Effects of KW-5338 (domperidone) on gastric motility

The effects of KW-5338 (domperidone) on gastric motility were studied by the balloon method in pentobarbital anesthetized mongrel dogs. KW-5338 was found to enhance the antrum motility. Its enhancement pattern showed the following characteristics: (1) The tonus was not affected, (2) the contraction pressure increased, (3) the frequency of contraction decreased slightly, and (4) the enhancement was long lasting. Metoclopramide showed strong but short enhancement of antrum motility. KW-5338 augmented also the gastric body motility, although the enhancement pattern was different from that in the antrum: (1) The action did not last so long, and (2) an increase in tonus was observed. The augmentation of the gastric motility by KW-5338 was observed even after vagotomy and splanchnicotomy, but it was weaker and shorter than in the intact state. THe KW-5338 induced augmentation was diminished by tetrodotoxin treatment. The gastric relaxation response to dopamine was blocked by KW-5338. These results show that KW-5338 activates the gastric motility not only by central mechanism but also by stimulation to intramural neurons. The dopamine blocking activity of KW-5338 might play some role in the enhancement of gastric motility.