To make an experimental model of the duodenal ulcer is necessary to investigate the mechanism of the duodenal ulcer and the efficacy of the drugs for the duodenal ulcer.
The author tried an experimental study of mepirizole?induced duodenal ulcer. 1viepirizole ((1?( 4?methoxy?6 ?methyl -2 ?pyrimidinyl ) ? 3?methyl -5?rnethoxy pyrazole)) is a sort of an antiinf lammatory drugs Various doses of mcpirizole(50, 100, 200, and 300w/kg) were administered or-ally as a single dose to rats, and then changes of the morphology of the stomach and duodenum and the gastric acidity were observed.
1. Morphologic changes
On gross examination of the stomach and duodenum of the rats that we-re fasted for 24 hours after various amount of mepirizole administration, mepirizole?induced ulcer was confined to the duodenum, and the gastric mucosa was only erosive but not ulcerative.
The size of duodenal ulcer was proportional to the administered dose of mepirizole. In 200 and 300sq/kg of mepirizole administcred groups, all animals showed duodenal ulcer. And perforation rate of duodenal ulcer were 25 % and 75 %, respectively. But the mortality rate was relatively low (5 % in 200 sq/kg- groups, and 10 % in 300 sag/kg? group).
Histologically, necrotic lesions were confined to the duodenal mucosa in 50 and 100w/4? groups, but in 200 and 300 Irv/kg? groups, most of experimental animals showed duodenal ulcer which penetrated musculoserosal layer. Desquamation and necrosis of the gastric mucosal cells were noted in groups of large doses of mepirizole (more than 100 xg/kg ). 2. Gastric acidity
An increase of gastric acidity was dependent to the dosage and the time interval of n:epi rizole treatment.
According to these results, mepirizole is an excellent agent for an experimental duodenal ulcer and the effective dose is about 200 ag/kg. Nothing per oral for 24 hours after mepirizole administration is mandat - ory. Increased gastric acidity might be a major role in the mechanisms of mepirizole?induced duodenal ulcer.
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