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The aim of this study was to deepen the pharmacological study of two new hybrids NSAIDs tetrahydropyran derivatives, regarding their antinociceptive effects on acute pain in mice. Male swiss mice were evaluated in the acetic acid\u2010induced abdominal writhing, formalin, tail\u2010flick, open\u2010field, glutamate\u2010 and capsaicin\u2010induced paw licking tests, and in vitro Cox inhibition assay, besides the acute toxicological evaluation. The compounds had an effect on the acetic acid\u2010induced abdominal writhing, formalin (both phases), and tail\u2010flick tests. In the study of the mechanism of action was observed reversion of the antinociceptive effect of the compounds from the previous administration of naloxone, L\u2010NAME (L\u2010nitro\u2010arginine methyl ester), ODQ (1H\u2010[1,2,4]oxadiazolo[4,3\u2010a]quinoxalin\u20101\u2010one), glibenclamide, and nor\u2010binaltorphimine, by the intrathecal and intraperitoneal routes. The prior administration of MK\u2010801 suggests that the modulation of NMDA receptor contributes to the antinociceptive effect of compounds. In summary, hybrid compounds presented central antinociceptive effect, demonstrating participation of the NO\u2010cGMP\u2010K<jats:sup>+<\/jats:sup> ATP pathway, \u03ba\u2010opioid, and NMDA receptors. In addition, the compounds showed inhibition of cyclo\u2010oxygenase enzymes and adverse effects were not observed with dose 300 times greater than the dose used experimentally.<\/jats:p>","DOI":"10.1111\/fcp.12525","type":"journal-article","created":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T13:13:24Z","timestamp":1575551604000},"page":"321-335","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacological evaluation underlying the antinociceptive activity of two new hybrids NSAIDs tetrahydropyran derivatives"],"prefix":"10.1111","volume":"34","author":[{"given":"Poliana de Araujo","family":"Oliveira","sequence":"first","affiliation":[{"name":"Programa Multic\u00eantrico de P\u00f3s\u2010Gradua\u00e7\u00e3o em Ci\u00eancias Fisiol\u00f3gicas Instituto de Ci\u00eancias Biol\u00f3gicas e da Sa\u00fade Universidade Federal Rural do Rio de Janeiro BR465, Km 07 Serop\u00e9dica 23897-000 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