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.
In Vitro
JNJ-42226314 has IC 50 s 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
JNJ-42226314 (i.p.; 3 mg/kg and 30 mg/kg; 120 min) dose-dependently elevates hippocampal 2-AG in vivo . 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 . JNJ-42226314 (i.p.; 30 mg/kg) is antinociceptive in the rat complete Freund’s adjuvant (CFA) model of inflammatory pain . JNJ-42226314 has t 1/2 values of 11.4, 27.6, 27.2 min for MAGL in human, mouse and rat, respectively . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male C57Bl/6 mice weighing 20-30g and male Sprague-Dawley rats weighing 300-400 g Dosage: 3 mg/kg and 30 mg/kg Administration: i.p.; 120 min Result: Dose-dependently elevated hippocampal 2-AG in vivo.
