JZL195 functions as a dual inhibitor of FAAH and MAGL with IC50 of 13 nM and 19 nM respectively in brain of mouse.
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JZL195 is a selective and efficacious dual FAAH/MAGL inhibitor with IC50 values of 2nM and 4nM, respectively. It exhibited broad activity in the tetrad test for CB1 agonism, causing analgesia, hypomotilty, and catalepsy. Male C57BL/6 mice administered JZL195 at doses ranging in 3–20mg/kg, i.p., for 4h showed dose-dependent reductions in brain FAAH, MAGL, and ABHD6 activities as judged by gel-based ABPP that correlated with near-complete inhibition of both AEA and 2-AG hydrolysis[6]. JZL195 reduced inflammation induced allodynia, mechanical allodynia and thermal hyperalgesia, as well as produced catalepsy and sedation in a dose dependent manner. It displays greater efficacy than FAAH or MAGL specific inhibitors[7].
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