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Arachidonoyl ethanolamide (AEA) was the first endogenous cannabinoid (CB) to be isolated and characterized as an agonist acting on the same receptors (CB1 and CB2) as Δ9-THC.1,2 Since that time, a number of related endocannabinoids have been isolated, most notably 2-arachidonoyl glycerol (2-AG).2 The phosphate ester of AEA, AEA-P, has been tested as a water soluble prodrug version of AEA in the treatment of C6 glioma cells in vivo. Here it acts with essentially the same potency as AEA.3 However, when tested for inhibition of AEA binding to isolated rat brain CB1 receptors, AEA-P is about 5-fold less potent as an agonist with a Ki of about 200 nM.4 The phosphate esters of AEA and its analogs are also structural variants of lysophosphatidic acid (LPA). However, the effects of AEA-P on the various LPA receptors have not been tested.
1
Devane, W.A., Hanus, L., Breuer, A., et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science2581946-1949(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 USA907656-7660(1993).
3
Fowler, C.J., Jonsson, K., Andersson, A., et al. Inhibition of C6 glioma cell proliferation by anandamide, 1-arachidonoylglycerol, and by a water soluble phosphate ester of anandamide: Variability in response and involement of arachidonic acid. Biochem Pharmacol66757-767(2003).
4
Sheskin, T., Hanus, L., Slager, J., et al. Structural requirements for binding of anandamide-type compounds to the brain cannabinoid receptor. J Med Chem40659-667(1997).
Devane, W.A., Hanus, L., Breuer, A., et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science2581946-1949(1992).
Sheskin, T., Hanus, L., Slager, J., et al. Structural requirements for binding of anandamide-type compounds to the brain cannabinoid receptor. J Med Chem40659-667(1997).
Fowler, C.J., Jonsson, K., Andersson, A., et al. Inhibition of C6 glioma cell proliferation by anandamide, 1-arachidonoylglycerol, and by a water soluble phosphate ester of anandamide: Variability in response and involement of arachidonic acid. Biochem Pharmacol66757-767(2003).
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 USA907656-7660(1993).