Gastroprotective effect of MX1 (a novel salt of the active metabolite of roxatidine with a complex of bismuth and citric acid) against stress ulcers in rats.

We have studied the effect of the newly synthesized agent MX1, a salt of the active metabolite of the H2-blocker roxatidine with a complex of bismuth and citric acid (N-[3-(3-(1-piperidinylmethyl)phenoxy)propyl]-hydroxyacetamide+ ++ -2-hydroxypropane-1,2,3-tricarboxilate-bismuth(3+) complex), against restraint stress ulcers in rats (24 h immobilization). The effects of MX1 (12.5, 50, 125, 184 and 250 mg kg-1) were compared with the effects of equimolar doses of roxatidine (6.5, 25, 70, 100 and 140 mg kg-1) and bismuth subcitrate (6.5, 25, 70, 100 and 140 mg kg-1). The results show that MX1-pre-treatment, at all the doses used, significantly reduces the mean number and size of ulcers. Even at the lowest dose the number of ulcers was reduced by 64.3% and the size of the ulcer by 55.9%. Roxatidine (25, 70, 100 and 140 mg kg-1) dose-dependently reduces ulcer size and number by 24.6, 55.6, 85.3 and 89.0% and by (+7.2), 14.3, 57.1 and 67.9%, respectively. Bismuth subcitrate significantly reduces ulcer size and number only at the highest dose employed (-28.5 and -44.8%, respectively). The morphometric results have been confirmed histomorphologically. The results suggest that MX1 has a gastroprotective effect against stress-induced ulcers which is similar to that of the parent compound and more pronounced than that of bismuth subcitrate.