565460-15-3

IC50: 28±4 μM (rat brain MGL)

Without URB602, the apparent Michaelis constant (K _m ) of MGL for 2-AG is 24±1.7 μM and the maximum velocity (V _max ) is 1814±51 nmol min per mg protein; with URB602, the K _m is 20±0.4 μM and the V _max is 541±20 nmol min per mg protein (n=4). When organotypic slice cultures of rat forebrain are incubated with URB602 (100 μM), both baseline and Ca ²⁺ -ionophore-stimulated 2-arachidonoylglycerol (2-AG) concentrations are increased. URB602 is an inhibitor of monoacylglycerol lipase (MGL), a serine hydrolase involved in the biological deactivation of the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG). URB602 weakly inhibits recombinant MGL (IC ₅₀ =223±63 μM) through a rapid and noncompetitive mechanism.

URB602 at doses of 20 and 40 mg/kg tends to reduce upper GI transit and slow colonic propulsion. When taken together as whole gut transit, URB602 dose dependently inhibits transit (P<0.05) compared with the vehicle control group. The inhibitory action of 40 mg/kg URB602 on whole gut transit is absent in these mice, indicating CB ₁ receptor involvement in the inhibitory action. URB602 decreases the AUC of pain behaviour during the early phase of the formalin test with an ED ₅₀ of 0.06±0.028 μg for JZL184 and 120±51.3 μg for URB602 in adult male Sprague-Dawley rats. Both MGL inhibitors also suppresses pain behaviour during the late phase of formalin pain, with an ED ₅₀ of 0.03±0.011 μg for JZL184 and 66±23.9 μg for URB602.