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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.
1
Devane, W.A., Hanus, L., Breuer, A., et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science2581946-1949(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 USA907656-7660(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. J Biol Chem276(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. Science2771094-1097(1997).
5
Glaser, S.T., Abumrad, N.A., Fatade, F., et al. Evidence against the presence of an anandamide transporter. Proc Natl Acad Sci USA100(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 Chem444505-4508(2001).
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in continental US; may vary elsewhere
SMILES
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CCCCC/C=C\C/C=C\C/C=C\C/C=C\CCCC(=O)OCc1cscc1
Background Reading
Devane, W.A., Hanus, L., Breuer, A., et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science2581946-1949(1992).
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 USA907656-7660(1993).
Beltramo, M., Stella, N., Calignano, A., et al. Functional role of high-affinity anandamide transport, as revealed by selective inhibition. Science2771094-1097(1997).
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 Chem444505-4508(2001).
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. J Biol Chem276(10)6967-6973(2001).
Glaser, S.T., Abumrad, N.A., Fatade, F., et al. Evidence against the presence of an anandamide transporter. Proc Natl Acad Sci USA100(7)4269-4274(2003).