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Nizatidine accelerates gastric emptying of a solid meal in rats

  • Esophageal, Gastric, and Duodenal Disorders
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Abstract

Nizatidine, a new histamine-2-receptor antagonist, stimulates gastrointestinal motility in dogs and gastric emptying of liquids in rats. Effect of nizatidine on gastric emptying of a solid meal was investigated using a novel gastric emptying model in rats. Male Wistar rats (weighing 200–300 g) were supplied with powdered food containing 30 w/w% barium 14 hr before the beginning of the experiment and x-ray photography of rat stomach was taken under light ether anesthesia. Gastric emptying was assessed by percentage of a decrease in area 30 min after drug was injected intraperitoneally. There was a positive correlation between the area of the gastric outline and the weight of the gastric contents (r=0.94,P<0.01). Ether anesthesia itself did not affect gastric emptying. Nizatidine increased gastric emptying dose-dependently (emptied percentage; vehicle: 4.9±1.5%, 1 mg/kg: 7.2±0.4%, 3 mg/kg: 10.4±2.0%, 10 mg/kg: 16.7±4.9%, 30 mg/kg: 25.7±7.4%).N-Desmethyl nizatidine (NDM) also stimulated gastric emptying, but nizatidineS-oxide, cimetidine, an famotidine had no significant effects on gastric emptying. Nizatidine and neostigmine, but not NDM, at a subthreshold dose accelerated gastric emptying treated with a low dose of acetylcholine (0.1 mg/kg). Atropine (2 mg/kg, −30 min) did not modulate the gastroprokinetic action of nizatidine, but blocked that of NDM. These findings suggest that this noninvasive method may allow measurement of gastric emptying of solids accurately and that nizatidine and NDM facilitate gastric emptying probably mediated by a direct and/or an indirect (acetylcholinesterase inhibition) cholinergic mechanism.

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References

  1. Lin T-M, Evans DC, Warrick MW, Pioch RP: Actions of nizatidine on the rat uterus, dog stomach and experimentally induced gastric lesions. J Pharmacol Exp Ther 239:400–405, 1986

    PubMed  Google Scholar 

  2. Lin T-M, Evans DC, Warrick MW, Pioch RP: Actions of nizatidine, a selective histamine H2-receptor antagonist, on gastric acid secretion in dogs, rats and frogs. J Pharmacol Exp Ther 239:406–410, 1986

    PubMed  Google Scholar 

  3. Price AH, Brogden RN: Nizatidine-A preliminary review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in peptic ulcer disease. Drugs 36:521–539, 1988

    PubMed  Google Scholar 

  4. Bertaccini G, Scarpignato C: Histamine H2-antagonists modify gastric emptying in the rat. Br J Pharmacol 77:443–448, 1982

    PubMed  Google Scholar 

  5. Galli A, Mantovani P, Pepeu G: Effect of ranitidine on ileal myenteric plexus preparation and on acetyl- and butyrylcholinesterase. Biochem Pharmacol 33:1845–1850, 1984

    PubMed  Google Scholar 

  6. Mizumoto A, Fujimura M, Iwanaga Y, Miyashita N, Yoshida N, Kondo Y, Itoh Z: Anticholinesterase activity of histamine H2-receptor antagonists in the dog. J Gastrointest Motil 2:273–280, 1990

    Google Scholar 

  7. Gwee MCE, Cheah LS: Actions of eimetidine and ranitidine at some cholinergic sites: Implications in toxicology and anesthesia. Life Sci 39:383–388, 1986

    PubMed  Google Scholar 

  8. Ohira Y, Hanyu N, Aoki T, Hashimoto Y, Iikura M, Fukuda S: Effects of various histamine H2-receptor antagonists on gastrointestinal motility and gastric emptying. J Smooth Muscle Res 29:131–142, 1993 (in Japanese)

    PubMed  Google Scholar 

  9. Ueki S, Seiki M, Yoneta T, Aita H, Chaki K, Hori Y, Morita H, Tagashira E, Itoh Z: Gastroprokinetic activity of nizatidine, a new H2-receptor antagonist, and its possible mechanism of action in dogs and rats. J Pharmacol Exp Ther 264:152–157, 1993

    PubMed  Google Scholar 

  10. Kounenis G, Voutsas D, Koutsoviti-Papadopoulou M, Elezoglou V: Inhibition of acetylcholinesterase by the H20receptor antagonist nizatidine. J Pharmacobiodyn 11:767–771, 1988

    PubMed  Google Scholar 

  11. Minami H, McCallum RW: The physiology and pathophysiology of gastric emptying in humans. Gastroenterology 86:1592–1610, 1984

