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.