JZL195

Description: JZL195 is a potent, selective and efficacious dual FAAH/MAGL (fatty acid amide hydrolase/monoacylglycerol lipase) inhibitor with IC50 of 13 nM and 19 nM for mouse brain FAAH and MAGL respectively. JZL195 exhibits broad activity in the tetrad test for CB1 agonism, causing analgesia, hypomotilty, and catalepsy. Comparison of JZL195 to specific FAAH and MAGL inhibitors identified behavioral processes that were regulated by a single endocannabinoid pathway (e.g., hypomotility by the 2-AG/MAGL pathway) and, interestingly, those where disruption of both FAAH and MAGL produced additive effects that were reversed by a CB1 antagonist. In addition, JZL195 reduces inflammation induced allodynia at doses below those which produce side-effects, and displays greater efficacy that FAAH or MAGL inhibitors. Thus, dual FAAH/MAGL inhibition has the potential to alleviate inflammatory pain with reduced cannabinoid-like side-effects.

References: Proc Natl Acad Sci U S A. 2009 Dec 1; 106(48):20270-5; Neuropharmacology. 2014 Jun; 81:224-30.