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Pharmaceutisch Weekblad

, Volume 2, Issue 1, pp 1121–1127 | Cite as

The acetylcholinesterase inhibitory activity of metoclopramide and some of its biotransformation products

  • G. Huizing
  • A. H. Beckett
Original Article
  • 16 Downloads

Abstract

Ki values were determined for thein vitro acetylcholinesterase inhibitory activity of the anti-emetic metoclopramide, some of its metabolic products and the newly synthesised N-(ethyl)-4-chlorobenzamide (1). Metoclopramide was a moderate inhibitor, 113 times more potent than 1 and 50 times less potent than physostigmine. Metabolic products of N-de-ethylation, N-di-de-ethylation, deamination followed by reduction and amide hydrolysis were increasingly less active as inhibitors. The implications of the present findings are briefly discussed.

Keywords

Public Health Ethyl Internal Medicine Amide Inhibitory Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Arita, T., R. Hori, K. Ito, K. Ichikawa andT. Uesugi (1970)Chem. Pharmn. Bull. 18, 1663.Google Scholar
  2. Bakke, O. M., andJ. Segura (1976)J. Pharm. Pharmacol. 28, 32.Google Scholar
  3. Beckett, A. H., andG. Huizing (1975)J. Pharm. Pharmacol. 27, Suppl. 42 P.Google Scholar
  4. Bergmann, F., andA. Shimoni (1952)Biochem. Biophys. Acta 9, 473.Google Scholar
  5. Cohen, J. B. (1949) In:Practical Organic Chemistry, 3rd ed. MacMillan and Co., London.Google Scholar
  6. Cowan, D. A., G. Huizing andA. H. Beckett (1976)Xenobiotica 6, 605.Google Scholar
  7. Eisner, M. (1968)Brit. Med. J. 4, 679.Google Scholar
  8. Elliot, P. N. C., P. Jenner, G. Huizing, C. D. Marsden andR. Miller (1977)Neuropharmacology 16, 333.Google Scholar
  9. Fontaine, J., andJ. Reuse (1978)Arch. Intern. Pharmacodyn. 235, 51.Google Scholar
  10. Hay, A. M. (1975)Gut 16, 403.Google Scholar
  11. Huizing, G., andA. H. Beckett (1980)Pharm. Weekblad Sci. Ed. 2, 1.Google Scholar
  12. Johnson, A. G. (1977) In:Metoclopramide ten years after (Huibregtse, K., Ed.) Excerpta Medica, Amsterdam.Google Scholar
  13. Kato, G., J. Yung andM. Ihnat (1970a)Mol. Pharmacol. 6, 588;Ibidem (1970b)Biochem. Biophys. Res. Commun. 40, 15.Google Scholar
  14. Mannering, G. J. (1972) In:Fundamentals of drug metabolism and drug disposition (La Du, B. N., H. G. Mandel andE. L. Way, Eds.) Williams and Wilkins, Baltimore.Google Scholar
  15. Michelson, M. J., andE. V. Zeimal (1973) In:Acetylcholine, an approach to the molecular mechanism of action. Pergamon Press, Oxford.Google Scholar
  16. Quintana, R. P. (1965)J. Pharm. Sci. 54, 462.Google Scholar
  17. Stanley, J. W., I. W. Matthison andJ. G. Beasly (1974)J. Med. Chem. 17, 8.Google Scholar
  18. Teng, L., R. B. Bruce andL. K. Dunning (1977)J. Pharm. Sci. 66, 1615.Google Scholar
  19. Vogel, A. I. (1956) In:A textbook of practical organic chemistry, 3rd ed. Longmans, Green and Co., London.Google Scholar
  20. Wilson, I. B., andJ. Alexander (1962)J. Biol. Chem. 237, 1323.Google Scholar

Copyright information

© Bohn, Scheltema & Holkema 1980

Authors and Affiliations

  • G. Huizing
    • 1
  • A. H. Beckett
    • 1
  1. 1.Department of Pharmacy, Chelsea CollegeUniversity of LondonLondonGreat Britain

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