Palmitoyl Ethanolamide

Palmitoyl ethanolamide (PEA) is an endogenous fatty N-acyl ethanolamine and a derivative of the endocannabinoid arachidonoyl ethanolamide (AEA; Item No. 90050).^1,2 It selectively activates peroxisome proliferator-activated receptor α (PPARα; EC₅₀ = 3.1 µM) over PPARβ/δ and PPARγ in HeLa cells expressing the human receptors.³ PEA binds to RBL-2H3 basophil membranes (IC₅₀ = 1 nM), which endogenously express cannabinoid 2 (CB₂), but not CB₁, receptors, and inhibits antigen-induced serotonin release from RBL-2H3 cells (EC₅₀ = 0.27 µM).² It prevents decreases in paw withdrawal latency in a radiant heat hypersensitivity test, an effect that can be reversed by the CB₁ receptor antagonist SR141716 (rimonabant; Item No. 9000484), PPARγ antagonist GW 9662 (Item No. 70785), and transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine (Item No. 10007518), in a mouse model of neuropathic pain induced by chronic constriction injury of the sciatic nerve.⁴ PEA (10 mg/kg) decreases carrageenan-induced paw edema in wild-type, but not Ppara^-/-, mice.³ It inhibits tonic convulsions induced by pentylenetetrazole (PTZ; Item No. 18682) in rats when administered at a dose of 40 mg/kg.⁵ Formulations containing palmitoyl ethanolamide have been used as dietary supplements.

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1. Bachur, N.R., Masek, K., Melmon, K.L., et al. Fatty acid amides of ethanolamine in mammalian tissues. The Journal of Biological Chemisty 240, 1019-1024 (1965).

2. Facci, L., Dal Toso, R., Romanello, S., et al. Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide. Proc. Natl. Acad. Sci. USA 92(8), 3376-3380 (1995).

3. Lo Verme, J., Fu, J., Astarita, G., et al. The nuclear receptor peroxisome proliferator-activated receptor-α mediates the anti-inflammatory actions of palmitoylethanolamide. Mol. Pharmacol. 67(1), 15-19 (2005).

4. Costa, B., Comelli, F., Bettoni, I., et al. The endogenous fatty acid amide, palmitoylethanolamide, has anti-allodynic and anti-hyperalgesic effects in a murine model of neuropathic pain: Involvement of CB₁, TRPV1 and PPARγ receptors and neurotrophic factors. Pain 139(3), 541-550 (2008).

5. Sheerin, A.H., Zhang, X., Saucier, D.M., et al. Selective antiepileptic effects of N-palmitoylethanolamide, a putative endocannabinoid. Epilepsia 45(10), 1184-1188 (2004).

Kantae, V., Ogino, S., Noga, M., et al. Quantitative profiling of endocannabinoids and related N-acylethanolamines in human CSF using nano LC-MS/MS. J. Lipid. Res. 58(3), 615-624 (2017).

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).

Costa, B., Comelli, F., Bettoni, I., et al. The endogenous fatty acid amide, palmitoylethanolamide, has anti-allodynic and anti-hyperalgesic effects in a murine model of neuropathic pain: Involvement of CB₁, TRPV1 and PPARγ receptors and neurotrophic factors. Pain 139(3), 541-550 (2008).