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Dual Inhibition of alpha/beta-hydrolase Domain 6 and Fatty Acid Amide Hydrolase Increases Endocannabinoid Levels in Neurons

Dual Inhibition of alpha/beta-hydrolase Domain 6 and Fatty Acid Amide Hydrolase Increases Endocannabinoid Levels in Neurons

William R Marrs, Eric A Horne, Silvia Ortega-Gutierrez, Jose Antonio Cisneros, Cong Xu, Yi Hsing Lin, Giulio G Muccioli, Maria L Lopez-Rodriguez, Nephi Stella

J Biol Chem. 2011 Aug 19;286(33):28723-8.

PMID: 21665953

Abstract:

Agonists at cannabinoid receptors, such as the phytocannabinoid Δ(9)-tetrahydrocannabinol, exert a remarkable array of therapeutic effects but are also associated with undesirable psychoactive side effects. Conversely, targeting enzymes that hydrolyze endocannabinoids (eCBs) allows for more precise fine-tuning of cannabinoid receptor signaling, thus providing therapeutic relief with reduced side effects. Here, we report the development and characterization of an inhibitor of eCB hydrolysis, UCM710, which augments both N-arachidonoylethanolamine and 2-arachidonoylglycerol levels in neurons. This compound displays a unique pharmacological profile in that it inhibits fatty acid amide hydrolase and α/β-hydrolase domain 6 but not monoacylglycerol lipase. Thus, UCM710 represents a novel tool to delineate the therapeutic potential of compounds that manipulate a subset of enzymes that control eCB signaling.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP213738773	UCM710		213738-77-3	Price

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