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A Double Whammy : Targeting Both Fatty Acid Amide Hydrolase (FAAH) and Cyclooxygenase (COX) To Treat Pain and Inflammation
Author(s) -
Scarpelli Rita,
Sasso Oscar,
Piomelli Daniele
Publication year - 2016
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201500395
Subject(s) - fatty acid amide hydrolase , inflammation , endocannabinoid system , cyclooxygenase , anandamide , pharmacology , medicine , arthritis , analgesic , chemistry , immunology , cannabinoid receptor , antagonist , biochemistry , enzyme , receptor
Pain states that arise from non‐resolving inflammation, such as inflammatory bowel disease or arthritis, pose an unusually difficult challenge for therapy because of the complexity and heterogeneity of their underlying mechanisms. It has been suggested that key nodes linking interactive pathogenic pathways of non‐resolving inflammation might offer novel targets for the treatment of inflammatory pain. Nonsteroidal anti‐inflammatory drugs (NSAIDs), which inhibit the cyclooxygenase (COX)‐mediated production of pain‐ and inflammation‐inducing prostanoids, are a common first‐line treatment for this condition, but their use is limited by mechanism‐based side effects. The endogenous levels of anandamide, an endocannabinoid mediator with analgesic and tissue‐protective functions, are regulated by fatty acid amide hydrolase (FAAH). This review outlines the pharmacological and chemical rationale for the simultaneous inhibition of COX and FAAH activities with designed multitarget agents. Preclinical studies indicate that such agents may combine superior anti‐inflammatory efficacy with reduced toxicity.