Gastric antisecretory and antiulcer/cytoprotective effects of 2-cyano-3-(ethylthio-3-methylthio)-2-propenoic acid methyl ester.
AY-28,200 (2-cyano-3-(ethylthio-3-methylthio)-2-propenoic acid methyl ester), a new gastric antisecretory/antiulcer agent, inhibited basal and pentagastrin-stimulated gastric acid secretion in the conscious rat (ED50 = 7.6 and 1.9 mg/kg i.g., respectively). For inhibition of basal secretion, peak activity was attained in 5 to 6 h after dosing and was maintained for more than 10 h, with no gastric antisecretory activity occurring at 24 h. The K+ stimulated H+-K+ ATPase activity from rabbit gastric microsomes was inhibited by AY-28,200 (IC50 = 22 mumol/l). AY-28,200 inhibited ethanol-induced gastric lesions, at 3 mg/kg p.o. AY-28,200's cytoprotective effects against ethanol lasted for more than 4 h. AY-28,200 blocked acetylsalicylic acid and stress-induced gastric ulcers but was inactive against indomethacin-induced gastric ulcers. These results suggest that AY-28,200 is a parietal cell proton pump inhibitor with cytoprotective properties, and may produce its cytoprotective effect by stimulating the formation of endogenous prostaglandins.
Borella
L E
LE
Wyeth-Ayerst Research, Inc., Princeton, NJ.
DiJoseph
J F
JF
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001241:Aspirin; D002927:Cimetidine / Q000494:pharmacology; D003487:Cyanoacrylates / Q000494:pharmacology*; D000431:Ethanol; D005744:Gastric Acid / Q000378:metabolism; D005746:Gastric Emptying / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D017506:H(+)-K(+)-Exchanging ATPase; D066298:In Vitro Techniques; D007213:Indomethacin; D008297:Male; D010418:Pentagastrin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced / Q000503:physiopathology; D013315:Stress, Psychological / Q000503:physiopathology
D000897:Anti-Ulcer Agents; D003487:Cyanoacrylates; C060544:2-cyano-3-(ethylthio-3-methylthio)-2-propenoic acid methyl ester; D000431:Ethanol; D002927:Cimetidine; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D010418:Pentagastrin; D001241:Aspirin; D007213:Indomethacin