OBSERVATION ON THE IRRITATING ACTION OF FURAPROMIDUM ON MOUSE STOMACH WITH THE EVANS BLUE METHOD AND ITS EFFECTIVE ANTAGONISTS

A method to evaluate the irritating action of furapromidum (F 30066) on mouse stomach is described. Mice receiving oral doses of the drug were immediately given intravenous injection of 1% Evans blue in normal saline and were sacrificed by bleeding 2 hours later. At autopsy, the stomach was everted and the extent of the blue staining on the serous layer of the fundus was assessed visually on an arbitary scale (0-8). It was shown that the degree of blue staining caused by a single dose of furapromidum or xylol correlated well with the severity of the pathological changes of that organ.Eleven drugs were tested for their antagonistic action to the irritating effect of furapromidum on mouse stomach. Drugs were given orally 1 hour before the administration of furaprornidum. It was found that chlorpheniramine, phenergan,diphenhydramine and chlorpromazine were quite active in limiting the extent of blue staining, indomethacin and mefenamic acid showed only moderate effect while atropine exhibited little effect, if at all.When mice were given furapromidum orally in the dosage of 500 mg/kg daily for 10 days, it was found by the Evans blue method that the irritating effect of the drug was reduced gradually with the increasing number of doses. The irritating action of the last dose was only about one-third that of the first. However, if chlorpheniramine was given orally 1 hour before administration of furapromidum during the first 3 days of the course, the irritating effect became evident only on the third day, and in a lcss degree than that of the corresponding group given furapromidum alone, and it gradually disappeared as the treatment was continued. These results correlated basically with the gross and microscopic pathological alterations of the stomach. The antischistosomal effect of furapromidum was practically not affected by chlorpheniramine.