Influencing the human indoleamine metabolism by means of a chlorinated amphetamine derivative with antidepressive action (p-Chloro-N-Methylamphetamine)
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CMA (p-chloro-N-methylamphetamine) lowers the cerebral 5-HT concentration in test animals but has virtually no effect on the catecholamine concentrations. Moreover, this compound was found to behave in depressive patients like an antidepressive drug, not like a central stimulant of the amphetmine type. The study described was conducted in order to establish whether CMA influences the overall metabolism of indoleamines in man.
Such an influence was clearly demonstrable. Our findings are consistent with the hypothesis that CMA releases 5-HT from its depots. It has not been explained why a considerable proportion of the released 5-HT is excreted unchanged and why the increase in 5-HIAA excretion is so small: the overall activity of MAO was found not to be inhibited. No indications of abnormal 5-HT degradation were found at this time.
Patients with vital depressions who improved on CMA medication showed a lower 5-HIAA excretion before treatment than did patients who were refractory to CMA treatment. This is consistent with earlier observations. The possible cause of this phenomenon is discussed. Among the various possibilities considered, an abnormal 5-HT metabolism is regarded as the most plausible. Pertinent investigations are being continued.
Key-WordsIndoleamine Metabolism Psychopharmacology Antidepressive Drugs Amphetamine Derivatives (Chlorinated) Depression
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- Coppen, A.: The biochemistry of affective disorders. Brit. J. Psychiat. 113, 1237 to 1264 (1967).Google Scholar
- De Jonge, H.: Introduction to medical statistics. Proceedings of the Dutch Institute for Preventive Medicine, Leiden, 1963.Google Scholar
- Delorme, F., J. L. Froment et M. Jouvet: Suppression du sommeil par la p. chlorométhamphétamine et la p. chlorophénylalanine. C. R. Soc. Biol. (Paris) 160, 2347–2351 (1966).Google Scholar
- Erspamer, V.: Occurrence of indolealkylamines in nature. In: 5-Hydroxytryptamine and related indolealkylamines, pp. 132–181 (Ed.: V. Erspamer). Berlin-Heidelberg-New York: Springer 1966.Google Scholar
- —, and C. Ciceri: Action of reserpine on the 5-hydroxytryptamine (enteramine) biosynthesis and metabolism in dogs and rats. Experientia (Basel) 13, 87–88 (1957).Google Scholar
- Hanson, A.: Chemical analysis of indolealkylamines and related compounds, pp. 66–112. (Ed.: V. Erspamer). Berlin-Heidelberg-New York: Springer 1966.Google Scholar
- Haškovec, L., and K. Ryšánek: The action of reserpine in imipramine-resistant depressive patients. Clinical and biochemical study. Psychopharmalogia (Berl.) 11, 18–30 (1967).Google Scholar
- Jouvet, M., P. Bobillier, J. F. Pujol et J. Renault: Effects des lésions du système du raphé sur le sommeil et la sérotonine cérébrale, C. R. Soc. Biol. (Paris) 2343–2346 (1966).Google Scholar
- Oates, J. A.: In methods in medical research, Vol. 9, ed. by J. H. Quastel. Chicago: Year Book Medical Publishers Inc. 1961.Google Scholar
- Pletscher, A., G. Bartholini, and M. da Prada: 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 1966.Google Scholar
- Pletscher, A., W.P. Burkard, H. Bruderer, and K. F. Gey: Decrease of cerebral 5-hydroxytryptamine and 5-hydroxyindoleacetic acid by an arylalkylamine. Life Sci. 828–833 (1963).Google Scholar
- - T. P. Kits, D. Schut, and P. Dijkstra: An attempt at indirect evaluation of the noradrenaline hypothesis. Results of a pilot study of the antidepressive qualities of p-chloro-N-methylamphetamine. Int. J. Neuropsychiat. (In press 1968.)Google Scholar
- — and B. Leijnse: The influence of so-called monoamine-oxidase-inhibiting hydrazines on oral loading-tests with serotonin and 5-hydroxyindoleacetic acid. Psychopharmacologia (Berl.) 3, 202–203 (1962).Google Scholar
- — —: Die Bedeutung der Monoaminoxydasehemmung als antidepressives Prinzip. I. Psychopharmacologia (Berl.) 4, 1–14 (1963)Google Scholar
- — —: Die Bedeutung der Monoaminoxydasehemmung als antidepressives Prinzip. II. Psychopharmacologia (Berl.) 4, 91–102 (1963a).Google Scholar
- — —: Some aspects of the metabolism of glucose and of the non-esterified fatty acids in depressive patients. Psychopharmacologia (Berl.) 9, 220–233 (1966).Google Scholar
- Richter, D.: Tryptophan metabolism in mental illness. In: Amines and schizophrenia. Ed. by H.E. Himwich, S.S. Kety, and J.R. Smythies. London: Pergamon Press 1967.Google Scholar
- Udenfriend, S., H. Weissbach, and B. B. Brodie: In methods of biochemical analysis, Vol. 6, Ed. by D. Guck. New York: Interscience Publishers 1958.Google Scholar