Subcutaneous loperamide prevents gastric lesions induced by necrotizing agents in rats

The effects of subcutaneous loperamide on gastric lesions induced by necrotizing agents were investigated in the rat. Loperamide produced a dose-dependent increase of gastric fluid volume and inhibition of gastric lesions caused by 0.6 N HCl or absolute ethanol. Pretreatment with naloxone almost completely blocked both fluid pooling effect and mucosal protective effect of loperamide. Omeprazole reduced the acidity of the gastric fluid in rats treated with loperamide without significantly decreasing the fluid volume. Various volumes of acid, given orally immediately before 0.6 N HCl, volume-dependently prevented gastric lesions. We conclude that subcutaneous loperamide protects the gastric mucosa against necrotizing agents through luminal dilution of irritants, which is mediated by naloxone-sensitive opiate receptors.