Structural characteristics of histamine H2 receptor antagonists that scavenge hypochlorous acid

Gastric and duodenal ulcers are characterized by hypersecretion of gastric acid and pepsin, inflammation of the mucosa and an influx of neutrophils. These cells can produce reactive oxygen species after stimulation. Particularly hydroxyl radicals and hypochlorous acid (HOCl) can be cytotoxic and damage the gastroduodenal mucosa. It has been shown that histamine H2 receptor antagonists such as cimetidine, ranitidine and famotidine are good hydroxyl radical scavengers. This study was undertaken to investigate whether these agents were able to scavenge the cytotoxic HOCl, and if so, which part of the molecule could be responsible for this action. It appears that the sulfur atom in the compound is of importance for scavenging HOCl. This finding should be taken into consideration in the development of new anti ulcer drugs, as HOCl is a detrimental factor in the pathophysiology of gastroduodenal ulcers.