Pharmacological studies on the new quinoline derivative 1-(2-methylphenyl)-4-[(3-hydroxypropyl) amino]-6-trifluoromethoxy-2,3-dihydropyrrolo[3,2-c] quinoline with potent anti-ulcer effect.
The effects of the novel acylquinoline derivative, 1-(2-methylphenyl)-4-[(3-hydroxypropyl)amino]-6-trifluoromethoxy-2,3- dihydropyrrolo[3,2-c]quinoline (AU-006) on experimental ulcer models and on gastric secretion were examined. AU-006 prevented dose dependently gastric lesions induced by 95% ethanol when given orally (30-300 mg/kg). Similarly, gastric lesions caused by 0.3 N NaOH were inhibited by oral pretreatment with AU-006. To investigate the anti-ulcer mechanism of AU-006, the effect of AU-006 on gastric acid secretion was tested. Intraduodenal administration of AU-006 reduced in vivo gastric acid secretion. The protective effect of AU-006 against gastric lesions induced by ethanol was not affected by a nitric oxide synthase inhibitor, NG-nitro-L-arginine-methyl ester (l-NAME). In addition, the ethanol-induced mucus reduction was not recovered upon AU-006 administration. These results suggest that AU-006 is effective in the treatment of gastric ulcers by inhibiting gastric acid secretion, and that its activity is not related to either nitric oxide production or mucus secretion.
Cheon
H G
HG
Korea Research Institute of Chemical Technology, Pharmaceutical Screening Center, TaeJon, Korea.
Kim
H J
HJ
Kim
S S
SS
Choi
J K
JK
Kong
J Y
JY
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011708:Pylorus / Q000187:drug effects; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control
D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D011804:Quinolines; D019001:Nitric Oxide Synthase; C117172:AU 006