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 inhibitor, 3-butyryl-8-methoxy-4-[(2-thiophenyl)amino]quinoline (YJA20379-6), on gastric mucosal proton-pump (H+/K+-ATPase) activity, gastric acid secretion and gastroduodenal lesions in experimental rats. YJA20379-6 markedly inhibited H+/K+-ATPase activity in rabbit isolated gastric mucosal microsomes, confirming its classification as a proton-pump inhibitor. The inhibitory efficacy of YJA20379-6 on the proton pump was approximately 14-times higher than that of omeprazole at pH 7.4. YJA20379-6 given intraduodenally had a potent inhibitory effect on gastric secretion in pylorus-ligated rats (ED50 22.9 mg kg(-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 absolute ethanol, and the duodenal mucosa from damage induced by mepirizole. Repeated 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-ulcer effects which are exerted by suppression of H+/K+-ATPase activity in gastric parietal cells. YJA20379-6 might be useful for the clinical treatment of peptic ulcer diseases.
Kim
K B
KB
Pharmacology and Toxicology Laboratory, Yung-Jin Pharmaceutical Co. Ltd, Kyunggi-Do, Korea.
Chang
M S
MS
Chung
Y K
YK
Sohn
S K
SK
Kim
S G
SG
Choi
W S
WS
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D007213:Indomethacin; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009853:Omeprazole / Q000494:pharmacology*; D054328:Proton Pump Inhibitors; D011804:Quinolines / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D015149:Tocolytic Agents
D000897:Anti-Ulcer Agents; D054328:Proton Pump Inhibitors; D011804:Quinolines; D012997:Solvents; D015149:Tocolytic Agents; C114306:YJA 20379-6; D000431:Ethanol; D017506:H(+)-K(+)-Exchanging ATPase; D009853:Omeprazole; D007213:Indomethacin