Antisecretory and antiulcer effect of T-330, a novel reversible proton pump inhibitor, in rats

• Published in: European journal of pharmacology Vol. 321; no. 3; pp. 325 - 332
• Main Authors: Kinoshita, Mine, Saito, Nobuko, Tamaki, Hajime
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 05.03.1997; Elsevier
• Subjects: Animals; Anti-Ulcer Agents - pharmacology; Biological and medical sciences; Digestive system; Enzyme Inhibitors - pharmacology; Esophagitis, Peptic - etiology; Esophagitis, Peptic - physiopathology; Gastric Acid - metabolism; Gastric acid secretion; Gastric Fistula; Gastric Mucosa - metabolism; H +/K +-ATPase; Histamine H2 Antagonists - pharmacology; Imidazoles - pharmacology; Male; Medical sciences; Omeprazole; Omeprazole - pharmacology; Peptic Ulcer - chemically induced; Peptic Ulcer - physiopathology; Peptic Ulcer - prevention & control; Pharmacology. Drug treatments; Proton Pump Inhibitors; Pyridines - pharmacology; Ranitidine; Ranitidine - pharmacology; Rats; Rats, Sprague-Dawley; T-330; Omeprazole; Gastric acid secretion; T-330; H +/K +-ATPase; Ranitidine; Rat; Antiulcer agent; Proton pump inhibitor; Antisecretory agent; Ulcer; Intraduodenal administration; Gastric disease; Stomach; Digestive system; Rodentia; Oral administration; Mucous cell; In vitro; In vivo; Vertebrata; Chemotherapy; Experimental disease; Mammalia; Treatment; Animal; Digestive diseases; Comparative study; Gastric juice
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(96)00958-2

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 IC 50 value of 0.57 μM. In chronic fistula rats, intravenous, intraduodenal and oral administration of T-330 inhibited pentagastrin-stimulated gastric acid secretion; the ED 50 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 (ED 50 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.