2-Arachidonyl glycerol ether (2-AG ether) has been isolated from porcine brain and its structure determined by mass spec analysis. 2-AG ether has also been synthesized as an analog of the endogenous cannabinoid (CB), 2-AG, for structure activity testing. 2-AG ether is a selective central cannabinoid (CB1) receptor agonist exhibiting Ki values of 21.2 nM and >3 μM at the CB1 and peripheral cannabinoid (CB2) receptors, respectively, and displays the typical tetrad of CB activities in mice. It is much more chemically stable than 2-AG, with an endogenous half-life of hours rather than minutes. However, it is at least 10-fold less potent than 2-AG in eliciting typical CB1-mediated responses. 2-AG ether elicits modest reductions in IOP in rabbits when administered at doses exceeding 50 μg per eye. 2-AG ether increases aqueous humor outflow via the CB1 receptor in the trabecular meshwork.
