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).
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.
['Cardoso|Carina S|CS|', 'Silva|Daiany P B|DPB|', 'Silva|Dayane M|DM|', 'Florentino|Iziara F|IF|', 'Fajemiroye|James O|JO|', 'Moreira|Lorrane K S|LKS|', 'Vasconcelos|José P|JP|', 'Sanz|Germán|G|', 'Vaz|Boniek G|BG|', 'Lião|Luciano M|LM|', 'Lima|Danilo da S|DDS|', 'Dos Santos|Fernanda Cristina A|FCA|', 'Menegatti|Ricardo|R|', 'Costa|Elson A|EA|http://orcid.org/0000-0003-1996-0901']
D000700:Analgesics D000818:Animals D000893:Anti-Inflammatory Agents D002351:Carrageenan D002465:Cell Movement D015232:Dinoprostone D004487:Edema D005260:Female D006930:Hyperalgesia D007962:Leukocytes D051379:Mice D059225:Nociception D010147:Pain Measurement D010998:Pleurisy D013777:Tetrazoles D014230:Triazoles
ASICs TRPV1 TNF-α Inflammation Opioid receptors Pain