H-2-RECEPTOR ANTAGONISTS ARE SCAVENGERS OF OXYGEN RADICALS

Potential oxygen radical scavenging properties of the Hz-receptor anta gonists cimetidine, ranitidine and famotidine were investigated. These drugs, although ineffective against superoxide anion and hydrogen per oxide, can scavenge hydroxyl radical (OH.) with a very high rate const ant, which is about tenfold higher than that of the specific scavenger mannitol for famotidine (1.7 x 10(10) mol(-1) s(-1)) and cimetidine ( l.6 x 10(10) mol(-1) s(-1)), ranitidine displaying a rate constant of 7.5 x 10(9) mol(-1) s(-1). These OH. scavenging effects are significan t beginning from 10, 28 and 100 mu mol l(-1) concentration for famotid ine, cimetidine and ranitidine, respectively, thus suggesting that the drugs may effectively act as OH scavengers in vivo especially in the gastric lumen. Only cimetidine can apparently bind and inactivate iron , which further emphasizes its antioxidant capacity. Moreover, all dru gs, even at 10 mu mol l(-1) concentration, show powerful scavenging ef fects on hypochlorous acid and monochloramine, which are cytotoxic oxi dants arising from inflammatory cells, such as neutrophils. These data suggest that some therapeutical effects of H-2-receptor antagonists i n peptic ulcer may also be related to their antiradical-antioxidant ca pacity, and that these drugs could potentially be used in other diseas e entities characterized by free radical-mediated oxidative stress in vivo.