Arachidonoylethyleneglycol and its nitroester as new cannabimimetics: Oxidation by 15-lipoxygenase and hydrolysis by fatty acid amide hydrolase

Arachidonoylethyleneglycol (AEG) and 1-O-arachidonoyl-2-O-nitroethyleneglycol (ANEG) were synthesized. Both compounds were preliminarily tested in vivo in the tetrad of cannabimimetic tests and showed strong cannabimimetic properties. 15-Lipoxygenase converted AEG into single and double lipoxygenation products, whereas ANEG turned out to be a poor substrate for this enzyme. AEG was capable of hydrolysis by anandamide amidohydrolase in mouse neuroblastoma N18TG2 cells and of the inhibition of corresponding anandamide hydrolysis. It is suggested that AEG may be a new natural endocannabinoid.