2-Arachidonyl glycerol ether (2-AG ether) has been isolated from porcine brain and its structure determined by mass spec analysis.¹ 2-AG ether has also been synthesized as an analog of the endogenous cannabinoid (CB), 2-AG, for structure activity testing.² 2-AG ether is a selective central cannabinoid (CB₁) receptor agonist exhibiting K_i 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.¹ It is much more chemically stable than 2-AG, with an endogenous half-life of hours rather than minutes.³ However, it is at least 10-fold less potent than 2-AG in eliciting typical CB₁-mediated responses.² 2-AG ether elicits modest reductions in IOP in rabbits when administered at doses exceeding 50 µg per eye.³ 2-AG ether increases aqueous humor outflow via the CB₁ receptor in the trabecular meshwork.⁴

1 Hanus, L., Abu-Lafi, S., Fride, E., et al. 2-Arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB₁ receptor. Proc Natl Acad Sci USA 98 3662-3665 (2001).

2 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 2794-2801 (1999).

3 Laine, K., Jarvinen, K., Mechoulam, R., et al. Comparison of the enzymatic stability and intraocular pressure effects of 2-arachidonylglycerol and noladin ether, a novel putative endocannabinoid. Invest Ophthamol Vis Sci 43(10) 3216-3222 (2002 Oct 1).

4 Njie, Y.F., Kumar, A., Qiao, Z., et al. Noladin ether acts on trabecular meshwork cannabinoid (CB₁) receptors to enhance aqueous humor outflow facility. Invest Ophthamol Vis Sci 47(5) 1999-2005 (2006).

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 2794-2801 (1999).

Hanus, L., Abu-Lafi, S., Fride, E., et al. 2-Arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB₁ receptor. Proc Natl Acad Sci USA 98 3662-3665 (2001).

Laine, K., Jarvinen, K., Mechoulam, R., et al. Comparison of the enzymatic stability and intraocular pressure effects of 2-arachidonylglycerol and noladin ether, a novel putative endocannabinoid. Invest Ophthamol Vis Sci 43(10) 3216-3222 (2002 Oct 1).

Njie, Y.F., Kumar, A., Qiao, Z., et al. Noladin ether acts on trabecular meshwork cannabinoid (CB₁) receptors to enhance aqueous humor outflow facility. Invest Ophthamol Vis Sci 47(5) 1999-2005 (2006).

Show all 4 Hide all but first 3

2-Arachidonyl Glycerol ether is available in the following screening library:

• Bio-active Lipid I Screening Library (96-Well)