GASTRIC ANTISECRETORY AND OTHER PHARMACOLOGIC STUDIES OF 3-METHYLAMINO-2,1-BENZISOTHIAZOLE

¹ Research Laboratories, Parke, Davis & Company, Ann Arbor, Michigan

3-Methylamino-2,1-benzisothiazole (CI-624) and its HC1 salt (CI-624 HC1) were studied in rats and dogs for their effects on gastric secretion and other biologic parameters. In the rat, CI-624 and CI-624 HC1 decrease secretion volumes and outputs of hydrogen, sodium and potassium ions and of pepsin. CI-624 antagonizes stress-induced gastric lesions in rats. In dogs, CI-624 antagonizes food-, insulin-and histamine-induced gastric secretion volume. The chemical also decreased histamine-induced acid and pepsin outputs and concentrations. The chemicals had no effect on acetylcholine-induced blood pressure changes in the dog but slightly potentiated those induced by 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP). CI-624 HCl did not block methacholine-induced chromodacryorrhea or produce mydriasis in the rat. Reserpine antagonized the antisecretory properties of CI-624 HCl, which could be the result of depletion of biologic amines involved in the gastric secretory mechanisms. It is concluded that the gastric antisecretory activity of CI-624 and CI-624 HCI is due to other mechanisms than the cholinergic system.