Stimulation by nizatidine, a histamine H₂-receptor antagonist, of duodenal HCO₃^-secretion in rats: relation to anti-cholinesterase activity

Abstract

AIM To examine whether nizatidine stimulates duodenal HCO 3 -secretion in rats by inhibiting AChE activity. METHODS Under pentobarbital anesthesia, a proximal duodenal loop was perfused with saline, and the HCO 3 -secretion was measured at pH 7.0 using a pH-stat method and by adding 10mM HCl. Nizatidine, neostigmine, carbachol or famotidine was administered i.v. as a single injection. RESULTSIntravenous administration of nizatidine (3 -30mg/kg) dose-dependently increased duodenal HCO 3 -secretion, and the effect at 10mg/kg was equivalent to that obtained by carbachol at 0.01mg/kg. This nizatidine action was observed at the same dose range that inhibited acid secretion and enhanced gastric motility, mimicked by i.v. injection of neostigmine (0.03mg/kg), and significantly attenuated by bilateral vagotomy and prior s.c. administration of atropine but not by indomethacin, a cyclooxygenase inhibitor, or N G -nitro -L-arginine methyl ester, a NO synthase inhibitor. The HCO 3 -secretory response to acetylcholine (0.001mg/kg) was significantly potentiated by the concurrent administration of nizatidine (3mg/kg, i.v.). The IC 50 of nizatidine for AChE of rat erythrocytes was 1.4×10-6 M, about 12 times higher than that of neostigmine. Neither famotidine (>10 -3

Acotiamide attenuates central urocortin 2‐induced intestinal inflammatory responses, and urocortin 2 treatment reduces TNF‐α productions in LPS‐stimulated macrophage cell lines

“…Seto et al have reported that acotiamide suppressed the gene expression of neuromedin U, a known stress‐related neuropeptide. Acotimaide and drugs with anticholinesterase activity have also reported to stimulate duodenal bicarbonate secretion in rat models . Considering previous studies and our data, acotiamide may act directly on the gut and also indirectly through the brain‐gut axis such as ghrelin in the central nervous system …”

Effect of acotiamide on gastric emptying in healthy adult humans

“…In those days, several prokinetic agents such as dopamine 2 receptor antagonist and 5HT 4 receptor agonist were developed, and after elucidation of the mechanism of their effect on gastrointestinal regulatory systems, the clinical use of these agents was permitted. The investigators had originally obtained the idea for developing acotiamide from the AChE inhibition effect of nizatidine (H 2 ‐receptor antagonist) . The chemical structure of acotiamide actually resembles that of nizatidine in part.…”

“…idea for developing acotiamide from the AChE inhibition effect of nizatidine (H 2 -receptor antagonist) [19][20][21][22]. The chemical structure of acotiamide actually resembles that of nizatidine in part.…”

Influence of acid suppressants on gastric emptying: Cross‐over analysis in healthy volunteers

“…The effect of these drugs on the activity of gastroesophageal motility has not been fully investigated and there are conflicting data in the literature 37–47 . Ranitidine and nizatidine have been reported to have anticholinesterase activity and to increase acetylcholine concentration at the synapses of parasympathetic neurons 39,48 . Therefore, these drugs may increase gastrointestinal motor activity by stimulating parasympathetic tone.…”