JNJ-42226314 is a competitive, highly selective and reversible non-covalent monoacylglycerol lipase (MAGL) inhibitor. JNJ-42226314 demonstrates dose-dependent enhancement of the major endocannabinoid 2-arachidonoylglycerol (2-AG) as well as efficacy in models of neuropathic and inflammatory pain[1].
JNJ-42226314 has IC50s of 1.13 nM, 1.88 nM, 0.67 nM, 0.97 nM for human Hela cells, human PBMC, mouse brain and rat brain, respectively[1].
JNJ-42226314 (i.p.; 3 mg/kg and 30 mg/kg; 120 min) dose-dependently elevates hippocampal 2-AG in vivo[1]. JNJ-42226314 (i.p.; 30 mg/kg)significantly increases total wake time for up to 8 hours afterward, whereas total wake time was only elevated for 2 hr following a 3 mg/kg dose[1]. JNJ-42226314 (i.p.; 30 mg/kg) is antinociceptive in the rat complete Freund's adjuvant (CFA) model of inflammatory pain[1]. JNJ-42226314 has t1/2 values of 11.4, 27.6, 27.2 min for MAGL in human, mouse and rat, respectively[1]. Animal Model: Male C57Bl/6 mice weighing 20-30g and male Sprague-Dawley rats weighing 300-400 g[1]
[1]. Wyatt RM, et al.Pharmacologic characterization of JNJ-42226314, [1-(4-fluorophenyl)indol-5-yl]-[3-[4-(thiazole-2-carbonyl)piperazin-1-yl]azetidin-1-yl]methanone, a reversible, selective and potent monoacylglycerol lipase inhibitor.J Pharmacol Exp Ther. 2019 Dec 9.