Biochemical and pharmacological characteristics of a newly synthesized H+/K+-ATPase inhibitor, YJA20379-8, 3-butyryl-4[R-1-methylbenzylamino]-8-ethoxy-1,7-naphthyridine, in pigs and rats

We have investigated the effect of the newly synthesized proton-pump inhibi tor YJA20379-8, 3-butyryl-4-[R-1-methylbenzylamino]-8-ethoxy-1,7-naphthyrid ine, on gastric mucosal proton pump (H+/K+-ATPase) activity, gastric acid s ecretion and gastric lesions in experimental animals. In lyophilized pig gastric microsomes, YJA20379-8 was shown to inhibit H+/K +-ATPase activity; the inhibitory effect was not affected by pH, the IC50 ( dose resulting in 50% inhibition) being 28.0 mu M and 30.0 mu M at pH 6.4 a nd pH 7.4, respectively. The effect was fully reversed by dilution and subs equent washing of the incubation mixtures of H+/K+-ATPase and YJA20379-8, s uggesting the reversible nature of the enzyme inhibition. In pylorus-ligate d rats, YJA20379-8 administered by different routes (intraduodenal, subcuta neous, intravenous or oral) resulted in dose-dependent suppression of basal gastric acid secretion. The duration of antisecretory action of 30 mg kg(- 1) YJA20379-8 given intraduodenally was very brief (less than 7 h). Pretrea tment with YJA20379-8 also dose-dependently prevented gastric lesions induc ed by absolute ethanol and water-immersion stress in rats. These results suggest that YJA20379-8 might exert its antiulcer activity pa rtly by reversible suppression of acid secretion and partly by protecting t he gastric mucosa against ulcerative stimuli.