Unknown

Dataset Information

0

Dual inhibition of alpha/beta-hydrolase domain 6 and fatty acid amide hydrolase increases endocannabinoid levels in neurons.

ABSTRACT: Agonists at cannabinoid receptors, such as the phytocannabinoid ?(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 ?/?-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.

SUBMITTER: Marrs WR 

PROVIDER: S-EPMC3190680 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Dual inhibition of alpha/beta-hydrolase domain 6 and fatty acid amide hydrolase increases endocannabinoid levels in neurons.

Marrs William R WR   Horne Eric A EA   Ortega-Gutierrez Silvia S   Cisneros Jose Antonio JA   Xu Cong C   Lin Yi Hsing YH   Muccioli Giulio G GG   Lopez-Rodriguez Maria L ML   Stella Nephi N  

The Journal of biological chemistry 20110610 33

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, UCM7  ...[more]

Similar Datasets

Unknown Design and Potency of Dual Soluble Epoxide Hydrolase/Fatty Acid Amide Hydrolase Inhibitors.
| S-EPMC6210075 | biostudies-literature
Unknown Equipotent inhibition of fatty acid amide hydrolase and monoacylglycerol lipase - dual targets of the endocannabinoid system to protect against seizure pathology.
| S-EPMC3480564 | biostudies-literature
Unknown Optimization of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.
| S-EPMC2734917 | biostudies-literature
Unknown Identification and optimization of soluble epoxide hydrolase inhibitors with dual potency towards fatty acid amide hydrolase.
| S-EPMC5837813 | biostudies-literature
Unknown Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.
| S-EPMC2531194 | biostudies-literature
Unknown The Molecular Basis for Dual Fatty Acid Amide Hydrolase (FAAH)/Cyclooxygenase (COX) Inhibition.
| S-EPMC5063142 | biostudies-literature
Unknown α-Ketoheterocycle-based Inhibitors of Fatty Acid Amide Hydrolase (FAAH).
| S-EPMC3359644 | biostudies-other
Unknown Experimental colitis in mice is attenuated by changes in the levels of endocannabinoid metabolites induced by selective inhibition of fatty acid amide hydrolase (FAAH).
| S-EPMC4136976 | biostudies-literature
Transcriptomics Overexpression of fatty acid amide hydrolase induces early flowering in Arabidopsis thaliana
2012-02-01 | E-MEXP-3486 | biostudies-arrayexpress
Unknown Inhibition of fatty acid amide hydrolase prevents pathology in neurovisceral acid sphingomyelinase deficiency by rescuing defective endocannabinoid signaling.
| S-EPMC7645369 | biostudies-literature