The present study was undertaken to clarify a prokinetic activity of nizatidine (CAS 76963-41-2) during the digestive state as well as gastric emptying of a solid test meal in comparison with cimetidine (CAS 51481-61-9), famotidine (CAS 76842-35-6) and cisapride (CAS 81098-60-4). Intravenous administration of nizatidine (0.3-3 mg/kg) enhanced the motility of the gastric antrum and duodenum during the digestive state. With cimetidine (1-10 mg/kg) and famotidine (0.1-1 mg/kg) enhancement of gastric motility was observed only with the highest dose of cimetidine, and famotidine had no effect. Marked enhancement of gastric motility was observed with cisapride (0.1-0.5 mg/kg). After intraduodenal administration of nizatidine (10 and 20 mg/kg) and cisapride (0.25 and 0.5 mg/kg), they also amplified the contractile activity of the gastric antrum. Gastric emptying of a solid test meal was accelerated by intraperitoneal administration of nizatidine (1-10 mg/kg) to the same extent as cisapride (0.1-1 mg/kg). In addition, even in a model of delayed gastric emptying induced by clonidine, nizatidine, like cisapride, improved the rate of gastric emptying. Neither cimetidine (3-30 mg/kg) nor famotidine (0.3-3 mg/kg) affected the gastric emptying of a solid meal or delayed gastric emptying. These results suggest that nizatidine enhanced gastric motility even during the digestive state, and accelerated gastric emptying of a solid meal, similar to cisapride. Furthermore, nizatidine improved clonidine-induced delayed gastric emptying. These prokinetic activities of nizatidine may by useful for the treatment of abdominal symptoms due to dysmotility and delayed gastric emptying in patients with gastritis and non-ulcer dyspepsia (NUD). In comparison with famotidine and cimetidine, nizatidine may be different from other histamine H2-receptor antagonists and has unique properties other than its gastric antisecretory activity.