2-Arachidonyl Glycerol ether

2-Arachidonyl glycerol ether (2-AG ether) selectively binds to cannabinoid (CB) receptor 1 (K_is = 21.2 and >3,000 nM for CB₁ and CB₂, respectively, in a radioligand binding assay).¹ It is a potent and selective agonist of CB₁ and GPR55 with EC₅₀ values of 10, 37, and >30,000 nM for CB₁, GPR55, and CB₂, respectively.² 2-AG ether displays the typical tetrad of CB activities in mice.¹ It is more chemically stable than 2-AG (Item No. 62160), 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.⁴ 2-AG ether elicits modest reductions in intraocular pressure in rabbits when administered at doses exceeding 50 µg per eye.³ It increases aqueous humor outflow via the CB₁ receptor in the trabecular meshwork.⁵ Administration of 2-AG ether to the nucleus accumbens (0.0625-1 μg) increases dietary intake and enhances fat consumption in rats given access to both high-carbohydrate and high-fat diets.⁶

WARNING This product is not for human or veterinary use.

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(7), 3662-3665 (2001).

2. Ryberg, E., Larsson, N., Sjögren, S., et al. The orphan receptor GPR55 is a novel cannabinoid receptor. Br. J. Pharmacol. 152(7), 1092-1101 (2007).

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. Ophthalmol. Vis. Sci. 43(10), 3216-3222 (2002).

4. 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. The Journal of Biological Chemisty 274(5), 2794-2801 (1999).

5. 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. Ophthalmol. Vis. Sci. 47(5), 1999-2005 (2006).

6. Deshmukh, R.R., and Sharma, P.L. Stimulation of accumbens shell cannabinoid CB₁ receptors by noladin ether, a putative endocannabinoid, modulates food intake and dietary selection in rats. Pharmacol. Res. 66(3), 276-282 (2012).

Caires, R., Sierra-Valdez, F.J., Millet, J.R.M., et al. Omega-3 fatty acids modulate TRPV4 function through plasma membrane remodeling. Cell Reports 21, 245-258 (2017).