Abstract

Two hours following the subcutaneous injection of 10.0 mg/kg Polymyxin B, a histamine liberator, 90% of the rats tested had gastric hemorrhages. Epinephrine was the most effective agent tested for prevention of the gastric lesions. Antihistaminics such as cyproheptadine, chlorpheniramine and pyrilamine were also active. Chlorpromazine and Dibenzyline were active but required high doses to provide protection. Anticholinergic drugs and an antacid were not effective against the Polymyxin B lesions. The pharmacological data, combined with experiments on the effect of Polymyxin B on gastric secretion, indicated that the production of lesions was due to gastric vascular changes with no involvement of the gastric secretory mechanism. The data also suggest that drug antagonism of Polymyxin B gastric lesions can be ascribed to a general effect of the drugs on the cardiovascular action of released histamine rather than to the direct antagonistic effect on the gastric vasculature.