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N-(4-Methoxy-2-nitrophenyl)hexadecanamide, a palmitoylethanolamide analogue, reduces formalin-induced nociception
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
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2012 (English)In: Life Sciences, ISSN 0024-3205, E-ISSN 1879-0631, Vol. 91, no 25-26, 1288-1294 p.Article in journal (Refereed) Published
Abstract [en]

Aims: To investigate the local antinociceptive effect as well as the possible mechanisms of action of a novel analogue of palmitoylethanolamide (PEA) N-(4-methoxy-2-nitrophenyl)hexadecanamide (HD) in the rat formalin test.

Main methods: The formalin test was used to assess the antinociceptive activity of HD in vivo. The hydrolysis of anandamide catalyzed by fatty acid amide hydrolase (FAAH) was used to determine the action of HD on FAAH activity in vitro.

Key findings: Local peripheral ipisilateral, but not contralateral, administration of HD (10-100 mu g/paw) produced a dose-dependent antinociceptive effect in rats. The CB1 and CB2 receptor antagonists AM281 (0.3-30 mu g/paw) and SR144528 (0.3-30 mu g/paw), respectively, reduced the antinociceptive effect of HD (100 mu g/paw). In addition, methiothepin (0.03-0.3 mu g/paw) and naloxone (5-50 mu g/paw) significantly reduced HD-induced antinociception (100 mu g/paw). In vitro, HD reduced only to a minor extent the hydrolysis of anandamide catalyzed by FAAH.

Significance: HD local administration produces antinociception that probably results from an indirect activation of peripheral CB1 and CB2 cannabinoid receptors. Data suggest that 5-HT1 and opioid receptors also participate in the antinociceptive effect of this compound. HD may have potential as analgesic drug.

(C) 2012 Elsevier Inc. All rights reserved.

Place, publisher, year, edition, pages
2012. Vol. 91, no 25-26, 1288-1294 p.
Keyword [en]
N-(4-Methoxy-2-nitrophenyl)hexadecanamide Palmitoylethanolamide, Anandamide, Cannabinoid receptors, Antinociception, Fatty acid amide hydrolase
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:umu:diva-64037DOI: 10.1016/j.lfs.2012.09.024ISI: 000312361500007OAI: oai:DiVA.org:umu-64037DiVA: diva2:599827
Available from: 2013-01-22 Created: 2013-01-14 Last updated: 2017-12-06Bibliographically approved

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