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]benzothiazole

The biochemical and pharmacological characteristics of a newly synthesized H+-K+ ATPase inhibitor, 2-amino-4,5-dihydro-8-phenylimidazole[2,1-b]thiazol o[5,4-g]benzothiazole (YJA20379-1), were investigated. In the pig gastric m icrosomes, YJA20379-1 inhibited the gastric H+-K+ ATPase regardless of pH c ondition, IC50 values being 21 and 24 mu M at pH 6.4 and 7.4, respectively The inhibitory activity of YJA20379-1 was antagonized by dithiothreitol tre atment but could not be reversed by dilution and washing of the enzyme prep aration. In Sprague-Dawley rats, YJA20379-1, administered i.d., p.o, i.v., or s.c., significantly inhibited basal gastric acid secretion, with ED50 va lues of 4.7, 20.2, 6.3, and 13.4 mg/kg, respectively. The antisecretory act ion 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 e thanol, indomethacin, and water immersion stress induced gastric lesions an d mepirizole-induced duodenal ulcers in rats. Furthermore, YJA20379-1 accel erated the healing of acetic acid induced chronic gastric ulcers in rats. I n conclusion. these results suggest that YJA20379-1 has a potent inhibitory activity on the gastric H+-K+ ATPase but much shorter duration of antisecr etory action than omeprazole, thereby exerting its anti-ulcer effects partl y with cytoprotective activity.