title: 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).
abstract: The 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/K(ATP) 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.
authors.affiliation: Institute of Biological Sciences, Department of Pharmacology, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil. Electronic address: Iziara_bia@hotmail.com.
authors.forename: Iziara F
authors.initials: IF
authors.lastname: Florentino
authors.affiliation: Institute of Biological Sciences, Department of Pharmacology, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil.
authors.forename: Pablinny M
authors.initials: PM
authors.lastname: Galdino
authors.affiliation: Institute of Biological Sciences, Department of Pharmacology, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil.
authors.forename: Lanussy P
authors.initials: LP
authors.lastname: De Oliveira
authors.affiliation: Institute of Biological Sciences, Department of Pharmacology, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil.
authors.forename: Daiany P B
authors.initials: DP
authors.lastname: Silva
authors.affiliation: Faculty of Pharmacy, Laboratory of Medicinal Pharmaceutical Chemistry, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Francine
authors.initials: F
authors.lastname: Pazini
authors.affiliation: Institute of Biological Sciences, Department of Physiological Sciences, Federal Rural University of Rio de Janeiro, Seropédica, RJ, Brazil.
authors.forename: Frederico A
authors.initials: FA
authors.lastname: Vanderlinde
authors.affiliation: Chemistry Institute, Federal University of Goias, Campus Samambaia, Goiânia, GO, Brazil.
authors.forename: Luciano M
authors.initials: LM
authors.lastname: Lião
authors.affiliation: Faculty of Pharmacy, Laboratory of Medicinal Pharmaceutical Chemistry, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Menegatti
authors.affiliation: Institute of Biological Sciences, Department of Pharmacology, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil.
authors.forename: Elson A
authors.initials: EA
authors.lastname: Costa
mesh_terms: D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000378:metabolism; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: C585652:5-(1-(3-fluorophenyl)-1H-pyrazol-4-yl)-2H-tetrazole; D000700:Analgesics; D054086:KATP Channels; D011720:Pyrazoles; D011957:Receptors, Opioid; D013777:Tetrazoles; D009569:Nitric Oxide; D006152:Cyclic GMP
keywords: LQFM-021; Nitric oxide; Peripheral antinociception; Pyrazole derivative