Investigation into the possible influence of chlorinated amphetamine derivatives on 5-hydroxytryptamine synthesis in man
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In test animals, 4-chloro-N-methylamphetamine (CMA) and 4-chloro-amphetamine (4-CA) cause a decrease in the cerebral 5-HT and 5-HIAA concentrations; they exert no appreciable influence on catecholamine concentrations. In man, these compounds have a therapeutic effect on depression. In terms of antidepressant effect, they resemble not so much the nonchlorinated amphetamine derivatives as the true antidepressants.
This paper considers the question whether the influence of CMA and 4-CA on the 5-HT metabolism is based on inhibition of 5-HT synthesis. No arguments to support this hypothesis were found; findings obtained did support the postulate that these compounds are 5-HT depletors.
In conclusion, a possible explanation of the antidepressant effect of chlorinated amphetamine derivatives is offered.
Key-WordsSerotonin 4-Chlorinated Amphetamines Antidepressants Depression Central Stimulants
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- Bartholini, G., Blum, J. E., Pletscher, A. J.: Dopa induced locomotor stimulation of the inhibition of extracerebral decarboxylase. Pharm. Pharmac. 21, 297 (1969).Google Scholar
- —, Burkard, W. P., Pletscher, A., Bates, H. M.: Increase of cerebral catecholamines caused by 3,4-dihydroxyphenylalanine after inhibition of peripheral decarboxylase. Nature (Lond.) 215, 852 (1967).Google Scholar
- Coppen, A., Shaw, D. M., Farrel, J. P.: Potentiation of the antidepressive effect of a monoamine oxidase inhibitor by tryptophan. Lancet 1963 I, 79.Google Scholar
- Erspamer, V.: Occurrence of indolealkylamines in nature. In: 5-Hydroxytryptamine and related indolealkylamines, p. 132. Ed. V. Erspamer. Berlin-Heidelberg-New York: Springer 1966.Google Scholar
- Fuller, R. W., Hines, C. W., Mills, J.: Lowering of brain serotonin level by chloramphetamines. Biochem. Pharmacol. 14, 483 (1964).Google Scholar
- De Jonge, H.: Introduction to medical statistics. Proceedings of the Dutch Institute for Preventive Medicine, Leiden 1963.Google Scholar
- 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. (in press).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
- Lotti, V. J.: Potentiation of some central actions of L-dopa following inhibition of peripheral decarboxylase. Fed. Proc. 28, 642 (1969).Google 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. Eds. U. S. von Euler, S. Rosell, and B. Uvnäs. London: Pergamon Press 1966b.Google Scholar
- - Burkhard, W. P., Bruderer, H., Gey, K. F.: Decrease of cerebral 5-hydroxytryptamine and 5-hydroxyindoleacetic acid by an arylalkylamine. Life Sci. 828 (1963).Google Scholar
- Praag, H. M. van: A critical investigation into the possible significance of monoamine oxidase inhibition as the therapeutic principle in the treatment of depressions. Thesis, Utrecht 1962.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 (1969b).Google Scholar
- —, Korf, J., Woudenberg, F. van, Kits, T. P.: Influencing the human indoleamine metabolism by means of a chlorinated amphetamine derivative with anti-depressive effect (p-chloro-N-methylamphetamine). Psychopharmacologia (Berl.) 13, 145 (1968).Google Scholar
- - Schut, T.: A comparative investigation of the therapeutic effect of some 4-chlorinated amphetamine derivatives in depressive patients. (In preparation.)Google Scholar
- Sanders-Bush, E., Sulser, F.: On the mechanism of action of p-chloroamphetamine. Pharmacologist 11, 258 (1969).Google Scholar
- Strada, S. J., Sanders-Bush, E., Sulser, F.: Comparative studies on the mode of action of amphetamine and p-chloroamphetamine. Pharmacologist 11, 258 (1969).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