Title:Antinociceptive Effects of Aza-Bicyclic Isoxazoline-Acylhydrazone Derivatives
in Different Models of Nociception in Mice
Volume: 22
Issue: 4
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*
Affiliation:
- Department of Antibiotics, Federal University of Pernambuco (UFPE), Recife-PE, Brazil
Keywords:
Pain, Receptors, Hyperalgesia, Opioid, Adrenergic system, Potassium channels.
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.