(R)-N-(1-Methyl-2-hydroxyethyl)-13-(S)-methyl-arachidonamide (AMG315): A Novel Chiral Potent Endocannabinoid Ligand with Stability to Metabolizing Enzymes

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Dow P. Hurst, Research Scientist (Creator)
Patricia H. Reggio, Professor and Department Head (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/

Abstract: The synthesis of potent metabolically stable endocannabinoids is challenging. Here we report a chiral arachidonoyl ethanolamide (AEA) analogue, namely, (13S,1'R)-dimethylanandamide (AMG315, 3a), a high affinity ligand for the CB1 receptor (Ki of 7.8 ± 1.4 nM) that behaves as a potent CB1 agonist in vitro (EC50 = 0.6 ± 0.2 nM). (13S,1'R)-dimethylanandamide is the first potent AEA analogue with significant stability for all endocannabinoid hydrolyzing enzymes as well as the oxidative enzymes COX-2. When tested in vivo using the CFA-induced inflammatory pain model, 3a behaved as a more potent analgesic when compared to endogenous AEA or its hydrolytically stable analogue AM356. This novel analogue will serve as a very useful endocannabinoid probe.

Additional Information

Publication
Journal of Medicinal Chemistry, 61(19), 8639-8657
Language: English
Date: 2018
Keywords
endocannabinoids, novel chiral ligand, arachidonoyl ethanolamide (AEA) analogue

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