title: Biochemical and pharmacological characteristics of a newly synthesized H+-K+ ATPase inhibitor, YJA20379-1, 2-amino-4,5-dihydro-8-phenylimidazole[2,1-b]thiazolo[5,4-g]benzothiazol e.
abstract: The biochemical and pharmacological characteristics of a newly synthesized H+-K+ ATPase inhibitor, 2-amino-4,5-dihydro-8-phenylimidazole[2,1-b]thiazolo[5,4-g]benzothiazole (YJA20379-1), were investigated. In the pig gastric microsomes, YJA20379-1 inhibited the gastric H+-K+ ATPase regardless of pH condition, IC50 values being 21 and 24 microM at pH 6.4 and 7.4, respectively. The inhibitory activity of YJA20379-1 was antagonized by dithiothreitol treatment but could not be reversed by dilution and washing of the enzyme preparation. In Sprague-Dawley rats, YJA20379-1, administered i.d., p.o, i.v., or s.c., significantly inhibited basal gastric acid secretion, with ED50 values of 4.7, 20.2, 6.3, and 13.4 mg/kg, respectively. The antisecretory action of YJA20379-1 was short lasting (less than 7 h at an oral dosing of 30 mg/kg). Oral administration of YJA20379-1 also prevented the formation of ethanol, indomethacin, and water immersion stress induced gastric lesions and mepirizole-induced duodenal ulcers in rats. Furthermore, YJA20379-1 accelerated the healing of acetic acid induced chronic gastric ulcers in rats. In conclusion, these results suggest that YJA20379-1 has a potent inhibitory activity on the gastric H+-K+ ATPase but much shorter duration of antisecretory action than omeprazole, thereby exerting its anti-ulcer effects partly with cytoprotective activity.
authors.affiliation: Pharmacology and Toxicology Laboratory, Yung-Jin Pharmaceutical Co. Ltd., Hwasung-Kun, Kyunggi-Do, South Korea.
authors.forename: S K
authors.initials: SK
authors.lastname: Sohn
authors.forename: M S
authors.initials: MS
authors.lastname: Chang
authors.forename: W S
authors.initials: WS
authors.lastname: Choi
authors.forename: K B
authors.initials: KB
authors.lastname: Kim
authors.forename: T W
authors.initials: TW
authors.lastname: Woo
authors.forename: S B
authors.initials: SB
authors.lastname: Lee
authors.forename: Y K
authors.initials: YK
authors.lastname: Chung
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D052160:Benzothiazoles; D004229:Dithiothreitol / Q000494:pharmacology; D004840:Epirizole / Q000633:toxicity; D000431:Ethanol / Q000633:toxicity; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D007213:Indomethacin / Q000633:toxicity; D008297:Male; D054328:Proton Pump Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine; D013844:Thiazoles / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000897:Anti-Ulcer Agents; D052160:Benzothiazoles; D007093:Imidazoles; D054328:Proton Pump Inhibitors; D013844:Thiazoles; C110270:YJA 20379-1; D004840:Epirizole; D000431:Ethanol; D004229:Dithiothreitol; D007213:Indomethacin