Biochemical and pharmacological characteristics of 3-butyryl-8-methoxy-4-[(2-thiophenyl)amino]quinoline, a new proton-pump inhibitor, in rabbit gastric microsomes and in rats

We have investigated the properties of the newly synthesized proton-pump in hibitor, 3-butyryl-8-methoxy-4-[(2-thiophenyl) amino] quinoline (YJA20379-6 ), on gastric mucosal proton-pump (H+/K+-ATPase) activity, gastric acid sec retion and gastroduodenal lesions in experimental rats. YJA20379-6 markedly inhibited H+/K+-ATPase activity in rabbit isolated gast ric mucosal microsomes, confirming its classification as a proton-pump inhi bitor. The inhibitory efficacy of YJA20379-6 on the proton pump was approxi mately 14-times higher than that of omeprazole at pH 7.4. YJA20379-6 given intraduodenally had a potent inhibitory effect on gastric secretion in pylo rus-ligated rats (ED50 22.9 mgkg(-1)) but was less active than omeprazole. Pretreatment of rats with YJA20379-6 dose-dependently protected the gastric mucosa from damage induced by water-immersion stress, indomethacin and abs olute ethanol, and the duodenal mucosa from damage induced by mepirizole. R epeated administration of YJA20379-6 also dose-dependently accelerated the spontaneous healing of acetic acid-induced gastric ulcers. These results suggest that YJA20379-6 has potent anti-secretory and anti-ul cer effects which are exerted by suppression of H+/K+-ATPase activity in ga stric parietal cells. YJA20379-B might be useful for the clinical treatment of peptic ulcer diseases.