Endocannabinoids such as 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide (AEA) are biologically active lipids that are involved in a number of synaptic processes including activation of cannabinoid receptors. Monoacylglycerol lipase (MAGL) is a serine hydrolase responsible for the hydrolysis of 2-AG to arachidonic acid and glycerol, thus terminating its biological function. JZL 184 is a potent and selective inhibitor of MAGL that displays IC50 values of 8 nM and 4 µM for inhibition of MAGL and fatty acid amide hydrolase in murine brain membranes, respectively.1 When administered to mice at 16 mg/kg, intraperitoneally, JZL 184 reduces MAGL activity by 85%, elevates brain 2-AG levels by 8-fold, and elicits analgesic activity in a variety of pain assays that qualitatively mimics direct central cannabinoid (CB1) agonists.1
1
Long, J.Z., Li, W., Booker, L., et al. Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects. Nat Chem Biol5(1)37-44(2009).