, Volume 20, Issue 1, pp 66–76 | Cite as

A comparative study of the therapeutic effects of some 4-chlorinated amphetamine derivatives in depressive patients

  • H. M. van Praag
  • T. Schut
  • E. Bosma
  • R. van den Bergh
Human Pharmacology


The compounds 4-chloro-N-methylamphetamine (CMA) and 4-chloro-amphetamine (4-CA) are probably depletors of 5-hydroxytryptamine (5-HT). This has been demonstrated as plausible in human subjects also. In rat brains, the 5-HT depleting potency of 4-CA exceeds that of CMA. In depressive patients, moreover, CMA behaves as an antidepressant. In view of these findings the following two hypotheses were tested.

  1. 1.

    If there is any correlation between the 5-HT depleting potency of CMA and 4-CA on the one hand, and their antidepressant potency on the other, then the therapeutic potency of 4-CA must be expected to exceed that of CMA.

  2. 2.

    In view of the hypothesis of Carlsson et al. (1969) that the motor activating effect of antidepressants is of largely noradrenergic determination, and their mood-improving effect largely serotonergic, the effect of CMA and 4-CA on motility can be expected to be small, and their effect on mood therefore more or less selective.


We found no unequivocal confirmation of these hypothesis. The possible causes of this failure are discussed, and avenues of further investigation are outlined.


