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Inhibitors of the Endocannabinoid-Degrading Enzymes, or how to Increase Endocannabinoid's Activity by Preventing their Hydrolysis.
MedLine Citation:
PMID:  22280341     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Endocannabinoids are lipid transmitters binding and activating the cannabinoid receptors. Both cannabinoid receptors and endocannabinoids, such as 2-arachidonoylglycerol and anandamide, have been shown to control numerous physiological and pathological processes, including in the central nervous system. Thus regulating endocannabinoid levels in-vivo represents an interesting therapeutic perspective in several CNS-related diseases. To date four enzymes - Fatty Acid Amide Hydrolase (FAAH), N-Acylethanolamine-hydrolyzing Acid Amidase (NAAA), Monoacylglycerol Lipase (MAGL), α/β-Hydrolase Domain 6 (ABHD6) - were shown to control endocannabinoid levels in tissues or in intact cells. While the searches for NAAA and ABHD6 inhibitors are still in their beginning, a growing number of selective and potent inhibitors are now available to inhibit FAAH and MAGL activities. Here, based on the literature and patent literature, we review the compounds of the different chemical families that have been developed to inhibit these enzymes, with a special emphasis on FAAH and MAGL inhibitors.
Authors:
Marion Feledziak; Didier M Lambert; Jacqueline Marchand-Brynaert; Giulio G Muccioli
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Recent patents on CNS drug discovery     Volume:  7     ISSN:  2212-3954     ISO Abbreviation:  Recent Pat CNS Drug Discov     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-01-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101265656     Medline TA:  Recent Pat CNS Drug Discov     Country:  United Arab Emirates    
Other Details:
Languages:  eng     Pagination:  49-70     Citation Subset:  IM    
Affiliation:
Universite catholique de Louvain, Louvain Drug Research Institute, Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Avenue E. Mounier 72, B1.72.01, B-1200 Bruxelles, Belgium. giulio.muccioli@uclouvain.be.
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