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.
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.
Sohn
S K
SK
Pharmacology and Toxicology Laboratory, Yung-Jin Pharmaceutical Co. Ltd., Hwasung-Kun, Kyunggi-Do, South Korea.
Chang
M S
MS
Choi
W S
WS
Kim
K B
KB
Woo
T W
TW
Lee
S B
SB
Chung
Y K
YK
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
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