Pharmacological profile of UP 5145-52, an original antiulcer and antisecretory agent.
The gastric and antiulcer effects of UP 5145-52, a new naphthyridinone derivative (1-phenyl-1,2-dihydro-2-oxo-1,8-naphthyridin-3-yl)-4-acetoxy butane, were studied in rats. UP 5145-52 dose dependently prevented the formation of gastric lesions induced by a necrotizing agent such as absolute ethanol, indomethacin or stress (ED50 values were 0.065, 1.26 and 0.72 mg/kg p.o., respectively). A beneficial action was also observed against indomethacin-induced intestinal lesions. UP 5145-52 inhibited total acid output in the pylorus-ligated rat (ED50 on total acid output was 0.16 mg/kg p.o.) and in the rat chronic gastric fistula model. The mechanism of antisecretory activity currently remains unknown as UP 5145-52 fails to bind to receptors involved in gastric secretion (H2 or muscarinic) and to inhibit H+/K+ adenosine triphosphatase. The ability of UP 5145-52 (1 mg/kg p.o.) to restore synthesis of gastric acid glycoproteins depressed by previous administration of absolute ethanol suggests that cytoprotection could play a role in the antiulcer efficacy of the drug.
Dedieu-Chaufour
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Laboratoires Union Pharmacologique Scientifique Appliquée, Rueil-Malmaison, France.
Hertz
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Caussade
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Cloarec
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D000251:Adenosine Triphosphatases / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000633:toxicity; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology; D005755:Gastrins / Q000097:blood; D006168:Guinea Pigs; D007213:Indomethacin / Q000037:antagonists & inhibitors / Q000633:toxicity; D008297:Male; D009287:Naphthyridines / Q000494:pharmacology*; D010146:Pain / Q000517:prevention & control; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control
D000897:Anti-Ulcer Agents; D005755:Gastrins; D009287:Naphthyridines; D011957:Receptors, Opioid; C071319:UP 5145-52; D000431:Ethanol; D000251:Adenosine Triphosphatases; D007213:Indomethacin