1,6-Dimethyl-4-oxo-1,6,7,8,9,9a-hexahydro-4H-pyrido(1,2-a)- pyrimidine-3-carboxamide (Ch-127) protects against the intestinal damage in rats caused by two weeks' daily administration of indomethacin.
1,6-Dimethyl-4-oxo-1,6,7,8,9,9a-hexahydro-4H-pyrido 1,2-a pyrimidine-3-carboxamide (Ch-127) significantly inhibited the intestinal ulceration induced by a single dose of indomethacin (15 mg/kg p.o.). Moreover, indomethacin produced 75% lethality in the dose of 3.5 mg/kg p.o. administered daily for 2 weeks. The concurrent daily administration of Ch-127 (50 mg/kg p.o. +25 mg/kg s.c.) with indomethacin prevented the gastrointestinal mucosa from histologically detectable changes, and none of the animals died. The 80% lethality following the daily administration of naproxen (60 mg/kg p.o.) for two weeks was also significantly decreased by combining it with Ch-127 (50 mg/kg p.o.).
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004338:Drug Combinations; D007213:Indomethacin / Q000009:adverse effects*; D007410:Intestinal Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D009288:Naproxen / Q000009:adverse effects*; D011744:Pyrimidinones / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D014456:Ulcer / Q000139:chemically induced / Q000517:prevention & control
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D011744:Pyrimidinones; C020954:chinoin 127; D009288:Naproxen; D007213:Indomethacin