Linoleoyl ethanolamide-d₄contains four deuterium atoms at the hydroxyethyl 1,1',2, and 2' positions. It is intended for use as an internal standard for the quantification of linoleoyl ethanolamide by GC-or LC-mass spectrometry. Linoleoyl ethanolamide is an endocannabinoid detected in porcine brain and murine peritoneal macrophages which contains linoleate in place of the arachidonate moiety of arachidonoyl ethanolamide (AEA).^1,2It has weak affinity for the central cannabinoid (CB₁) and peripheral cannabinoid (CB₂) receptors, exhibiting K_ivalues of 10 µM and 25 µM, respectively.³However, it is only approximately 4-fold less potent than AEA at causing catalepsy in mice (ED₅₀of 26.5 mg/kg).⁴In addition, linoleoyl ethanolamide increases ERK phosphorylation and AP-1-dependent transcription approximately 1.5-fold at 15 µM in a CB-receptor-independent manner.⁵However, cellular toxicity is readily apparent at concentrations of 10-20 µM. Linoleoyl ethanolamide inhibits human fatty acid amide hydrolase-dependent hydrolysis of AEA with a K_ivalue of 9.0 µM, but also is hydrolyzed effectively by the enzyme.^6,7

1.Patrono, C., Rotella, C.M., Toccafondi, R.S., et al.Prostacyclin stimulates the adenylate cyclase system of human thyroid tissueProstaglandins22(1)105-115(1981) 2.Schmid, P.C., Kuwae, T., Krebsbach, R.J., et al.Anandanide and other N-acylethanolamines in mouse peritoneal macrophagesChemistry and Physics of Lipids87103-110(1997) 3.Lin, S., Khanolkar, A.D., Fan, P., et al.Novel analogues of arachidonylethanolamide (anandamide): Affinities for the CB1 and CB2 cannabinoid receptors and metabolic stabilityJournal of Medicinal Chemistry415353-5361(1998) 4.Watanabe, K., Matsunaga, T., Nakamura, S., et al.Pharmacological effects in mice of anandamide and its related fatty acid ethanolamides, and enhancement of cataleptogenic effect of anandamide by phenylmethylsulfonyl fluorideBiological and Pharmaceutical Bullentin22(4)366-370(1999) 5.Berdyshev, E.V., Schmid, P.C., Krebsbach, R.J., et al.Cannabinoid-receptor-independent cell signalling by N-acylethanolaminesBiochemistry Journal36067-75(2001) 6.Maccarrone, M., van der Stelt, M., Rossi, A., et al.Anandamide hydrolysis by human cells in culture and brainThe Journal of Biological Chemisty27332332-32339(1998) 7.Bisogno, T., Maurelli, S., Melck, D., et al.Biosynthesis, uptake, and degradation of anandamide and palmitoylethanolamide in leukocytesThe Journal of Biological Chemisty2723315-3323(1997)