Endocannabinoids such as 2-arachidonoyl glycerol (2-AG; Item No. 62160) and arachidonoyl ethanolamide (AEA; Item No. 90050) are biologically active lipids that are involved in a number of synaptic processes including activation of cannabinoid (CB) receptors. Fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) mediate the hydrolysis of AEA and 2-AG, respectively. MAGL inhibitor 21 selectively binds to MAGL (K_i = 0.4 µM) and reversibly blocks the enzyme’s activity in mouse brain with an IC₅₀ value of 0.18 µM.¹ Comparatively, MAGL inhibitor 21 is reported to inhibit FAAH activity in mouse brain with an IC₅₀ value of 59 µM.² This compound does not bind CB₁ or CB₂ receptors and does not inhibit the related serine hydrolases ABHD6 and ABHD12 (K_is > 10 µM).¹ In a mouse model of multiple sclerosis, 5 mg/kg of MAGL inhibitor 21 has been used to ameliorate progression of the disease without producing detrimental CB₁-mediated effects.¹

≥98%