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Antagonism of cisplatin-induced emesis by metoclopramide and dazopride through enhancement of gastric motility

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Abstract

The antiemetic activity, gastric motor activity, and dopamine receptor effects of metoclopramide, dazopride, and sulpiride were assessed to establish if enhancement of gastric motility or antagonism of central dopamine receptors is the predominant action for drug-induced suppression of cisplatin-induced emesis. Emesis produced in dogs by cisplatin is antagonized by metoclopramide and dazopride. The antiemetic actions of metoclopramide and dazopride are associated with their ability to enhance gastric motor activity. Dazopride, unlike metoclopramide, has minimal dopamine receptor antagonist properties. Sulpiride is a potent dopamine receptor antagonist; however, it had no effect on the stomach and was ineffective in suppressing cisplatin-induced emesis.

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References

  1. Gralla RJ: Metoclopramide: A review of antiemetic trials. Drugs 25(1):63–73, 1983

    Google Scholar 

  2. Harrington RA, Hamilton CW, Brogden RN, Linkewich JA, Romankiewicz JA, Heel RC: Metoclopramide. An updated review of its pharmacological properties and clinical use. Drugs 25(5):451–494, 1983

    Google Scholar 

  3. Akwari OE: The gastrointestinal tract in chemotherapy-induced emesis: A final common pathway. Drugs 25(1):18–34, 1983

    Google Scholar 

  4. Smith WL, Droppleman DA, Gregory RL, Alphin RS: Dazopride (AHR-5531), a novel gastrokinetic agent. Gastroenterology 86(5):1257, 1984

    Google Scholar 

  5. Johnson DN, Dannenburg WN: CNS effects of dazopride (AHR-5531), a new gastrokinetic agent. Gastroenterology 86(5):1126, 1984

    Google Scholar 

  6. Droppleman DA, Gregory RL, Alphin RS: A simplified method for assessing drug effects on gastric emptying in rats. J Pharmacol Methods 4:227–230, 1980

    Google Scholar 

  7. Bass P, Wiley JN: Contractile force transducer for recording muscle activity in unanesthetized animals. J Appl Physiol 32(4):467–570, 1977

    Google Scholar 

  8. Tedeschi DH, Tedeschi RW, Cook L, Mattes PA, Fellows EJ: The neuropharmacology of trifluoperazine: A potent psychotherapeutic agent. Arch Int Pharmacodyn 122:129–143, 1959

    Google Scholar 

  9. Litchfield JT, Wilcoxin F: A simplified method for evaluating dose-effect experiments. J Pharmacol Exp Ther 96:99–113, 1949

    Google Scholar 

  10. Oser BL: Hawk's Physiological Chemistry, 14th ed. New York, McGraw-Hill, 1965, pp 311–313

    Google Scholar 

  11. Lu KH, Amenomori Y, Chen CL, Meites J: Effects of central acting drugs on serum and pituitary prolactin levels in rats. Endocrinology 87:667–672, 1970

    Google Scholar 

  12. Kebabian JW, Calne DB: Multiple receptors for dopamine. Nature 277:93–96, 1979

    Google Scholar 

  13. Creese I, Leff SE: Dopamine receptors: A classification. J Clin Psychopharmacol 2(5):329–335, 1982

    Google Scholar 

  14. Leysen JE, Gommeren W, Laduron PM: Spiperone: A ligand of choice for neuroleptic receptors. Biochem Pharmacol 27:307–316, 1978

    Google Scholar 

  15. Watling KJ, Dowling JE: Dopaminergic mechanisms in the teleoste retina. I. Dopamine sensitive adenylate cyclase in homogenates of carp retina; effects of agonists, antagonists and ergots. J Neurochem 36:559–568, 1981

    Google Scholar 

  16. Brown BL, Albano JDM, Ekins RP, Sgherzi AM: A simple and sensitive saturation assay method for the measurement of adenosine 3′,5′-cyclic monophosphate, Biochem J 121:561–562, 1971

    Google Scholar 

  17. Gylys JA, Doran KM, Buyniski JP: Antagonism of cisplatin induced emesis in the dog. Res Commun Chem Pathol Pharmacol 23(1):61–68, 1979

    Google Scholar 

  18. Iwasaki Y, Kato Y, Chihara K, Ohgo S, Maeda K, Imura H: Effect of sulpiride on plasma prolactin in rats. Neuroendocrinology 21(3):267–274, 1976

    Google Scholar 

  19. Costall B, Naylor RJ: Is there a relationship between the involvement of extrapyramidal and mesolimbic brain areas with the cataleptic action of neuroleptic agents and their clinical antipsychotic effect? Psychopharmacologia 32:161–170, 1973

    Google Scholar 

  20. Borison HL, Wang SC: Physiology and pharmacology of vomiting. Pharmacol Rev 5:193–230, 1953

    Google Scholar 

  21. Borison HL, McCarthy LE: Neuropharmacology of chemotherapy-induced emesis. Drugs 25(1):8–17, 1983

    Google Scholar 

  22. Seigel L, Longo DL: The control of chemotherapy-induced emesis. Ann Intern Med 95(3):352–359, 1981

    Google Scholar 

  23. Laszlo J: Nausea and vomiting as a major complication of cancer chemotherapy. Drugs 25(1):1–7, 1983

    Google Scholar 

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Authors and Affiliations

  1. Research and Development Division, A.H. Robins Company, P.O. Box 26609, 23261-6609, Richmond, Virginia

    R. S. Alphin PhD, A. G. Proakis PhD, C. A. Leonard DSc, W. L. Smith PhD, W. N. Dannenburg PhD, W. J. Kinnier PhD, D. N. Johnson PhD, L. F. Sancilio PhD & J. W. Ward PhD

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  1. R. S. Alphin PhD
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  2. A. G. Proakis PhD
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  3. C. A. Leonard DSc
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  4. W. L. Smith PhD
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  5. W. N. Dannenburg PhD
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  6. W. J. Kinnier PhD
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  7. D. N. Johnson PhD
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  8. L. F. Sancilio PhD
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  9. J. W. Ward PhD
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Alphin, R.S., Proakis, A.G., Leonard, C.A. et al. Antagonism of cisplatin-induced emesis by metoclopramide and dazopride through enhancement of gastric motility. Digest Dis Sci 31, 524–529 (1986). https://doi.org/10.1007/BF01320319

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  • DOI: https://doi.org/10.1007/BF01320319

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