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ChemMedChem. 2016 Jun 20;11(12):1242-51. doi: 10.1002/cmdc.201500395. Epub 2015 Oct 21.

A Double Whammy: Targeting Both Fatty Acid Amide Hydrolase (FAAH) and Cyclooxygenase (COX) To Treat Pain and Inflammation.

Author information

1
Department of Drug Discovery and Development, Fondazione Istituto Italiano di Tecnologia, via Morego 30, 16163, Genoa, Italy.
2
Department of Drug Discovery and Development, Fondazione Istituto Italiano di Tecnologia, via Morego 30, 16163, Genoa, Italy. daniele.piomelli@iit.it.
3
Departments of Anatomy and Neurobiology, Pharmacology and Biological Chemistry, University of California, Irvine, CA, 92697-4625, USA. daniele.piomelli@iit.it.

Abstract

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.

KEYWORDS:

drug design; enzymes; inflammation; multitarget inhibitors; pain; structure-activity relationships

PMID:
26486424
PMCID:
PMC4840092
DOI:
10.1002/cmdc.201500395
[Indexed for MEDLINE]
Free PMC Article

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