Florentino Iziara F, Galdino Pablinny M, De Oliveira Lanussy P, Silva Daiany P B, Pazini Francine, Vanderlinde Frederico A, Lião Luciano M, Menegatti Ricardo, Costa Elson A
Institute of Biological Sciences, Department of Pharmacology, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil.
Institute of Biological Sciences, Department of Pharmacology, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil.
Nitric Oxide. 2015 May 1;47:17-24. doi: 10.1016/j.niox.2015.02.146. Epub 2015 Mar 6.
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.
已知吡唑化合物具有解热、镇痛和抗炎活性。本研究旨在探讨吡唑化合物5-(1-(3-氟苯基)-1H-吡唑-4-基)-2H-四氮唑(LQFM-021)的外周抗伤害感受作用以及阿片受体和NO/cGMP/K(ATP)途径的参与情况。用LQFM-021(17、75或300mg/kg)对小鼠进行口服治疗可减少扭体次数。在福尔马林试验中，15、30和60mg/kg剂量的LQFM-021治疗可减少该试验神经源性和炎症期的舔舐时间。用LQFM-021(30mg/kg)对动物进行治疗在甩尾试验和热板试验中没有抗伤害感受作用。此外，用纳洛酮(3mg/kg腹腔注射)、L-精氨酸甲酯(10mg/kg腹腔注射)、ODQ(10mg/kg腹腔注射)或格列本脲(3mg/kg腹腔注射)进行预处理可拮抗LQFM-021在福尔马林试验两个阶段的抗伤害感受作用。此外，还证明用LQFM-021(15、30和60mg/kg)对小鼠进行治疗不会损害动物在烟囱试验中的运动活性。只有抗伤害感受研究中使用的最高剂量在旷场试验和戊巴比妥诱导的睡眠试验中引起了变化，从而排除了对伤害感受试验可能的假阳性影响。我们的数据表明，LQFM-021的外周抗伤害感受作用是通过外周阿片受体介导的，激活了NO/cGMP/KATP途径。
