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01-08-2020 | Naloxone | Original Article

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)

Authors: Carina S. Cardoso, Daiany P. B. Silva, Dayane M. Silva, Iziara F. Florentino, James O. Fajemiroye, Lorrane K. S. Moreira, José P. Vasconcelos, Germán Sanz, Boniek G. Vaz, Luciano M. Lião, Danilo da S. Lima, Fernanda Cristina A. dos Santos, Ricardo Menegatti, Elson A. Costa

Published in: Inflammopharmacology | Issue 4/2020

Abstract

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.

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Title: 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)
Authors: Carina S. Cardoso
Daiany P. B. Silva
Dayane M. Silva
Iziara F. Florentino
James O. Fajemiroye
Lorrane K. S. Moreira
José P. Vasconcelos
Germán Sanz
Boniek G. Vaz
Luciano M. Lião
Danilo da S. Lima
Fernanda Cristina A. dos Santos
Ricardo Menegatti
Elson A. Costa
Publication date: 01-08-2020
Publisher: Springer International Publishing
Keywords: Naloxone
Glibenclamide
Opioids
Opioids
Capsaicin
Indomethacin
Published in: Inflammopharmacology / Issue 4/2020
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-020-00685-8

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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)

Abstract

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