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 inhibitor YJA20379-8, 3-butyryl-4-[R-1-methylbenzylamino]-8-ethoxy-1,7-naphthyridine, on gastric mucosal proton pump (H+/K+-ATPase) activity, gastric acid secretion 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 microM and 30.0 microM at pH 6.4 and pH 7.4, respectively. The effect was fully reversed by dilution and subsequent washing of the incubation mixtures of H+/K+-ATPase and YJA20379-8, suggesting the reversible nature of the enzyme inhibition. In pylorus-ligated rats, YJA20379-8 administered by different routes (intraduodenal, subcutaneous, 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). Pretreatment with YJA20379-8 also dose-dependently prevented gastric lesions induced by absolute ethanol and water-immersion stress in rats. These results suggest that YJA20379-8 might exert its antiulcer activity partly by reversible suppression of acid secretion and partly by protecting the gastric mucosa against ulcerative stimuli.
Sohn
S K
SK
Pharmacology and Toxicology Laboratory, Research and Development Centre, Yung-Jin Pharmaceutical Co. Ltd, Hwasung-Kun, Kyunggi-Do, Korea.
Chang
M S
MS
Choi
W S
WS
Chung
Y K
YK
Kim
K B
KB
Woo
T W
TW
Lee
S B
SB
Park
C J
CJ
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D000431:Ethanol / Q000633:toxicity; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D007101:Immersion; D066298:In Vitro Techniques; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D009287:Naphthyridines / Q000494:pharmacology*; D009853:Omeprazole / Q000494:pharmacology; D010437:Peptic Ulcer / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D054328:Proton Pump Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000150:complications
C114511:3-butyryl-4-(5R-methylbenzylamino)-8-ethoxy-1,7-naphthyridine; D004791:Enzyme Inhibitors; D009287:Naphthyridines; D054328:Proton Pump Inhibitors; D000431:Ethanol; D009853:Omeprazole