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].
[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).