Involvement of the NO/cGMP/KATP pathway in the antinociceptive effect of the new pyrazole 5-(1-(3-fluorophenyl)-1H-pyrazol-4-yl)-2H-tetrazole (LQFM-021)

AbstractThe pyrazol compounds are known to possess antipyretic, analgesic and anti-inflammatory activities. This study was conducted to investigate the peripheral antinociceptive effect of the pyrazole compound 5-(1-(3-Fluorophenyl)-1H-pyrazol-4-yl)-2H-tetrazole (LQFM-021) and involvement of opioid receptors and of the NO/cGMP/KATP pathway. The oral treatments in mice with LQFM-021 (17, 75 or 300 mg/kg) decreased the number of writhing. In the formalin test, the treatments with LQFM-021 at doses of 15, 30 and 60 mg/kg reduced the licking time at both neurogenic and inflammatory phases of this test. The treatment of the animals with LQFM-021 (30 mg/kg) did not have antinociceptive effects in the tail-flick and hot plate tests. Furthermore, pre-treatment with naloxone (3 mg/kg i.p.), L-name (10 mg/kg i.p.), ODQ (10 mg/kg i.p.) or glibenclamide (3 mg/kg i.p.) antagonized the antinociceptive effect of LQFM-021 in both phases of the formalin test. In addition, it was also demonstrated that the treatments of mice with LQFM-021(15, 30 and 60 mg/kg) did not compromise the motor activity of the animals in the chimney test. Only the highest dose used in the antinociceptive study promoted changes in the open field test and pentobarbital-induced sleep test, thus ruling out possible false positive effects on nociception tests. Our data suggest that the peripheral antinociception effects of the LQFM-021 were mediated through the peripheral opioid receptors with activation of the NO/cGMP/KATP pathway