JZL195

JZL195 is a potent dual inhibitor of Monoacylglycerol lipase (MAGL) (IC₅₀ = 2 nM) and fatty acid amide hydrolase (FAAH) (IC₅₀ = 4 nM), enzymes that degrade the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA), the endogenous ligands for the cannabinoid G-protein coupled receptors CB1 and CB2. It poorly inhibits neuropathy target esterase and ABHD6 and does not inhibit other brain serine hydrolases. JZL 195 displays time-dependent inhibition of FAAH and MAGL in vivo, consistent with a covalent mechanism of activation.