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Metabolism of N-acylethanolamines: To Phase II and Back Again
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
2017 (English)In: eLS, ISSN 1618-2863, article id 10.1002/9780470015902.a0027664Article, review/survey (Refereed) Epub ahead of print
Abstract [en]

N-acylethanolamines (NAEs) are a family of endogenous signalling molecules involved in various effects of the body including pain, inflam- mation, appetite and sleep. NAEs are mainly degraded by fatty acid amide hydrolase (FAAH) andN-acylethanolamine acid amidase (NAAA). FAAH inhibitors have shown promising results in pre- clinical studies of pain, inflammation and anxiety, mediating effects mainly via increased cannabi- noid receptor activity. However, FAAH inhibitors have failed in clinical pain trials, and in a recent phase I trial, an irreversible compound caused one death and sustained impairments in healthy vol- unteers. The latter is most likely due to off-target effects of that compound, rather than an FAAH-mediated effect, and design of dual-action FAAH-NAAA, -TRPV1 or -cyclooxygenase-2 inhibitory compounds may solve the pain efficacy issue. NAAA inhibitors are still in preclinical testing and show a promising anti-inflammatory profile mainly due to increased palmitoylethanolamide and oleoylethanolamide levels.

Place, publisher, year, edition, pages
Chichester: John Wiley & Sons, 2017. article id 10.1002/9780470015902.a0027664
National Category
Pharmacology and Toxicology
Research subject
Pharmaceutical Pharmacology
Identifiers
URN: urn:nbn:se:umu:diva-158344DOI: 10.1002/9780470015902.a0027664OAI: oai:DiVA.org:umu-158344DiVA, id: diva2:1306690
Available from: 2019-04-24 Created: 2019-04-24 Last updated: 2019-04-25

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