    PubMed  Google Scholar 

  12. Robert A, Olafsson AS, Lancaster C, Zhang W: Interleukin-1 is cytoprotective, antisecretory, stimulates PGE2 synthesis by the stomach, and retards gastric emptying. Life Sci 48:123–134, 1991

    PubMed  Google Scholar 

  13. Matsuda M, Aono M, Moriga M, Okuma M: Centrally administered neuropeptide Y (NPY) inhibits gastric emptying and intestinal transit in the rat. Dig Dis Sci 38:845–850, 1993

    PubMed  Google Scholar 

  14. Breiter N, Sassy T: Development of methods for measuring the gastric emptying time of liquid and solid test meals in rats. Arzneim-Forsch/Drug Res 43:694–698, 1993 (in German)

    Google Scholar 

  15. Nowak TV, Roza AM, Weisbruch JP, Brosnan MR: Accelerated gastric emptying in diabetic rodents: Effect of insulin treatment and pancreas transplantation. J Lab Clin Med 123:110–116, 1994

    PubMed  Google Scholar 

  16. Houghton AD, Liepins P, Clarke SM, Mason RC: Effect of gastric resection, Roux-en-Y diversion and vagotomy on gastric emptying in the rat. Br J Surg 81:75–80, 1994

    PubMed  Google Scholar 

  17. Morton DM: Pharmacology and toxicology of nizatidine. Scand J Gastroenterol 22(suppl 136):1–8, 1987

    PubMed  Google Scholar 

  18. Sano H, Sato H, Furuta S, Motogi M, Matsuki Y: Pharmacokinetics of nizatidine in dogs and rats. Xenobiotica 21:1257–1264, 1991

    PubMed  Google Scholar 

  19. Kaneko H, Mitsuma T, Nagai H, Harada M, Kotera H, Furusawa A, Morise K: Effect of plaunotol on hypergastrinemia induced by long-term omeprazole administration in humans. Dig Dis Sci 40:160–165, 1995

    PubMed  Google Scholar 

  20. Kaneko H, Mitsuma T, Morise K, Uchida K, Furusawa A, Maeda Y, Nakada K, Adachi K: Effect of serotonin on the immunoreactive thyrotropin-releasing hormone concentrations of the rat stomach. Digestion 53:149–156, 1992

    PubMed  Google Scholar 

  21. River J, River C, Vale W: Synthetic competitive antagonists of corticotropin-releasing factor: Effect on ACTH secretion in the rat. Science 224:889–891, 1984

    PubMed  Google Scholar 

  22. Taché Y, Barquist E, Stephens RL, River J: Abdominal surgery- and trephination-induced delay in gastric emptying is prevented by intracisternal injection of CRF antagonist in the rat. J Gastrointest Motil 3:19–25, 1991

    Google Scholar 

  23. Cooke AR: Duodenal acidification: Role of the first part of duodenum in gastric emptying and secretion in dogs. Gastroenterology 67:85–92, 1974

    PubMed  Google Scholar 

  24. Scarpignato C, Tramacere R, Zappia L: Antisecretory and antiulcer effect of the H2-receptor antagonist famotidine in the rat: Comparison with ranitidine. Br J Pharmacol 92:153–159, 1987

    PubMed  Google Scholar 

  25. Decktor DL, Pendleton RG, Kellner AT, Davis MA: Acute effects of ranitidine, famotidine and omeprazole on plasma gastrin in the rat. J Pharmacol Exp Ther 249:1–5, 1989

    PubMed  Google Scholar 

  26. Cooke AR, Chvasta TE, Weisbrodt NW: Effect of pentagastrin on emptying and electrical and motor activity of the dog stomach. Am J Physiol 223:934–938, 1972

    PubMed  Google Scholar 

  27. Azuma J, Sawamura A, Harada H, Hamaguchi T, Takebe M, Mochizuki N, Shinomiya M, Seto Y: Phase I study of nizatidine (ZL-101) single oral administration. Jpn Pharmacol Ther 17:495–524, 1989

    Google Scholar 

  28. Kounenis G, Koutsoviti-Papadopoulou M, Elezoglou V: The excitatory effect of the new histamine H2-receptor antagonist nizatidine (LY 139037) on the guinea pig ileum. J Pharmacobiodyn 10:669–672, 1987

    PubMed  Google Scholar 

  29. Dubois A, Nompleggi D, Castell DO: Histamine H2 receptor stimulation increases gastric emptying in monkeys. Am J Physiol 255:G767-G771, 1988

    PubMed  Google Scholar 

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Kaneko, H., Mitsuma, T., Uchida, K. et al. Nizatidine accelerates gastric emptying of a solid meal in rats. Digest Dis Sci 40, 2043–2051 (1995). https://doi.org/10.1007/BF02208677

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  • DOI: https://doi.org/10.1007/BF02208677

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