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)

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 $IC_{50}$ values being $43{\mu}\textrm{M}$ and $43{\mu}\textrm{M}$ 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 $ED_{50}$ 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 $ED_{50}$ 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 a-ntisecretory 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.