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The potential of inhibitors of endocannabinoid metabolism for drug development: A critical review

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Abstract

The endocannabinoids anandamide and 2-arachidonoylglycerol are metabolised by both hydrolytic enzymes (primarily fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL)) and oxygenating enzymes (e.g. cyclooxygenase- 2, COX-2). In the present article, the in vivo data for compounds inhibiting endocannabinoid metabolism have been reviewed, focussing on inflammation and pain. Potential reasons for the failure of an FAAH inhibitor in a clinical trial in patients with osteoarthritic pain are discussed. It is concluded that there is a continued potential for compounds inhibiting endocannabinoid metabolism in terms of drug development, but that it is wise not to be unrealistic in terms of expectations of success.

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Fowler, C. J. (2015). The potential of inhibitors of endocannabinoid metabolism for drug development: A critical review. In Handbook of Experimental Pharmacology (Vol. 231, pp. 95–128). Springer New York LLC. https://doi.org/10.1007/978-3-319-20825-1_4

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