O-Arachidonoyl Ethanolamine (hydrochloride) (Synonyms: OAEA, Arachidonic Acid(2aminoethyl)ester, Virodhamine)

Arachidonoyl ethanolamide (AEA) was the first endogenous cannabinoid to be isolated and characterized as an agonist acting on the same receptors (CB1 and CB2) as tetrahydrocannabinols (THC).1,2 Since that time, a number of related endocannabinoids have been isolated, most notably 2-arachidonoyl glycerol (2-AG).3 O-Arachidonoyl ethanolamine hydrochloride (O-AEA) is a recently isolated constituent of human and rat brain wherein the ethanolamine moiety is attached "backwards", as an ester instead of an amide, as in AEA.1,2,4 O-AEA has mixed agonist/antagonist activity at the CB1 receptor and does not appear to be the native endogenous cannabinoid agonist at this receptor. This is in keeping with other observations that 2-AG is the primary endogenous CB1 receptor ligand.5

References
1. Devane, W.A., Hanus, L., Breuer, A., et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258(5090), 1946-1949 (1992).
2. Felder, C.C., Briley, E.M., Axelrod, J., et al. Anandamide, an endogenous cannabimimetic eicosanoid, binds to the cloned human cannabinoid receptor and stimulates receptor-mediated signal transduction. Proc. Natl. Acad. Sci. U.S.A. 90(16), 7656-7660 (1993).
3. Sugiura, T., Kodaka, T., Kondo, S., et al. Is the cannabinoid CB1 receptor a 2-arachidonoylglycerol receptor• Structural requirements for triggering a Ca2+ transient in NG108-15 cells. J. Biochem. 122(4), 890-895 (1997).
4. Porter, A.C., Sauer, J.M., Knierman, M.D., et al. Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor. Journal of Pharmacology and Experimental Therapeutics 301(3), 1020-1024 (2002).
5. Sugiura, T., Kodaka, T., Nakane, S., et al. Evidence that the cannabinoid CB1 receptor is a 2-arachidonoylglycerol receptor. Structure-activity relationship of 2-arachidonoylglycerol, ether-linked analogues, and related compounds. J. Biol. Chem. 274(5), 2794-2801 (1999).