, Volume 7, Issue 6, pp 391–399 | Cite as

Relation between the action of dopamine and apomorphine and their O-methylated derivatives upon the CNS

  • A. M. Ernst
Original Investigations


The syndrome of gnaw-compulsion was studied in rats providing evidence for a structure-effect relationship between the alcaloid apomorphine and the normal metabolite in the brain, dopamine.

The following tentative conclusions could be drawn from the available data:
  1. 1.

    The phenylethylamine-configuration with an OH-group at the para-position or at both the para- and meta-positions of the phenolring is essential for provoking a gnaw-compulsion syndrome;

  2. 2.

    Replacement of the OH-group at the para-position or at both the para- and meta-position by an OCH3-group antagonizes this effect and induces a hypokinetic state;

  3. 3.

    Occupation of the meta-position by an OH- or OCH3-group in the absence of similar groups at the para-position invariably causes a hyperkinesia.



Dopamine Apomorphine Similar Group Tentative Conclusion Normal Metabolite 
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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  1. Amsler, C.: Beiträge zur Pharmakologie des Gehirns. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 97, 1–14 (1923).Google Scholar
  2. Barbeau, A., and T. L. Sourkes: Some biochemical aspects of extrapyramidal diseases. Rev. Canad. Biol. 20, 197–203 (1962).Google Scholar
  3. Bertler, A., and E. Rosengren: On the distribution in brain of monoamines and of enzymes responsible for their formation. Experientia (Basel) 15, 382–384 (1959a).Google Scholar
  4. Birkmayer, W., u. O. Hornykiewicz: Der Dopa-Effekt bei der Parkinson-Akinese. Wien. klin. Wschr. 73, 787–788 (1961).Google Scholar
  5. Brücke, F. Th.: Beiträge zur Pharmakologie des Bulbocapnins. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 179, 504–523 (1935).Google Scholar
  6. Carlsson, A.: The occurrence, distribution and physiological role of catecholamines in the nervous system. Pharmacol. Rev. 11, 490–493 (1959).Google Scholar
  7. —, M. Lindquist, T. Magusson, and B. Waldeck: On the presence of 3-hydroxytyramine in brain. Science 127, 471 (1958).Google Scholar
  8. Divry et Evrard: Recherches sur certaines substances antagonistes de la bulbocapaine. J. belg. Neurol. Psychiat. 34, 506–523 (1934).Google Scholar
  9. Ehringer, H., u. O. Hornykiewicz: Verteilung von Noradrenalin und Dopamin im Gehirn des Menschen und ihr Verhalten bei Erkrankungen des extrapyramidalen Systems. Klin. Wschr. 38, 1236–1240 (1960).Google Scholar
  10. Ernst, A. M.: Phenomena of the Hypokinetic rigid type caused by O-methylation of Dopamine in the para-position. Nature (Lond.) 193, 178–179 (1962a).Google Scholar
  11. —: Experiments with an O-methylated product of Dopamine on cats. Acta physiol. pharmacol. neerl. 11, 48–53 (1962b).Google Scholar
  12. —: Relation between the structure of certain methoxyphenylethylaminederivatives and the occurrence of a hypokinetic rigid syndrome. Psychopharmacologia 7, 381–390 (1965).Google Scholar
  13. Everett, G. M., and R. G. Wiegand: Central amines and behavioral state: a critique and new data. Pharmacological Analysis of the Central Nervous Action, pp. 85–92, edit. W. Paton and P. Lindgren. Oxford: Pergamon Press 1962.Google Scholar
  14. Gerstenbrand, E., u. K. Pateisky: Über die Wirkung von L-Dopa auf die motorischen Störungen beim Parkinson-Syndrom. Wien. Z. Nervenheilk. 20, 90–100 (1962).Google Scholar
  15. Holtz, P.: Role of L-dopa decarboxylase in the biosynthesis of catecholamines in nervous tissue and the adrenal medulla. Pharmacol. Rev. 11, 317–329 (1959).Google Scholar
  16. Rossum, J. M. v., and J. A. Th. M. Hurkmans: Mechanism of action of psychomotor stimulant drugs. Int. J. Neuropharmacol. 3, 227–239 (1964).Google Scholar
  17. Sano, I., K. Taniguchi, T. Gamo, M. Takesada u. Y. Kakimoto: Die Katechinamine im Zentralnervensystem. Klin. Wschr. 38, 57–62 (1960).Google Scholar
  18. Sourkes, Z. L.: Biochemistry of mental disease. New York: Hoeber (Harper and Row) 1962.Google Scholar
  19. —: Cerebral and other diseases with disturbance of amine metabolism. Progress in Brain Research. Biogenic Amines, pp. 186–200, edit. H. E. Himwich and W. A. Himwich. Amsterdam: Elsevier 1964.Google Scholar

Copyright information

© Springer-Verlag 1965

Authors and Affiliations

  • A. M. Ernst
    • 1
  1. 1.Department of PharmacologyUtrecht State UniversityUtrechtThe Netherlands

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