A comparative study of the therapeutic effects of some 4-chlorinated amphetamine derivatives in depressive patients
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.
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.
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.
Key-WordsChlorinated Amphetamines Antidepressants Serotonin Mood Elevation Motoricity
Unable to display preview. Download preview PDF.
- 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
- 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
- De Jonge, H.: Introduction to medical statistics. Proceedings of the Dutch Institute for Preventive Medicine, Leiden 1963.Google Scholar
- 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
- 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
- — —, 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
- —, 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
- 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
- —: Monoamines and depression. Reverse of the medal. Pharmacopsychiat. 2, 151 (1969).Google Scholar
- —, 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
- —, 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
- — — —, 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
- Sanders-Bush, E., Sulser, F.: On the mechanism of action of p-chloroamphetamine. Pharmacologist 11, 258 (1969).Google Scholar
- — —: 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
- 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