2. Academic Validation
  3. 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

  • J Biol Chem. 2011 Aug 19;286(33):28723-28728. doi: 10.1074/jbc.M110.202853.
William R Marrs 1,  Eric A Horne 2,  Silvia Ortega-Gutierrez 3,  Jose Antonio Cisneros 3,  Cong Xu 2,  Yi Hsing Lin 2,  Giulio G Muccioli 4,  Maria L Lopez-Rodriguez 3,  Nephi Stella 5
Affiliations

Affiliations

  • 1 Neurobiology and Behavior Graduate Program, University of Washington, Seattle, Washington 98195-7270.
  • 2 Department of Pharmacology, University of Washington, Seattle, Washington 98195-7280.
  • 3 Departamento de Química Orgánica I, Facultad de Ciencias Químicas, Universidad Complutense, 28040 Madrid, Spain.
  • 4 Bioanalysis and Pharmacology of Bioactive Lipids Laboratory, CHAM7230, Louvain Drug Research Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium, and.
  • 5 Department of Pharmacology, University of Washington, Seattle, Washington 98195-7280,; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington 98195-6560. Electronic address: nstella@uw.edu.
PMID: 21665953 DOI: 10.1074/jbc.M110.202853
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.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z