title: Biochemical and pharmacological properties of a new proton pump inhibitor, 2-amino-4,5-dihydropyrido[1,2-a]thiazolo [5,4-g] benzimidazole (YJA20379-5).
abstract: This study was designed to determine biochemical and pharmacological properties of a newly synthesized benzimidazole derivative, 2-amino-4,5-dihydropyrido [1,2-a] thiazolo [5,4-g] benzimidazole (YJA20379-5) in vitro and in vivo. In the leaky membrane vesicles of pig gastric mucosa, YJA20379-5 inhibited the K(+)-stimulated H+,K(+)-ATPase activity in a concentration- and time-dependent manner, with IC50 values being 43 microM and 31 microM at pH 6.4 and 7.4, respectively. YJA20379-5, given intraduodenally, had a potent inhibitory effect on the gastric acid secretion in pylorus-ligated rats. The ED50 value for acid secretion was 15.4 mg/kg. YJA20379-5, administered orally, also suppressed gastric damages induced by water-immersion stress, indomethacin and ethanol, and duodenal damage induced by mepirizole in rats; the ED50 values were 17.6, 4.7, 3.0 and 18.7 mg/kg, respectively. Furthermore, repeated oral administration of YJA20379-5 accelerated the spontaneous healing of acetic acid-induced gastric ulcers in rats. It is concluded that the antisecretory activity of YJA20379-5 appears to be associated with inhibition of H+,K(+)-ATPase, while its antigastric and antiduodenal lesion activities are primarily related to the antisecretory effect.
authors.affiliation: Pharmacology and Toxicology Laboratory, Yung-Jin Pharmaceutical Co., Ltd.
authors.forename: S K
authors.initials: SK
authors.lastname: Sohn
authors.forename: M S
authors.initials: MS
authors.lastname: Chang
authors.forename: Y K
authors.initials: YK
authors.lastname: Chung
authors.forename: K B
authors.initials: KB
authors.lastname: Kim
authors.forename: T W
authors.initials: TW
authors.lastname: Wook
authors.forename: S G
authors.initials: SG
authors.lastname: Kim
authors.forename: W S
authors.initials: WS
authors.lastname: Choi
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D004840:Epirizole; D000431:Ethanol; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D007101:Immersion; D007213:Indomethacin; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D009853:Omeprazole / Q000494:pharmacology; D010437:Peptic Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D054328:Proton Pump Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000473:pathology; D013552:Swine; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D054328:Proton Pump Inhibitors; D013844:Thiazoles; C116952:YJA 20379-5; D004840:Epirizole; D000431:Ethanol; D009853:Omeprazole; D007213:Indomethacin