Docosahexaenoyl Ethanolamide-d4

Docosahexaenoyl ethanolamide-d₄ contains four deuterium atoms at the 1, 1', 2, and 2' positions. It is intended for use as an internal standard for the quantification of docosahexaenoyl ethanolamide by GC- or LC-mass spectrometry (MS). Docosahexaenoic Acid (DHA) is an essential fatty acid and the most abundant ω-3 fatty acid in neural tissues, especially in the retina and brain. Docosahexaenoyl ethanolamide (DHEA) is the ethanolamine amide of DHA that has been detected in both brain and retina at concentrations similar to those for arachidonoyl ethanolamide (AEA).^1,2 A 9.5 fold increase of DHEA was observed in brain lipid extracts from piglets fed a diet supplemented with DHA compared to a control diet without DHA.³ DHEA binds to the rat brain CB₁ receptor with a K_i value of 324 nM, which is approximately 10-fold higher than the K_i value for AEA.⁴ DHEA inhibits shaker-related voltage-gated potassium channels in brain slightly better than AEA, with an IC₅₀ value of 1.5 μM.⁵

Synaptamide-d4 is labelled Synaptamide (S910000) which is an endocannabinoid-like derivative of docosahexaenoic acid with cannabinoid-independent function. It has potent synaptogenic activity and structural similarity to anandamide. Synaptamide (S910000) is subjected to hydrolysis by fatty acid amide hydrolase, and can be oxygenated to bioactive metabolites.

1. Sugiura, T., Kondo, S., Sukagawa, A., et al. Transacylase-mediated and phosphodiesterase-mediated synthesis of N-arachidonoylethanolamine, an endogenous cannabinoid-receptor ligand, in rat brain microsomes. Comparison with synthesis from free arachidonic acid and ethanolamine Eur. J. Biochem. 240,53-62(1996).
2. Bisogno, T., Delton-Vandenbroucke, I., Milone, A., et al. Biosynthesis and inactivation of N-Arachidonoylethanolamine (Ananadamide) and N-Docosahexaenoylethanolamine in bovine retina Arch. Biochem. Biophys. 370(2),300-307(1999).
3. Berger, A., Crozier, G., Bisogno, T., et al. Anandamide and diet: Inclusion of dietary arachidonate and docosahexaenoate leads to increased brain levels of the corresponding N-acylethanolamines in piglets Proc. Natl. Acad. Sci. USA 98(11),6402-6406(2001).
4. Sheskin, T., Hanus, L., Slager, J., et al. Structural requirements for binding of anandamide-type compounds to the brain cannabinoid receptor J. Med. Chem. 40,659-667(1997).
5. Poling, J.S., Rogawski, M.A., Salem, N., Jr., et al. Anadamide, an endogenous cannabinoid, inhibits shaker-related voltage-gated K⁺ channels Neuropharmacology 35(7),983-991(1996).