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Anti-ulcer activity of SKP-450, a novel potassium channel activator, in rats.

Abstract
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.
AuthorsH G Cheon, H J Kim, H K Mo, S E Yoo, B H Lee
JournalPharmacological research (Pharmacol Res) Vol. 40 Issue 3 Pg. 243-8 (Sep 1999) ISSN: 1043-6618 [Print] Netherlands
PMID10479468 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 1999 Academic Press.
Chemical References
  • Anti-Ulcer Agents
  • Benzopyrans
  • Histamine Antagonists
  • Potassium Channels
  • Pyrrolidinones
  • KR 30450
Topics
  • Animals
  • Anti-Ulcer Agents (pharmacology)
  • Benzopyrans (pharmacology)
  • Disease Models, Animal
  • Gastric Acid (metabolism)
  • Histamine Antagonists (pharmacology)
  • Ligation
  • Male
  • Potassium Channels (agonists)
  • Pylorus (physiology)
  • Pyrrolidinones (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Stomach Ulcer (chemically induced, drug therapy)

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