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Effects of irsogladine maleate (IM), in combination with histamine H2-receptor antagonists or a muscarinic receptor antagonist, on the formation of stress ulcer were investigated in rats. The ED50 of IM and that of cimetidine for suppressing stress ulceration were remarkably reduced when these drugs were used in combination. ED50s in this case were less than the theoretical values calculated on the basis of additive action, thereby suggesting the synergistic effect of IM and cimetidine. The synergistic effect of IM and ranitidine or famotidine in suppressing stress ulceration was also observed, while IM and pirenzepine did not always produce a synergistic effect. In addition, for acetic acid-induced gastric ulcers, combined administration of IM and cimetidine also markedly potentiated ulcer healing. The marked synergistic potentiation of IM and histamine H2-receptor antagonists may be due to compensatory coordination of both drugs on the gastric secretion and mucosal microcirculation. These results suggest that the combination of IM and histamine H2-receptor antagonists may be beneficial in clinical gastric ulcer therapy.

Synergistic effect of irsogladine maleate and histamine H2-receptor antagonists on experimental gastric ulcers in rats.