Linoleoyl Ethanolamide

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 K_i 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 K_i value of 9.0 µM, but also is hydrolyzed effectively by the enzyme.^6,7

WARNING This product is not for human or veterinary use.

1. Patrono, C., Rotella, C.M., Toccafondi, R.S., et al. Prostacyclin stimulates the adenylate cyclase system of human thyroid tissue. Prostaglandins 22(1), 105-115 (1981).

2. Schmid, P.C., Kuwae, T., Krebsbach, R.J., et al. Anandanide and other N-acylethanolamines in mouse peritoneal macrophages. Chem. Phys. 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. J. Med. Chem. 41(27), 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. Biol. Pharm. Bull. 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. Biochem. J. 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).

Gouveia-Figueira, S., Karlsson, J., Deplano, A., et al. Characterisation of (R)-2-(2-fluorobiphenyl-4-yl)-N-(3-methylpyridin-2-yl)propanamide as a dual fatty acid amide hydrolase: Cyclooxygenase inhibitor. PLoS One 10(9), e0139212 (2015).