CAY10412

Anandamide (arachidonoyl ethanolamide; AEA) is an endogenous lipid with cannabinergic activity; along with 2-arachidonoyl glycerol, it forms part of the endocannabinoid system.^1,2 AEA undergoes reuptake into neurons by a facilitated process.³ Controversy exists as to whether there is a specific AEA transporter, or instead the uptake process is simply driven by hydrolysis of AEA by intracellular fatty acyl amide hydrolase (FAAH).^4,5 CAY10412 is an analog of AEA that has no intrinsic binding affinity for either CB₁ or CB₂ receptors.⁶ It is a potent inhibitor of AEA reuptake in U937 lymphoma cells, with an IC₅₀ of 3 µM.⁶ CAY10412 could be a useful tool for distinguishing the competing transporter theories. The pharmacology of CAY10412 is largely unexplored; it may enhance endocannabinoid signalling by augmenting endocannabinoid concentrations.

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1. Devane, W.A., Hanus, L., Breuer, A., et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258(5090), 1946-1949 (1992).

2. Felder, C.C., Briley, E.M., Axelrod, J., et al. Anandamide, an endogenous cannabimimetic eicosanoid, binds to the cloned human cannabinoid receptor and stimulates receptor-mediated signal transduction. Proc. Natl. Acad. Sci. USA 90(16), 7656-7660 (1993).

3. Deutsch, D.G., Glaser, S.T., Howell, J.M., et al. The cellular uptake of anandamide is coupled to its breakdown by fatty-acid amide hydrolase. The Journal of Biological Chemisty 276(10), 6967-6973 (2001).

4. Beltramo, M., Stella, N., Calignano, A., et al. Functional role of high-affinity anandamide transport, as revealed by selective inhibition. Science 277(5329), 1094-1097 (1997).

5. Glaser, S.T., Abumrad, N.A., Fatade, F., et al. Evidence against the presence of an anandamide transporter. Proc. Natl. Acad. Sci. USA 100(7), 4269-4274 (2003).

6. López-Rodriguez, M.L., Viso, A., Ortega-Gutiérrez, S., et al. Design, synthesis and biological evaluation of novel arachidonic acid derivatives as highly potent and selective endocannabinoid transporter inhibitors. J. Med. Chem. 44(26), 4505-4508 (2001).