-dependent autophagy in a CCH model.Anxiety Preclinical (In Vivo) :URB-597 (KDS-4103) inhibits rat brain FAAH activity after intraperitoneal (i.p.) administration with a median inhibitory dose (ID50) of 0.15 mg/kg in wild-type mice (+/+) or FAAH-null mice (-/-) .KDS-4103 (0.1-0.3 mg/kg, i.p.) elicits significant, anxiolytic-like, antidepressant-like and analgesic effects, which are prevented by treatment with CB1 receptor antagonists in rats and mice.KDS-4103 is orally available in rats and cynomolgus monkeys.URB-597 inhibits FAAH in the brain rapidly (1 h), sustains at >90% through 12 h and >60% through 24 h after an oral dose of 10 mg/kg.