PT  - JOURNAL ARTICLE
AU  - Ueki, S
AU  - Seiki, M
AU  - Yoneta, T
AU  - Aita, H
AU  - Chaki, K
AU  - Hori, Y
AU  - Morita, H
AU  - Tagashira, E
AU  - Itoh, Z
TI  - Gastroprokinetic activity of nizatidine, a new H2-receptor antagonist, and its possible mechanism of action in dogs and rats.
DP  - 1993 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 152--157
VI  - 264
IP  - 1
4099  - http://jpet.aspetjournals.org/content/264/1/152.short
4100  - http://jpet.aspetjournals.org/content/264/1/152.full
SO  - J Pharmacol Exp Ther1993 Jan 01; 264
AB  - We studied the anti-acetylcholinesterase (AChE) activity of a new H2-antagonist, nizatidine, in in vitro experiments and its gastroprokinetic action in the dog and rat in comparison with other H2-antagonists, neostigmine and cisapride. The IC50 of nizatidine for AChE was 6.7 x 10(-6) M, and this activity was reversible. The relative anti-AChE potency was in the following order: neostigmine > nizatidine > cimetidine > famotidine. The inhibition of AChE by nizatidine was noncompetitive, with a Ki value of 7.4 x 10(-6) M. Gastrointestinal (GI) motility was examined during the interdigestive state in dogs with chronically implanted force transducers. Nizatidine (0.3-3 mg/kg, i.v.) significantly increased the motor index in a dose-dependent manner. It was of interest that the contractile response of the GI tract to nizatidine was similar to the interdigestive migrating contractions-like activity. At the doses used in this study, neither cimetidine nor famotidine had a significant effect on the motor index. Neostigmine at a higher dose of 0.06 mg/kg and cisapride at 0.3 mg/kg were found to stimulate GI contractions. Gastric emptying was determined in rats given phenol red as a liquid test meal. Nizatidine (3 mg/kg, i.p., or above) significantly increased gastric emptying, whereas the other H2-antagonists had no such effect. The ED50 and ED90 values of nizatidine for inhibition of gastric acid secretion were 0.18 and 3.22 mg/kg in dogs, and 2.94 and 19.6 mg/kg in rats, respectively. These findings suggest that nizatidine stimulates GI contractions and accelerates gastric emptying at gastric antisecretory doses.(ABSTRACT TRUNCATED AT 250 WORDS)