The mechanism of cytoprotective effect of CHINOIN-127.
According earlier, investigations nitrogen bridgehead compounds make a representative group of non-prostaglandin type gastroprotective agents. One member of this group is CHINOIN-127 (1,6-dimethyl-4-oxo-1, 6, 7, 8, 9, 9a-hexahydro-4H-pyrido-(1, 2a)-pyrimidine-3-carbox-amide). CHINOIN-127 is a potent non-narcotic analgesic and antiinflammatory agent and has a remarkable protective effect on indomethacin induced ulcer (ED50 = 25 mg/kg p.o.) and on acidified ethanol induced ulcer (ED50 = 26 mg/kg p.o.). In this study we examined the mechanism of action of cytoprotective effect of this drug and we made a comparison between the cytoprotective effect of 20% ethanol and 25 mg/kg CHINOIN-127. In the gastric mucosa of control rats we observed a balance between TxA2 and PGI2 (PGI2/TxA2 = 3.8) and between the cytoprotective prostaglandins (PGI2 and PGE2) and ulcerogen eicosanoids (TxA2 and leukotrienes) (PGI2 + PGE2/TxA2 + LTs = 3.9). 100% ethanol treatment causes disintegration of this balance, shifting the synthesis towards the ulcerogen eicosanoids production. CHINOIN-127 and 20% ethanol pretreatment improves the deranged balance between cytoprotective prostaglandins and ulcerogen eicosanoids. Our results demonstrate that CHINOIN-127 and 20% ethanol have a similar mechanism of cytoprotective action on ethanol induced ulcer in rats.
Department of Pharmacology, Semmelweis University, Medical School, Budapest, Hungary.
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Kapui
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Boér
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Hermecz
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Gyíres
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D011464:Epoprostenol / Q000378:metabolism; D000431:Ethanol; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D011744:Pyrimidinones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D013929:Thromboxane B2 / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D011744:Pyrimidinones; D000431:Ethanol; D013929:Thromboxane B2; C020954:chinoin 127; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol