Effect of a new potent H2-blocker, 3-]]]2-[(diaminomethylene)amino]-4-thiazolyl]methyl]-thio]-N2-sulfamoylpropionamidine (YM-11170) on gastric secretion induced by histamine and food in conscious dogs.

The inhibitory effect of a new H2-receptor antagonist YM-11170 on gastric acid response to histamine and food was compared with that of cimetidine in the conscious dog with a Heidenhain pouch. When given intravenously at a steady state of gastric secretion by continuous infusion of histamine. YM-11170 was 42 times more potent and 1.3 times longer-lasting (p less than 0.05) than cimetidine in reducing the total acid output. The higher potency of YM-11170 than that of cimetidine was also demonstrated in oral antisecretory tests with histamine. The oral ED50 relative to i.v. ED50 as an indirect indication of absorption rate of the drugs was 2.9 for YM-11170 and 2.7 for cimetidine. The secretory response to food stimulation was also antagonized by oral administration of YM-11170 with 40 times greater potency than that of cimetidine. The antisecretory effects of the drugs on the histamine-induced gastric secretion were characterized by a marked decrease in the secretory volume. No behavioral change was observed in association with the H2-blockers. These results indicate that YM-11170 is a very potent inhibitor of gastric acid secretion and also suggest that the absorption rate of YM-11170 from the gastro-intestinal tract is similar to that of cimetidine.