Evaluation of the anti-ulcerogenic activity of the antidepressants duloxetine, amitriptyline, fluoxetine and mirtazapine in different models of experimental gastric ulcer in rats

Abstract

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 20mg/kg, i.p.), amitriptyline (10 and 20mg/kg, i.p.), mirtazapine (10 and 20mg/kg, i.p.) and fluoxetine (5 and 10mg/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 (20mg/kg, i.p.), amitriptyline (10 and 20mg/kg, i.p.), fluoxetine (10 and 20mg/kg, i.p.) and mirtazapine (5, 10 and 20mg/kg, i.p.) significantly decreased indomethacin (30mg/kg, i.p.)-induced gastric lesions and intraluminal bleeding. In reserpine (25mg/kg, i.p.)-induced gastric ulcer experiment, duloxetine (5, 10 and 20mg/kg, i.p.), amitriptyline (5, 10 and 20mg/kg, i.p.), fluoxetine (10mg/kg, i.p.) and mirtazapine (5mg/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).