Linoleoyl Ethanolamide (Synonyms: LEA)

Linoleoyl ethanolamide is an endocannabinoid detected in porcine brain and murine peritoneal macrophages which contains linoleate in place of the arachidonate moiety of arachidonyl ethanolamide (AEA). [1] [2] It has weak affinity for the cannabinoid 1 (CB1) and CB2 receptors, exhibiting Ki values of 10 µM and 25 µM, respectively.[3]  However, it is only approximately 4-fold less potent than AEA at causing catalepsy in mice (ED50 of 26.5 mg/kg). [4] In addition, linoleoyl ethanolamide increases ERK phosphorylation and AP-1-dependent transcription approximately 1.5 fold at 15 µM in a CB-receptor-independent manner.[5]  However, 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 Ki value of 9.0 µM, but also is hydrolyzed effectively by the enzyme. [6][7] 

Reference:
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[2]. Schmid, P.C., Kuwae, T., Krebsbach, R.J., et al. Anandanide and other N-acylethanolamines in mouse peritoneal macrophages. Chemistry and Physics of Lipids 87, 103-110 (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 stability. Journal of Medicinal Chemistry 41, 5353-5361 (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 fluoride. Biological and Pharmaceutical Bullentin 22(4), 366-370 (1999).
[5]. Berdyshev, E.V., Schmid, P.C., Krebsbach, R.J., et al. Cannabinoid-receptor-independent cell signalling by N-acylethanolamines. Biochemistry Journal 360, 67-75 (2001).
[6]. Maccarrone, M., van der Stelt, M., Rossi, A., et al. Anandamide hydrolysis by human cells in culture and brain. The Journal of Biological Chemisty 273, 32332-32339 (1998).
[7]. Bisogno, T., Maurelli, S., Melck, D., et al. Biosynthesis, uptake, and degradation of anandamide and palmitoylethanolamide in leukocytes. The Journal of Biological Chemisty 272, 3315-3323 (1997).