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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Research Article

Antinociceptive Effects of Aza-Bicyclic Isoxazoline-Acylhydrazone Derivatives in Different Models of Nociception in Mice

Author(s): Fernanda Virginia Barreto Mota, Felipe Neves Coutinho, Vanessa Mylenna Florêncio de Carvalho, Julyanne Cunha de Assis Correia, Isla Vanessa Gomes Alves Bastos, Pedro Paulo Marcelino-Neto, Rafael Matos Ximenes, Dalci José Brondani, Antônio Rodolfo de Faria, Pascal Marchand and Teresinha Gonçalves da Silva*

Volume 22, Issue 4, 2022

Published on: 31 January, 2022

Page: [247 - 258] Pages: 12

DOI: 10.2174/1568026622666220105102508

Price: $65

Abstract

Background: In a study recently published by our research group, the isoxazoline-acylhydrazone derivatives R-99 and R-123 presented promising antinociceptive activity. However, the mechanism of action of this compound is still unknown.

Objective: This study aimed to assess the mechanisms involved in the antinociceptive activity of these compounds in chemical models of pain.

Methods: Animals were orally pretreated and evaluated in the acetic acid-, formalin-, capsaicin-, carrageenan- and Complete Freund's Adjuvant (CFA)-induced pain models in mice. The effects of the compounds after pretreatment with naloxone, prazosin, yohimbine, atropine, L-arginine, or glibenclamide were studied, using the acetic acid-induced writhing test to verify the possible involvement of opioid, α1-adrenergic, α2-adrenergic or cholinergic receptors, and nitric oxide or potassium channels pathways, respectively.

Results: R-99 and R-123 compounds showed significant antinociceptive activity on pain models induced by acetic acid, formalin, and capsaicin. Both compounds decreased the mechanical hyperalgesia induced by carrageenan or CFA in mice. The antinociceptive effects of R-99 and R-123 on the acetic acid-induced writhing test were significantly attenuated by pretreatment with naloxone, yohimbine or atropine. R-99 also showed an attenuated response after pretreatment with atropine and glibenclamide. However, on the pretreatment with prazosin, there was no change in the animals' response to both compounds.

Conclusion: R-99 and R-123 showed antinociceptive effects related to mechanisms that involve, at least in part, interaction with the opioid and adrenergic systems and TRPV1 pathways. The compound R-99 also interacts with the cholinergic pathways and potassium channels.

Keywords: Pain, Receptors, Hyperalgesia, Opioid, Adrenergic system, Potassium channels.

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