(±)-2-Methyl Arachidonoyl-2'-Fluoroethylamide

(±)-2-Methyl arachidonoyl-2'-fluoroethylamide (2-Methyl-2'-fluoro AEA) is an analog of anandamide (AEA) in which the alcohol of the ethanolamide group has been removed and replaced with a fluorine atom. This substitution confers considerably increased binding affinity for the CB1 receptor (Ki = 5.7 nM in rat brain). It also confers additional selectivity, in that binding to CB2 is decreased relative to AEA. However, the in vivo activity of 2-fluoro AEA is enhanced much less than the binding affinity, because the analog remains a good substrate for FAAH and is rapidly hydrolyzed by this enzyme. 2-Methyl-2'-fluoro AEA is further modified by the addition of an α-methyl group at the C-2 position of arachidonic acid. This substitution confers enhanced metabolic stability. 2-Methyl-2'-fluoro AEA can fully substitute for δ9-THC in animal self-administration tests, whereas AEA and 2-fluoro AEA cannot.