Evaluation of the systemic and spinal antinociceptive effect of a new hybrid NSAID tetrahydropyran derivative

Autor: Roberto Laureano-Melo, Vivian de Assunção Nogueira Carvalho, Gabriela Mastrangelo Gonçalves, Thayane Ferreira da Costa Fernandes, Bruno Guimarães Marinho, Saulo Luis Capim, Joyce Mattos de Oliveira, Mário L. A. A. Vasconcellos, Gabriela de Carvalho Cid, Wellington da Silva Côrtes
Rok vydání: 2021
Předmět:
Zdroj: Clinical and Experimental Pharmacology and Physiology. 49:419-431
ISSN: 1440-1681
0305-1870
DOI: 10.1111/1440-1681.13617
Popis: Pain is responsible for inducing physical and mental stress, interfering negatively in patients' quality of life. Classic analgesic drugs, such as opioids and non-steroidal anti-inflammatory drugs, are known for their wide range of adverse effects, making it important to develop new drugs. Thus, this study aimed to analyze the action of the hybrid compound cis- (±) -acetate of 4-chloro-6- (naphthalene-1-yl) -tetrahydro-2h-pyran -2-yl) methyl2- (2- (2,6-dichlorophenylamine) phenyl (LS19) under acute nociceptive conditions, and deepened the understanding of the responsible mechanisms. Male swiss mice were evaluated in the acetic acid-induced abdominal writhing, formalin, tail-flick, capsaicin- and glutamate-induced nociception, thermal stimulation in animals injected with capsaicin and rotarod tests besides the acute and subchronic toxicological evaluation. The compound showed effect on the acetic acid-induced abdominal writhing, formalin (both phases), tail-flick, thermal stimulation in animals injected with capsaicin and capsaicin-induced nociception tests. In the study of the mechanism of action was observed reversion of the antihyperalgesic effect of the compound from the previous intraperitoneal and intrathecal administration of naloxone, nor-binaltorphimine, naltrindole, methylnaltrexone, 7-nitroindazole, L-NAME, ODQ, glibenclamide on the tail flick test. In the thermal stimulation in animals injected with capsaicin, the compound showed antinociceptive effect by oral and intraplantar routes, besides to reducing the levels of TNF-α, IL-1β and PGE2 in the paws previously administered with capsaicin. There were no signs of acute and subchronic intoxication with the compound. In summary, the compound LS19 presented spinal and local antihyperalgesic effect, demonstrating participation of the opioid/NO/cGMP/K+ ATP pathway and TRPV1 receptors and it demonstrated safety in its use in mice.
Databáze: OpenAIRE
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