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.
Marazova
K
K
Department of Pharmacology and Toxicology, Medical Faculty of Sofia, Bulgaria.
Klouchek
E
E
Popov
A
A
Ivanov
C H
CH
Krushkov
I
I
D000818:Animals; D000863:Antacids / Q000627:therapeutic use*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D004338:Drug Combinations; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D008297:Male; D009942:Organometallic Compounds / Q000627:therapeutic use*; D010437:Peptic Ulcer / Q000209:etiology / Q000517:prevention & control*; D010880:Piperidines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical
D000863:Antacids; D000897:Anti-Ulcer Agents; D004338:Drug Combinations; D006635:Histamine H2 Antagonists; C108695:MX(1) complex; D009942:Organometallic Compounds; D010880:Piperidines; C002791:bismuth tripotassium dicitrate; C053742:roxatidine acetate