R-1 Methanandamide Phosphate

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 ?9-THC.{1134,2713} Since that time, a number of related endocannabinoids have been isolated, most notably 2-arachidonoyl glycerol (2-AG).{2713} The phosphate ester of R-1 methanandamide, R-1MAP, has been tested as a water soluble prodrug analog of AEA.{11520} The activity of R-1MAP was essentially equivalent to that of AEA in the growth inhibition of C6 glioma cells. However, when tested for inhibition of AEA binding to isolated rat brain CB1 receptors, arachidonoyl ethanolamide phosphate (AEA-P) is about 5-fold less potent as an agonist with a Ki of about 200 nM.{9580} The phosphate esters of AEA and its analogs are also structural variants of lysophosphatidic acid (LPA). However, the effects of R-1MAP on the various LPA receptors have not been tested.