Mechanisms involved in the antinociceptive and anti-inflammatory effects of a new triazole derivative: 5-[1-(4-fluorophenyl)-1H-1,2,3-triazol-4-yl]-1H-tetrazole (LQFM-096)

Cardoso, Carina Sofia; Silva, Daiany Priscilla Bueno da; Silva, Dayane Moreira da; Florentino, Iziara Ferreira; Fajemiroye, James Oluwagbamigbe; Moreira, Lorrane Kelle da Silva; Vasconcelos, Jose Pacifico de; Sanz Lobón, Germán; Vaz, Boniek Gontijo; Liao, Luciano Morais; Santos, Fernanda Cristina Alcantara dos; Menegatti, Ricardo; Costa, Elson Alves

Mechanisms involved in the antinociceptive and anti-inflammatory effects of a new triazole derivative: 5-[1-(4-fluorophenyl)-1H-1,2,3-triazol-4-yl]-1H-tetrazole (LQFM-096)

Data

2020

Autores

Cardoso, Carina Sofia

Silva, Daiany Priscilla Bueno da

Silva, Dayane Moreira da

Florentino, Iziara Ferreira

Fajemiroye, James Oluwagbamigbe

Moreira, Lorrane Kelle da Silva

Vasconcelos, Jose Pacifico de

Sanz Lobón, Germán

Vaz, Boniek Gontijo

Liao, Luciano Morais

Resumo

The aim of this study was to design, synthesize and evaluate the potential analgesic and anti-inflammatory effects of 5-[1-(4-fluorphenyl)-1H-1,2,3-triazol-4-yl]-1H-tetrazole—(LQFM-096: a new triazole compound) as well as to elucidate its possible mechanisms of action. The oral administration of LQFM-096 (10, 20 or 40 mg/kg) decreased the number of writhing in mice. At the dose of 20 mg/kg, LQFM-096 reduced the licking time at both neurogenic and inflammatory phases of the formalin test. Pretreatment with naloxone (3 mg/kg) and glibenclamide (3 mg/kg) attenuated the antinociceptive effect of LQFM-096 in the first phase of the formalin test. At the dose of 20 mg/kg, LQFM-096 also decreased the licking time in the acidified saline-induced and capsaicin-induced nociception. This effect was blocked by naloxone (3 mg/kg) pretreatment prior to the administration of LQFM-096. In addition, LQFM-096 inhibited hyperalgesia induced by carrageenan and PGE2. Naloxone (3 mg/kg) attenuated the effect of LQFM-096 through disinhibition of PGE2-induced hyperalgesia. The anti-inflammatory effect of LQFM-096 was demonstrated in carrageenan-induced oedema or pleurisy as well as CFA-induced arthritis. The hyperalgesia and cellular migration in CFA-induced arthritis were reduced significantly. Altogether, these findings suggest antinociceptive effect of LQFM-096 and implicate the modulation of ASICs/TRPV1 channels by opioid/KATP pathway. The anti-inflammatory effect of LQFM-096 was mediated by a reduction in oedema, leukocytes migration, TNF-α, PGE2 levels and myeloperoxidase activity.

Palavras-chave

Pain, Inflammation, Opioid receptors, ASICs, TRPV1, TNF-α

Citação

CARDOSO, Carina S. et al Mechanisms involved in the antinociceptive and anti-inflammatory effects of a new triazole derivative: 5-[1-(4-fluorophenyl)-1H-1,2,3-triazol-4-yl]-1H-tetrazole (LQFM-096). Inflammopharmacology, London, v. 28, p. 877-892, 2020. DOI: 10.1007/s10787-020-00685-8. Disponível em: https://link.springer.com/article/10.1007/s10787-020-00685-8. Acesso em: 28 jun. 2023.