RP-73870, A GASTRIN CHOLECYSTOKININ-B RECEPTOR ANTAGONIST WITH POTENTANTIULCER ACTIVITY IN THE RAT/

RP 73870, the racemic potassium salt of -methyl]-3-ureido}-3-phenyl}-2 -ethylsulfonate-(RS) is a potent, reversible antagonist of both gastri n and cholecystokinin-B receptors in guinea pig and rat tissues. This compound is a potent inhibitor of pentagastrin-stimulated gastric acid secretion in the perfused rat stomach. RP 73870 also inhibits basal g astric acid secretion in the rat, although at doses higher than that r equired for inhibition of pentagastrin-stimulated gastric acid secreti on. RP 73870 is a potent inhibitor of aspirin-induced gastric damage i n the rat. In the prevention of aspirin-induced gastric damage, RP 738 70, given p.o., was 10-fold less potent than when given i.v. RP 73870 was as potent as a H-2 receptor antagonist or proton pump inhibitor in the prevention of cysteamine-induced duodenal ulcers in the rat. Rela tive to other gastrin/cholecystokinin-B antagonists, RP 73870 demonstr ates greater affinity to gastrin binding sites, and possesses a unique spectrum of in vivo biological activities appropriate for an anti-ulc er indication.