A Reversible and Selective Inhibitor of Monoacylglycerol Lipase Ameliorates Multiple Sclerosis1. Issue 50 (8th October 2014)

• Record Type: Journal Article
• Authors: Hernández‐Torres, Gloria; Cipriano, Mariateresa; Hedén, Erika; Björklund, Emmelie; Canales, Ángeles; Zian, Debora; Feliú, Ana; Mecha, Miriam; Guaza, Carmen; Fowler, Christopher J.; Ortega‐Gutiérrez, Silvia; López‐Rodríguez, María L.
• Is Part Of: Angewandte Chemie international edition. Volume 53:Issue 50(2014)
• Page Start: 13765
• Page End: 13770
• Publication Date: 2014-10-08
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201407807
• Languages: English
• ISSNs: 1433-7851

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Monoacylglycerol lipase (MAGL) is the enzyme responsible for the inactivation of the endocannabinoid 2‐arachidonoylglycerol (2‐AG). MAGL inhibitors show analgesic and tissue‐protecting effects in several disease models. However, the few efficient and selective MAGL inhibitors described to date block the enzyme irreversibly, and this can lead to pharmacological tolerance. Hence, additional classes of MAGL inhibitors are needed to validate this enzyme as a therapeutic target. Here we report a potent, selective, and reversible MAGL inhibitor (IC₅₀=0.18 μ<sc>M</sc>) which is active in vivo and ameliorates the clinical progression of a multiple sclerosis (MS) mouse model without inducing undesirable CB₁‐mediated side effects. These results support the interest in MAGL as a target for the treatment of MS.</p> </abstract>