Effects of (-)-cis-2, 3-Dihydro-3-(4-methylpiperazinylmethyl)-2-phenyl-1, 5-benzothiazepin-4-(5H)-one Hydrochloride (BTM-1086) on Ulceration, Gastic Secretion and Mucosal Blood Flow in Experimental Animals

Anti-ulcerous and anti-secretory effects of (-)-cis-2, 3-dihydro-3-(4-methylpiperazinylmethyl)-2-phenyl-1, 5-benzothiazepin-4-(5H)-one hydrochloride (BTM-1086), a new peptic-ulcer therapeutic agent, were studied in rats. BTM-1086 effectively prevented the ulceration of pylorus-ligated rats. A remarkable inhibition of gastric secretion was found at a dose of 0.1 mg/kg s.c. within a short period (6 h) after pylorus ligation. In the stomach-perfused rats, BTM-1086 (0.02 to 0.04 mg/kg i.v.) distinctly inhibited the teragastrin- and carbachol-induced gastric acid secretion, but only weakly inhibited the histamine-induced secretion. BTM-1086 also had a depressive effect on the gastric secretion stimulated by such secretagogues as tetragastrin, carbachol and histamine in rats with acute gastric fistulae. BTM-1086 increased the gastric mucosal blood flow in normal and indomethacin-induced ischemic rats. It also increased the gastric mucosal blood flow in water-immersion stress mcie at a dose equivalent to that used to prevent the development of ulcers.These results suggest that the antiulcer effects of BTM-1086 are mainly due to the inhibition of gastric acid secretion and to the increase of gastric mucosal blood flow.