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Potential analgesic effects of a novel N-acylethanolamine acid amidase inhibitor F96 through PPAR-α
Pharmacological blockade of N-acylethanolamine acid amidase (NAAA) activity is an available approach for inflammation and pain control through restoring the ability of endogenous PEA. But the recently reported NAAA inhibitors suffer from the chemical and biological unstable properties, which restric...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550851/ https://www.ncbi.nlm.nih.gov/pubmed/26310614 http://dx.doi.org/10.1038/srep13565 |
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author | Yang, Longhe Li, Long Chen, Ling Li, Yanting Chen, Huixia Li, Yuhang Ji, Guangnian Lin, Donghai Liu, Zuguo Qiu, Yan |
author_facet | Yang, Longhe Li, Long Chen, Ling Li, Yanting Chen, Huixia Li, Yuhang Ji, Guangnian Lin, Donghai Liu, Zuguo Qiu, Yan |
author_sort | Yang, Longhe |
collection | PubMed |
description | Pharmacological blockade of N-acylethanolamine acid amidase (NAAA) activity is an available approach for inflammation and pain control through restoring the ability of endogenous PEA. But the recently reported NAAA inhibitors suffer from the chemical and biological unstable properties, which restrict functions of NAAA inhibition in vivo. It is still unrevealed whether systematic inhibition of NAAA could modulate PEA-mediated pain signalings. Here we reported an oxazolidinone imide compound 3-(6-phenylhexanoyl) oxazolidin-2-one (F96), which potently and selectively inhibited NAAA activity (IC(50) = 270 nM). Intraperitoneal (i.p.) injection of F96 (3–30 mg/kg) dose-dependently reduced ear edema and restored PEA levels of ear tissues in 12-O-Tetradecanoylphorbol-13-acetate (TPA) induced ear edema models. Furthermore, F96 inhibited acetic acid-induced writhing and increased spared nerve injury induced tactile allodynia thresholds in a dose-dependent manner. Pharmacological effects of F96 (10 mg/kg, i.p.) on various animal models were abolished in PPAR-α(−/−) mice, and were prevented by PPAR-α antagonist MK886 but not by canabinoid receptor type 1 (CB(1)) antagonist Rimonabant nor canabinoid receptor type 2 (CB(2)) antagonist SR144528. Zebrafish embryos experiments showed better security and lower toxicity for F96 than ibuprofen. These results revealed that F96 might be useful in treating inflammatory and neuropathic pain by NAAA inhibition depending on PPAR-α receptors. |
format | Online Article Text |
id | pubmed-4550851 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45508512015-09-04 Potential analgesic effects of a novel N-acylethanolamine acid amidase inhibitor F96 through PPAR-α Yang, Longhe Li, Long Chen, Ling Li, Yanting Chen, Huixia Li, Yuhang Ji, Guangnian Lin, Donghai Liu, Zuguo Qiu, Yan Sci Rep Article Pharmacological blockade of N-acylethanolamine acid amidase (NAAA) activity is an available approach for inflammation and pain control through restoring the ability of endogenous PEA. But the recently reported NAAA inhibitors suffer from the chemical and biological unstable properties, which restrict functions of NAAA inhibition in vivo. It is still unrevealed whether systematic inhibition of NAAA could modulate PEA-mediated pain signalings. Here we reported an oxazolidinone imide compound 3-(6-phenylhexanoyl) oxazolidin-2-one (F96), which potently and selectively inhibited NAAA activity (IC(50) = 270 nM). Intraperitoneal (i.p.) injection of F96 (3–30 mg/kg) dose-dependently reduced ear edema and restored PEA levels of ear tissues in 12-O-Tetradecanoylphorbol-13-acetate (TPA) induced ear edema models. Furthermore, F96 inhibited acetic acid-induced writhing and increased spared nerve injury induced tactile allodynia thresholds in a dose-dependent manner. Pharmacological effects of F96 (10 mg/kg, i.p.) on various animal models were abolished in PPAR-α(−/−) mice, and were prevented by PPAR-α antagonist MK886 but not by canabinoid receptor type 1 (CB(1)) antagonist Rimonabant nor canabinoid receptor type 2 (CB(2)) antagonist SR144528. Zebrafish embryos experiments showed better security and lower toxicity for F96 than ibuprofen. These results revealed that F96 might be useful in treating inflammatory and neuropathic pain by NAAA inhibition depending on PPAR-α receptors. Nature Publishing Group 2015-08-27 /pmc/articles/PMC4550851/ /pubmed/26310614 http://dx.doi.org/10.1038/srep13565 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Yang, Longhe Li, Long Chen, Ling Li, Yanting Chen, Huixia Li, Yuhang Ji, Guangnian Lin, Donghai Liu, Zuguo Qiu, Yan Potential analgesic effects of a novel N-acylethanolamine acid amidase inhibitor F96 through PPAR-α |
title | Potential analgesic effects of a novel N-acylethanolamine acid amidase inhibitor F96 through PPAR-α |
title_full | Potential analgesic effects of a novel N-acylethanolamine acid amidase inhibitor F96 through PPAR-α |
title_fullStr | Potential analgesic effects of a novel N-acylethanolamine acid amidase inhibitor F96 through PPAR-α |
title_full_unstemmed | Potential analgesic effects of a novel N-acylethanolamine acid amidase inhibitor F96 through PPAR-α |
title_short | Potential analgesic effects of a novel N-acylethanolamine acid amidase inhibitor F96 through PPAR-α |
title_sort | potential analgesic effects of a novel n-acylethanolamine acid amidase inhibitor f96 through ppar-α |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550851/ https://www.ncbi.nlm.nih.gov/pubmed/26310614 http://dx.doi.org/10.1038/srep13565 |
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