H2-antagonist inhibition of human neutrophil superoxide anion synthesis

In the mmol/L concentration range, cimetidine and ranitidine suppress superoxide anion generation by isolated intact human neutrophils. However, at normal pharmacologic concentrations in the mumol/L range, even prolonged exposure of neutrophils to these agents has no demonstrable effect on toxic oxygen species synthesis. In vitro inhibition does not involve neutrophil activation-densensitization or neutrophil cytotoxicity and is reversible to a great extent by drug washout. In the examination of possible free-radical scavenging action of these drugs, it was demonstrated that both drugs inhibit superoxide anion production by xanthine oxidase but not by chelated iron. This raises the possibility that these agents may bear structural similarities to oxypyrazolopyrimidines such as allopurinol.