JW 618

Endocannabinoids such as 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide 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. JW 618 is an inhibitor of MAGL that displays IC50 values of 123, 385, and 6.9 nM for inhibition of MAGL in mouse, rat, and human brain membranes, respectively. JW 618 is selective for MAGL, requiring much higher concentrations to effectively inhibit fatty acid amide hydrolase activity (IC50s all > 50 µM for mouse, rat, and human brain membranes).