Evaluation of the anti-ulcerogenic activity of the antidepressants duloxetine, amitriptyline, fluoxetine and mirtazapine in different models of experimental gastric ulcer in rats
Evaluation of the anti-ulcerogenic activity of the antidepressants duloxetine, amitriptyline, fluoxetine and mirtazapine in different models of experimental gastric ulcer in rats
复制标题
抗抑郁药度洛西汀、阿米替林、氟西汀和米氮平在不同大鼠实验性胃溃疡模型中的抗溃疡活性评价
DOI：
10.1016/j.ejphar.2012.06.041
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发表时间：
2012-09-15
影响因子：
5
通讯作者：
Zhang, Jian-Jun
中科院分区：
文献类型：
--
作者：
Ji, Cheng-Xue;Fan, Dong-Sheng;Zhang, Jian-Jun
在大鼠胃溃疡模型上，比较了度洛沙坦、阿米替林、米氮平和氟西汀急性全身给药的效果。与溶剂对照组相比，度洛沙汀（5、10和20 mg/kg，i. p.），阿米替林（10和20 mg/kg，i. p.），米氮平（10和20 mg/kg，i. p.）和氟西汀（5和10 mg/kg，i. p.）显著防止水浸加束缚应激诱导的胃损伤，如溃疡指数和管腔内出血评分的剂量依赖性降低所证明的。度洛沙汀（20 mg/kg，i. p.），阿米替林（10和20 mg/kg，i. p.），氟西汀（10和20 mg/kg，i. p.）和米氮平（5、10和20 mg/kg，i. p.）显著降低吲哚美辛（30 mg/kg，i. p.）诱发胃损伤和腔内出血。利血平（25 mg/kg，i. p.）诱导胃溃疡实验，度洛沙汀（5、10和20 mg/kg，i. p.），阿米替林（5、10和20 mg/kg，i. p.），氟西汀（10 mg/kg，i. p.）和米氮平（5 mg/kg，i. p.）显著减轻胃损伤和腔内出血。这些结果（a）强调了不同抗抑郁药类别的药物在各种动物胃溃疡模型中的相关抗溃疡作用的关系，（B）表明不同影响去甲肾上腺素和5-羟色胺水平的抗抑郁药（如度洛西汀，阿米替林和米氮平）在各种胃溃疡动物模型中的抗溃疡作用比仅影响5-羟色胺水平的药物更强和有效（如氟西汀）。(C)2012爱思唯尔有限公司版权所有。
The effects of acute systemic administration of duloxetine, amitriptyline, mirtazapine and fluoxetine were compared in experimental models of gastric ulcer in rats. Compared with the vehicle control group, duloxetine (5, 10 and 20 mg/kg, i.p.), amitriptyline (10 and 20 mg/kg, i.p.), mirtazapine (10 and 20 mg/kg, i.p.) and fluoxetine (5 and 10 mg/kg, i.p.) significantly protected against water-immersion plus restraint stress-induced gastric lesions, as evidenced by dose-dependent decrease in ulcer index and score for intraluminal bleeding. Duloxetine (20 mg/kg, i.p.), amitriptyline (10 and 20 mg/kg, i.p.), fluoxetine (10 and 20 mg/kg, i.p.) and mirtazapine (5, 10 and 20 mg/kg, i.p.) significantly decreased indomethacin (30 mg/kg, i.p.)-induced gastric lesions and intraluminal bleeding. In reserpine (25 mg/kg, i.p.)-induced gastric ulcer experiment, duloxetine (5, 10 and 20 mg/kg, i.p.), amitriptyline (5, 10 and 20 mg/kg, i.p.), fluoxetine (10 mg/kg, i.p.) and mirtazapine (5 mg/kg, i.p.) significantly attenuated gastric lesions and intraluminal bleeding. These results (a) highlighted the relationship in correlating antiulcer effect of drugs from different antidepressant classes across various animal gastric ulcer models and (b) suggested that antidepressants that differently affected both norepinephrine and serotonin levels (such as duloxetine, amitriptyline and mirtazapine) had more potent and efficacious antiulcer effect in various gastric ulcer animal models than drugs that only affected serotonin level (such as fluoxetine). (C) 2012 Elsevier B.V. All rights reserved.