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

Abstract

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.

• Authors: M Kinoshita, N Saito, H Tamaki
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 321 Issue 3 Pg. 325-32 (Mar 05 1997) ISSN: 0014-2999 [Print] Netherlands
• PMID: 9085044 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anti-Ulcer Agents
• Enzyme Inhibitors
• Histamine H2 Antagonists
• Imidazoles
• Proton Pump Inhibitors
• Pyridines
• T 330
• Ranitidine
• Omeprazole

Topics

• Animals
• Anti-Ulcer Agents (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Esophagitis, Peptic (etiology, physiopathology)
• Gastric Acid (metabolism)
• Gastric Fistula
• Gastric Mucosa (metabolism)
• Histamine H2 Antagonists (pharmacology)
• Imidazoles (pharmacology)
• Male
• Omeprazole (pharmacology)
• Peptic Ulcer (chemically induced, physiopathology, prevention & control)
• Proton Pump Inhibitors
• Pyridines (pharmacology)
• Ranitidine (pharmacology)
• Rats
• Rats, Sprague-Dawley