Description
(±)-
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 CB
1 receptor (K
i = 5.7 nM in rat brain). It also confers additional selectivity, in that binding to CB
2 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 Δ
9-
THC in animal self-
administration tests, whereas AEA and 2-
fluoro AEA cannot.
References
[1] Cozzolino R, et al. A metabolically stable analogue of anandamide, Met-F-AEA, inhibits human thyroid carcinoma cell lines by activation of apoptosis. Invest New Drugs. 2010 Apr;28(2):115-23. DOI:
10.1007/s10637-009-9221-0
