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Issue 19, 2014
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Chemical approaches to therapeutically target the metabolism and signaling of the endocannabinoid 2-AG and eicosanoids

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Abstract

The endocannabinoid system, most popularly known as the target of the psychoactive component of marijuana, Δ9-tetrahydrocannabinol (THC), is a signaling network that modulates a diverse range of physiological processes including nociception, behavior, cognitive function, appetite, metabolism, motor control, memory formation, and inflammation. While THC and its derivatives have garnered notoriety in the eyes of the public, the endocannabinoid system consists of two endogenous signaling lipids, 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (anandamide), which activate cannabinoid receptors CB1 and CB2 in the nervous system and peripheral tissues. This review will focus on the recent efforts to chemically manipulate 2-AG signaling through the development of inhibitors of the 2-AG-synthesizing enzyme diacylglycerol lipase (DAGL) or the 2-AG-degrading enzyme monoacylglycerol lipase (MAGL), and assessing the therapeutic potential of DAGL and MAGL inhibitors in pain, inflammation, degenerative diseases, tissue injury, and cancer.

Graphical abstract: Chemical approaches to therapeutically target the metabolism and signaling of the endocannabinoid 2-AG and eicosanoids

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Publication details

The article was received on 27 Jan 2014 and first published on 28 Mar 2014


Article type: Review Article
DOI: 10.1039/C4CS00047A
Author version available: Download Author version (PDF)
Citation: Chem. Soc. Rev., 2014,43, 6859-6869
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    Chemical approaches to therapeutically target the metabolism and signaling of the endocannabinoid 2-AG and eicosanoids

    R. A. Kohnz and D. K. Nomura, Chem. Soc. Rev., 2014, 43, 6859
    DOI: 10.1039/C4CS00047A

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