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. 1982 Jan;23(1):66–70. doi: 10.1136/gut.23.1.66

Effect of metoclopramide in guinea-pig ileum longitudinal muscle: evidence against dopamine-mediation.

M A Zar, O Ebong, D N Bateman
PMCID: PMC1419580  PMID: 7056499

Abstract

The investigation examines the hypothesis that metoclopramide-induced potentiation of gastrointestinal motility is mediated through dopamine receptors. In vitro studies on the longitudinal muscle of the guinea-pig ileum were performed. Metoclopramide, in concentrations comparable with those seen in plasma after therapeutic doses in man, selectively potentiated the cholinergic response Dopamine (1-100 microM) inhibited cholinergic transmission by inhibiting neuronal acetylcholine release. The inhibitory action of dopamine was antagonised by phentolamine, and alpha-adrenoceptor antagonist, but not by the dopamine receptor antagonists metoclopramide or primozide. Bromocriptine inhibited cholinergic responses by a postsynaptic mechanism which was not antagonised by metoclopramide, primozide, or phentolamine. The results are consistent with the view that metoclopramide-induced potentiation of gastrointestinal motility does not involve local dopamine receptors.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bateman D. N., Kahn C., Mashiter K., Davies D. S. Pharmacokinetic and concentration-effect studies with intravenous metoclopramide. Br J Clin Pharmacol. 1978 Nov;6(5):401–407. doi: 10.1111/j.1365-2125.1978.tb04604.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beani L., Bianchi C., Crema C. Effects of metoclopramide on isolated guinea-pig colon. 1. Peripheral sensitization to acetylcholine. Eur J Pharmacol. 1970;12(3):320–331. doi: 10.1016/0014-2999(70)90084-1. [DOI] [PubMed] [Google Scholar]
  3. Cegrell L., Falck B., Rosengren A. M. Dopamine and 5-hydroxytryptamine in the guinea-pig pancreas. Life Sci. 1967 Dec 1;6(23):2483–2489. doi: 10.1016/0024-3205(67)90311-6. [DOI] [PubMed] [Google Scholar]
  4. Day M. D., Blower P. R. Cardiovascular dopamine receptor stimulation antagonized by metoclopramide. J Pharm Pharmacol. 1975 Apr;27(4):276–278. doi: 10.1111/j.2042-7158.1975.tb10699.x. [DOI] [PubMed] [Google Scholar]
  5. Dolphin A., Jenner P., Marsden C. D., Pycock C., Tarsy D. Pharmacological evidence for cerebral dopamine receptor blockade by metoclopramide in rodents. Psychopharmacologia. 1975;41(2):133–138. doi: 10.1007/BF00421070. [DOI] [PubMed] [Google Scholar]
  6. Dougan D. F., Mearrick P. T., Wade D. N. Metoclopramide as a dopamine antagonist in the heart and gut of the mollusc Tapes watlingi. Clin Exp Pharmacol Physiol. 1974 Nov-Dec;1(6):473–478. doi: 10.1111/j.1440-1681.1974.tb00568.x. [DOI] [PubMed] [Google Scholar]
  7. Eisner M. Gastrointestinal effects of metoclopramide in man. In vitro experiments with human smooth muscle preparations. Br Med J. 1968 Dec 14;4(5632):679–680. doi: 10.1136/bmj.4.5632.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fontaine J., Reuse J. J. Pharmacological analysis of the effects of metoclopramide on the guinea-pig ileum in vitro. Arch Int Pharmacodyn Ther. 1973 Aug;204(2):293–305. [PubMed] [Google Scholar]
  9. Gibson A., Samini M. The effects of bromocriptine on pre-synaptic and post-synaptic alpha-adrenoceptors in the mouse vas deferens. J Pharm Pharmacol. 1979 Dec;31(12):826–830. doi: 10.1111/j.2042-7158.1979.tb13674.x. [DOI] [PubMed] [Google Scholar]
  10. Hay A. M., Man W. K. Effect of metoclopramide on guinea pig stomach: critical dependence on intrinsic stores of acetylcholine. Gastroenterology. 1979 Mar;76(3):492–496. [PubMed] [Google Scholar]
  11. Håkanson R., Owman C., Sjöberg N. O., Sporrong B. Amine mechanisms in enterochromaffin and enterochromaffin-like cells of gastric mucosa in various mammals. Histochemie. 1970;21(3):189–220. doi: 10.1007/BF00304213. [DOI] [PubMed] [Google Scholar]
  12. Klein R. L., Militello T. E., Ballinger C. M. Antiemetic effect of metoclopramide...evaluation in humans. Anesth Analg. 1968 May-Jun;47(3):259–264. [PubMed] [Google Scholar]
  13. Patil P. N., Burkman A. M., Yamauchi D., Hetey S. Analysis of the effects of apomorphine and bulbocapnine in relation to the proposed dopamine receptor. J Pharm Pharmacol. 1973 Mar;25(3):221–228. doi: 10.1111/j.2042-7158.1973.tb10628.x. [DOI] [PubMed] [Google Scholar]
  14. Paton W. D., Vizi E. S. The inhibitory action of noradrenaline and adrenaline on acetylcholine output by guinea-pig ileum longitudinal muscle strip. Br J Pharmacol. 1969 Jan;35(1):10–28. doi: 10.1111/j.1476-5381.1969.tb07964.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Paton W. D., Zar M. A. The origin of acetylcholine released from guinea-pig intestine and longitudinal muscle strips. J Physiol. 1968 Jan;194(1):13–33. doi: 10.1113/jphysiol.1968.sp008392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pinder R. M., Brogden R. N., Sawyer P. R., Speight T. M., Avery G. S. Metoclopramide: a review of its pharmacological properties and clinical use. Drugs. 1976;12(2):81–131. doi: 10.2165/00003495-197612020-00001. [DOI] [PubMed] [Google Scholar]
  17. Thorner M. O. Dopamine is an important neurotransmitter in the autonomic nervous system. Lancet. 1975 Mar 22;1(7908):662–665. doi: 10.1016/s0140-6736(75)91762-6. [DOI] [PubMed] [Google Scholar]

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