Numerous analogs of arachidonoyl ethanolamide (AEA) potentiate its biological activity.1 This potentiation is ascribed either to inhibition of AEA reuptake into neurons, or inhibition of fatty acid amide hydrolase (FAAH) within the neurons.2 AM1172 is an endocannabinoid analog specifically designed to be a potent and selective inhibitor of AEA uptake that is resistant to FAAH hydrolysis.3 Structurally, AM1172 is the “reversed” isomer of AM404, constructed using arachidonyl amine; this may account for its metabolic stability. In mouse cortical neurons, AM1172 blocked the uptake of tritiated AEA with an EC50 of about 1.5 µM.3
1
Khanolkar, A.D., and Makriyannis, A. Structure-activity relationships of anandamide, an endogenous cannabinoid ligand. Life Sci65607-616(1999).
2
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).
3
Fegley, D., Kathuria, S., Mercier, R., et al. Anandamide transport is independent of fatty-acid amide hydrolase activity and is blocked by the hydrolysis-resistant inhibitor AM1172. Proc Natl Acad Sci USA101(23)8756-8761(2004).
Khanolkar, A.D., and Makriyannis, A. Structure-activity relationships of anandamide, an endogenous cannabinoid ligand. Life Sci65607-616(1999).
Fegley, D., Kathuria, S., Mercier, R., et al. Anandamide transport is independent of fatty-acid amide hydrolase activity and is blocked by the hydrolysis-resistant inhibitor AM1172. Proc Natl Acad Sci USA101(23)8756-8761(2004).
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).
AM1172 is available in the following screening
library: