Effect of Single and Repeated Administration of Amitriptyline on Experimental Gastric Ulcer

Abstract

Amitriptyline is an antidepressant drug widely used as analgesic in the management of chronic pain syndromes. It is also attracting the attention of researchers as an alternative agent for peptic ulcer management because studies have shown that most patients with peptic ulcer also suffer from depression. Thus, this study was conducted to investigate gastroprotective effects of single and repeated dose administration of amitriptyline against indomethacin-induced gastric injury in rats. Rats were randomly divided into three groups of eight rats/each. For 14 days, Group I (control) and Group II (single dose) received distilled water; Group III (repeated dose) received 10 mg/kg amitriptyline orally once daily. On day 15, Group I was given distilled water; Group II and III were given 10 mg/kg amitriptyline orally. Thirty minutes later, indomethacin (25 mg/kg) was administrated orally to all the groups. Six hours after indomethacin administration, animals were sacrificed under thiopental sodium anaesthesia, stomachs were rapidly removed, cut along the greater curvature and cleaned. The stomachs were macroscopically evaluated; total area of stomach and visible ulcerated areas were measured using millimeter square paper. Finally, the stomachs were fixed in 10% formalin for histopathologic  valuation. Single dose administration of amitriptyline significantly reduced ulcer indexes and gastric erosions as compared to the control group.
However, its role against inflammatory reactions such as necrosis, polymorphonuclear leucocyte infiltration, neutrophil and eosinophil reactions were statistically insignificant. On the other hand, repeated dose administration of amitriptilyine produced significant gastroprotective effects as observed from macroscopical and histopathological evaluation results. Moreover, there was also a significant difference in the gastroprotective effects between single and repeated dose of amitriptyline against indomethacin-induced gastric damage. In conclusion, the results of this study  evealed that repeated dose administration of amitriptyline showed better gastroprotective effects compared to single dose amitriptyline administration and the control group.

Keywords: amitriptyline, gastroprotective effects, indomethacin, histopathologic evaluation, rats