Antisecretory and antiulcer effect of T-330, a novel reversible proton pump inhibitor, in rats.
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.
Kinoshita
M
M
Department of Pharmacology, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Saito
N
N
Tamaki
H
H
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004942:Esophagitis, Peptic / Q000209:etiology / Q000503:physiopathology; D005744:Gastric Acid / Q000378:metabolism*; D005747:Gastric Fistula; D005753:Gastric Mucosa / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009853:Omeprazole / Q000494:pharmacology; D010437:Peptic Ulcer / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D054328:Proton Pump Inhibitors; D011725:Pyridines / Q000494:pharmacology*; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D006635:Histamine H2 Antagonists; D007093:Imidazoles; D054328:Proton Pump Inhibitors; D011725:Pyridines; C099138:T 330; D011899:Ranitidine; D009853:Omeprazole