Eicosapentaenoyl Serotonin

Eicosapentaenoyl serotonin is a hybrid molecule patterned after arachidonoyl serotonin. Arachidonoyl serotonin is an inhibitor of fatty acid amide hydrolase (FAAH) and also acts as an antagonist of transient receptor potential vanilloid-type 1 (TRPV1) channels. Arachidonoyl serotonin is analgesic, reducing both acute and chronic peripheral pain in rodents [1, 2]. The effects of replacement the arachidonoyl portion with eicosapentaenoic acid have not been investigated. Replacement of arachidonate with saturated 11- or 12-carbon fatty acids generated compounds that potently inhibited capsaicin-induced TRPV1 channel activation with an IC50 of 0.76 μM. This compound showed no effects on blocking FAAH-mediated hydrolysis of arachidonoyl ethanolamide with an IC50 of > 50 μM [1].

References:
[1] Ortar, G. ,Cascio, M.G.,De Petrocellis, L., et al. New N-arachidonoylserotonin analogues with potential "dual" mechanism of action against pain. Journal of Medicinal Chemistry 50, 6554-6569 (2007).
[2] Maione, S. ,De Petrocellis, L.,de Novellis, V., et al. Analgesic actions of N-arachidonoyl-serotonin, a fatty acid amide hydrolase inhibitor with antagonistic activity at vanilloid TRPV1 receptors. British Journal of Pharmacology 150, 766-781 (2007).