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.