Chlorinated Amphetamines Antidepressants Serotonin Mood Elevation Motoricity 


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  1. Bunney, W. E., Davis, J. M.: Norepinephrine in depressive reactions. Arch. gen. Psychiat. 13, 483 (1965).PubMedGoogle Scholar
  2. Carlsson, A., Corrodi, H., Fuxe, K., Hökfelt, T.: Effect of antidepressant drugs in the depletion of intraneuronal brain 5-hydroxytryptamine stores caused by 4-methyl-β-ethyl metatyramine. Europ. J. Pharmacol. 5, 357 (1969).CrossRefGoogle Scholar
  3. Coppen, A., Shaw, D. M., Farrell, J. P.: Potentiation of the antidepressive effects of a monoamine oxidase inhibitor by tryptophan. Lancet 1963 I, 79.Google Scholar
  4. Frey, H. H.: p-Chloramphetamine similarities and dissimilarities to amphetamine. In: Amphetamine and related compounds. (E. Costa, and S. Garattini, ed.) New York: Raven Press 1970.Google Scholar
  5. —, Magnussen, M. P.: Different central mediation of the stimulant effects of amphetamine and its p-chloro analogue. Biochem. Pharmacol. 17, 1299 (1968).PubMedGoogle Scholar
  6. Fuller, R. W., Hines, C. W., Mills, J.: Lowering of brain serotonin level by chloramphetamines. Biochem. Pharmacol. 14, 483 (1965).CrossRefPubMedGoogle Scholar
  7. Glowinski, J., Axelrod, J.: Effect of drugs on the uptake, release and metabolism of H3-norepinephrine in the rat brain. J. Pharmacol. exp. Ther. 149, 43 (1965).PubMedGoogle Scholar
  8. — —: Effect of drugs on the disposition of H3- norepinephrine in the rat brain. Pharmacol. Rev. 18, 775 (1966).PubMedGoogle Scholar
  9. De Jonge, H.: Introduction to medical statistics. Proceedings of the Dutch Institute for Preventive Medicine, Leiden 1963.Google Scholar
  10. Kaergaard Nielsen, C., Magnussen, M. P., Kampmann, E., Frey, H. H.: Pharmacological properties of racemic and optically active p-chloroamphetamine. Arch. int. Pharmacodyn. 170, 428 (1967).PubMedGoogle Scholar
  11. Kits, T. P., Van Praag, H. M.: A controlled investigation of the antidepressive properties of p-chloro-N-methylamphetamine, a compound with selective influence on the metabolism of 5-hydroxytryptamine. Acta psychiat. scand. 46, 365 (1970).PubMedGoogle Scholar
  12. Lapin, T. P., Oxenburg, J. F.: Intensification of the central serotonergic processes as a possible determinant of the thymoleptic effect. Lancet 1969 I, 132.Google Scholar
  13. Miller, F. P., Cox, R. H., Jr., Snodgrass, W. R., Maickel, R. P.: Comparative effects of p-chlorophenylalaline, p-chloroamphetamine and chloro-N-methylamphetamine on rat brain norepinephrine, serotonin and 5-hydroxyindole-3-acetic acid. Biochem. Pharmacol. 19, 435 (1970).CrossRefPubMedGoogle Scholar
  14. Pletscher, A., Bartholini, G., Bruderer, H., Burkard, W. P., Gey, K. F.: Chlorinated arylalkylamines affecting the cerebral metabolism of 5-hydroxytryptamine. J. Pharmacol. exp. Ther. 145, 344 (1964).PubMedGoogle Scholar
  15. — —, Prada, M. da: Metabolism of monoamines by blood platelets and relation to 5-hydroxytryptamine liberation. In: Mechanisms of release of biogenic amines, pp. 165–175. U. S. von Euler, S. Rosell and B. Uvnäs, ed. London: Pergamon Press 1966b.Google Scholar
  16. —, Burkard, W. P., Bruderer, H., Gey, K. F.: Decrease of cerebral 5-hydroxytryptamine and 5-hydroxyindoleacetic acid by an arylalkylamine. Life Sci. 2, 828 (1963).CrossRefGoogle Scholar
  17. —, Prada, M. da, Burkard, W. P.: The effect of substituted phenylethylamines on the metabolism of biogenic amines. In: Amphetamines and related compounds. G. E. Costa and S. Garattini, ed. New York: Raven Press 1970.Google Scholar
  18. — — —, Bartholini, G., Steiner, F. A., Bruderer, H., Bigler, F.: Aralkylamines with different effect on the metabolism of aromatic monoamines. J. Pharmacol. exp. Ther. 154, 64 (1966a).PubMedGoogle Scholar
  19. Praag, H. M. van.: A critical investigation of the importance of monoamine oxidase inhibition and the therapeutic principle in the treatment of depression. Thesis, Utrecht 1962.Google Scholar
  20. —: Antidepressants, catecholamines and 5-hydroxyindoles. Trends towards a more specific research in the field of antidepressants. Psychiat. Neurol. Neurochir. 70, 219 (1967).PubMedGoogle Scholar
  21. —: Monoamines and depression. Reverse of the medal. Pharmacopsychiat. 2, 151 (1969).Google Scholar
  22. —, Kits, T. P., Schut, T., Dijkstra, P.: An attempt at indirect evaluation of the noradrenaline hypothesis. Results of a pilot study of the antidepressive qualities of p-chloro-N-methylamphetamine. Behav. Neuropsychiat. 1, 57 (1969).Google Scholar
  23. —, Korf, J., Woudenberg, F. van: Investigation into the possible influence of 4-chlorinated amphetamine derivatives and 5-hydroxytryptamine synthesis in man. Psychopharmacologia (Berl.) 18, 412 (1970).Google Scholar
  24. — — —, Kits, T. P.: Influencing the human indoleamine metabolism by means of a chlorinated amphetamine derivative with antidepressive effect (p-chloro-N-methylamphetamine). Psychopharmacologia (Berl.) 13, 145 (1968).Google Scholar
  25. —, Uleman, A. M., Spitz, J. C.: The vital syndrome interview. A structured standard interview for the recognition and registration of the vital depressive symptom complex. Psychiat. Neurol. Neurochir. 68, 329 (1965).PubMedGoogle Scholar
  26. Sanders-Bush, E., Sulser, F.: On the mechanism of action of p-chloroamphetamine. Pharmacologist 11, 258 (1969).Google Scholar
  27. — —: Biochemical consideration on the mode of action of p-chloroamphetamine. In: Amphetamines related compounds. (E. Costa and S. Garattini, ed.) New York: Raven Press 1970.Google Scholar
  28. Schildkraut, J. J.: The catecholamine hypothesis of affective disorders: a review of supporting evidence. Amer. J. Psychiat. 122, 509 (1965).PubMedGoogle Scholar
  29. —: Tranylcypromine effects on norepinephrine metabolism in rat brain. Amer. J. Psychiat. 126, 925 (1970).PubMedGoogle Scholar
  30. Verster, J., Praag, H. M. van: A comparative investigation of amphetamine and p-chloro-N-methylamphetamine in normal test persons. Pharmacopsychiat. 3, 239 (1970).Google Scholar

Copyright information

© Springer-Verlag 1971

Authors and Affiliations

  • H. M. van Praag
    • 1
  • T. Schut
    • 1
  • E. Bosma
    • 1
  • R. van den Bergh
    • 1
  1. 1.Departments of Biological Psychiatry and Clinical PsychologyPsychiatric University Clinic, State UniversityGroningenThe Netherlands

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