Anti-ulcer activity of SKP-450, a novel potassium channel activator, in rats.
The anti-ulcer effects of SKP-450, a new potassium channel activator, were evaluated on basal and histamine-induced gastric acid secretion, and against experimentally-induced ulcers such as ethanol-induced and NaOH-induced gastric ulcers. In the pylorus-ligated rat, SKP-450 (0.1-0.5 mg kg(-1)) significantly decreased volume and concentration of gastric juice, and total acid output (ED(50): 0.12 mg kg(-1)). SKP-450 (0.3-3.0 mg kg(-1)) also inhibited histamine-induced gastric acid secretion, maximal effects being achieved at 1.0 mg kg(-1)(37.9% inhibition). In the 95% ethanol-treated rats, SKP-450 significantly reduced the mucosal lesions (46.9 and 31.4% inhibition at 0.1 and 0.2 mg kg(-1), respectively). A significant reduction in the ulcer index by SKP-450 was also observed in 0.3 n NaOH-treated rats (31.5 and 64.3% inhibition at 0.5 and 1.0 mg kg(-1), respectively). The effects of SKP-450 on histamine-induced acid secretion and on NaOH-induced ulcers were inhibited by glibenclamide (20 mg kg(-1), i.v.), a selective blocker of ATP-sensitive potassium channel. These results indicate that SKP-450 possesses anti-ulcer effects and its effects may be mediated by activation of ATP-sensitive potassium channels.
Cheon
H G
HG
Screening and Toxicology Research Center, *yn100, Jang-dong, Yusong, Taejon 305-343, Korea.
Kim
H J
HJ
Mo
H K
HK
Yoo
S E
SE
Lee
B H
BH
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D004195:Disease Models, Animal; D005744:Gastric Acid / Q000378:metabolism; D006633:Histamine Antagonists / Q000494:pharmacology; D008026:Ligation; D008297:Male; D015221:Potassium Channels / Q000819:agonists*; D011708:Pylorus / Q000502:physiology; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy*
D000897:Anti-Ulcer Agents; D001578:Benzopyrans; D006633:Histamine Antagonists; D015221:Potassium Channels; D011760:Pyrrolidinones; C096762:KR 30450