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Effects of Naloxone and Flumazenil on Antinociceptive Action of Acetaminophen in Rats

机译:纳洛酮和氟马西尼对大鼠对乙酰氨基酚的镇痛作用

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BACKGROUND: Studies of acetaminophen suggest that multiple nociceptive pathways are involved in the drug's analgesic action.OBJECTIVE: The purpose of this study was to determine whether naloxone and flumazenil were able to modify or antagonize the antinociceptive effect of acetaminophen in rats.METHODS: Adult albino Wistar rats were used in the study and randomly allocated to 1 of 4 groups. The acetaminophen group (A group) was administered IP saline and then 300 mg/kg IP acetaminophen 5 minutes thereafter. The acetaminophen + naloxone group (AN group) was pretreated with 1 mg/kg IP naloxone, followed by 300 mg/kg IP acetaminophen 5 minutes later. The acetaminophen + flumazenil group (AF group) was pretreated with 1 mg/kg IP flumazenil, followed by 300 mg/kg IP acetaminophen 5 minutes later. The control group received 2.5 mL IP saline, followed by an additional 2.5 mL IP injection of saline 5 minutes later. The paw-withdrawal latency period of the rats was assessed by an investigator blinded to treatment using the hot-plate test at 30, 45, 60, and 90 minutes after administration of acetaminophen.RESULTS: Thirty-two rats were evenly randomized by envelope method into 4 groups of 8 rats each. Baseline values for the A, AN, AF, and control groups were not significantly different (9-1 [2.3}, 10.5 [2.7}, 9-8 [3.0}, and 8.9 [1.4} sec, respectively). In the AF group, flumazenil appeared to antagonize the analgesic effect exerted by the acetaminophen in the hot-plate test (30 min, 10.3 [3.7} sec; 45 min, 11.7 [5.1} sec; 60 min, 12.1 [5.1} sec; and 90 min, 12.2 [4.9} sec) and values were not significantly different from those obtained in the control group (30 min, 9-8 [2.2} sec; 45 min, 9-0 [1.6} sec; 60 min, 9.2 [1.6} sec; and 90 min, 8.5 [2.0} sec). In the AN group, naloxone did not significantly affect the values observed in the hot-plate test (30 min, 18.0 [4.5} sec; 45 min, 21.5 [7.8} sec; 60 min, 20.5 [5.9} sec; and 90 min, 22.3 [7.4} sec) and values at all time points were not significantly different from those obtained in theA group (30 min, 17.8 ]7.6] sec; 45 min, 20.9 ]6.9] sec; 60 min, 21.5 {7.3} sec; and 90 min, 23-8 {8.6} sec). All postbaseline values in the A and AN groups were significantly increased versus baseline and versus the control group values (all, P < 0.05). All postbaseline values in the A group were significantly greater than those in the AF group (all, P < 0.05).CONCLUSION: Flumazenil antagonized the analgesic effect exerted by acetaminophen, while naloxone had no significant effect on acetaminophen's antinocicep-tive action in this pain model in rats.
机译:背景:对乙酰氨基酚的研究表明该药物的镇痛作用涉及多种伤害感受途径。目的:本研究的目的是确定纳洛酮和氟马西尼是否能够改变或拮抗对乙酰氨基酚对大鼠的伤害感受作用。 Wistar大鼠用于研究,随机分为4组中的1组。对乙酰氨基酚组(A组)给予IP盐水,然后5分钟后给予300 mg / kg IP对乙酰氨基酚。对乙酰氨基酚+纳洛酮组(AN组)先用1 mg / kg IP纳洛酮预处理,然后在5分钟后用300 mg / kg IP对乙酰氨基酚预处理。对乙酰氨基酚+氟马西尼组(AF组)先用1 mg / kg IP氟马西尼预处理,然后在5分钟后用300 mg / kg IP对乙酰氨基酚进行预处理。对照组接受2.5 mL IP生理盐水,然后在5分钟后再注射2.5 mL IP生理盐水。在对乙酰氨基酚给药后30、45、60和90分钟,使用热板试验不知情的研究人员评估了大鼠的爪缩潜伏期。结果:32只大鼠通过包膜法均匀随机分组分为4组,每组8只大鼠。 A,AN,AF和对照组的基线值没有显着差异(分别为9-1 [2.3},10.5 [2.7},9-8 [3.0}和8.9 [1.4}秒)。在AF组中,氟马西尼似乎拮抗对乙酰氨基酚在热板试验中的镇痛作用(30分钟,10.3 [3.7}秒; 45分钟,11.7 [5.1}秒; 60分钟,12.1 [5.1}秒; 90分钟,12.2 [4.9}秒)和值与对照组相比无显着差异(30分钟9-8 [2.2}秒; 45分钟9-0 [1.6}秒; 60分钟9.2) [1.6}秒; 90分钟,8.5 [2.0}秒)。在AN组中,纳洛酮没有显着影响在热板测试中观察到的值(30分钟,18.0 [4.5}秒; 45分钟,21.5 [7.8}秒; 60分钟,20.5 [5.9}秒和90分钟,22.3 [7.4}秒)和所有时间点的值均与A组(30分钟,17.8 [7.6]秒; 45分钟,20.9 [6.9]秒]; 60分钟,21.5 {7.3}秒;和90分23-8 {8.6}秒)。与基线和对照组相比,A组和AN组的所有基线后值均显着增加(所有,P <0.05)。结论:氟马西尼拮抗对乙酰氨基酚的镇痛作用,而纳洛酮对乙酰氨基酚的止痛作用无明显作用(A组所有基线后值均显着高于AF组(均P <0.05)。大鼠模型。

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