The antisecretory and antiulcer effects of
T-330 (2-[(2-dimethylaminobenzyl)sulfinyl]-1-(3-methylpyridine-2-yl)
imidazole) , a novel reversible
proton pump inhibitor, were studied in rats.
T-330 suppressed
dibutyryl cyclic AMP-stimulated
acid formation in isolated rat gastric mucosal cells with the IC50 value of 0.57 microM. In chronic
fistula rats, intravenous, intraduodenal and
oral administration of
T-330 inhibited
pentagastrin-stimulated gastric acid secretion; the ED50 values calculated from the peak inhibition were 0.36, 0.43 and 0.73 mg/kg, respectively.
T-330 also reduced
dimaprit-stimulated gastric acid secretion following its intraduodenal injection (ED50 0.85 mg/kg). The antisecretory activities of
T-330 following its intraduodenal and
oral administration were 3-6- and 4-10-times more potent than those of
omeprazole and
ranitidine, respectively, while the duration of action of
T-330 was apparently shorter than that of
omeprazole and was almost equal to that of
ranitidine. Oral or duodenal administration of
T-330 inhibited the development of
acid-related damage (water-immersion- and
aspirin-induced gastric lesions,
cysteamine-induced
duodenal ulcers and
reflux esophagitis) with equal or higher potency than
omeprazole or
ranitidine. Furthermore,
T-330 prevented
ethanol-induced gastric lesions. These findings indicate that
T-330 exerts its antiulcer effect mainly via its potent antisecretory action and partly via its gastroprotective action.