Evaluation of the anti-ulcerogenic activity of the antidepressants duloxetine, amitriptyline, fluoxetine and mirtazapine in different models of experimental gastric ulcer in rats.
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).
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China. jichengxue@imm.ac.cn
Cheng-Xue
CX
Ji
Dong-Sheng
DS
Fan
Wei
W
Li
Liang
L
Guo
Zi-Liang
ZL
Liang
Rui-Ming
RM
Xu
Jian-Jun
JJ
Zhang
D000639:Amitriptyline / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D000068736:Duloxetine Hydrochloride; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use; D007101:Immersion / Q000009:adverse effects; D007213:Indomethacin / Q000009:adverse effects; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000078785:Mirtazapine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000009:adverse effects; D012149:Restraint, Physical / Q000009:adverse effects; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology; D013315:Stress, Psychological / Q000150:complications; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use; D014867:Water
D000897:Anti-Ulcer Agents; D000928:Antidepressive Agents; D013876:Thiophenes; D005473:Fluoxetine; D014867:Water; D000639:Amitriptyline; D008803:Mianserin; D012110:Reserpine; D000068736:Duloxetine Hydrochloride; D000078785:Mirtazapine; D007213:Indomethacin