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.