Abstract
“Some effects of the hallucinogenic drug, 2,5-dimethoxy-4-methyl amphetamine on the metabolism of biogenic amines in the rat brain”. B. E. Leonard, Pharmacology Section, Imperial Chemical Industries Limited, Pharmaceuticals Division, Alderly Park, Nr. Macclesfield, Cheshire.
In rats, 2,5-dimethoxy-4-methylamphetamine (DOM) caused piloerection, behavioural stimulation and pronounced “head twitching” in high doses (60 mg/kg). Lower doses had a less marked effect. DOM reduced the brain concentration of noradrenalin and elevated that of 5-hydroxytryptamine. Brain dopamine was initially elevated and then reduced by the drug. Tritiated tyrosine and tryptophan were used to study the effect of DOM on the rate of incorporation of these amino acids into the biogenic amines. It was found that DOM increased the rate of incorporation of tyrosine into noradrenaline but reduced the incorporation of tryptophan into 5-hydroxytryptamine. This effect on the “turnover” of noradrenalin and 5-hydroxy-tryptamine is shared by other hallucinogenic substances but not by the stimulant amphetamines.
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References
Andén, N.-E., Corrodi, H., Fuxe, K. B., Hökfelt, T.: Evidence for a central 5-hydroxytryptamine receptor stimulators by lysergic acid diethylamide. Brit. J. Pharmacol. 34, 1–7 (1968).
Anton, A. H., Sayre, D. F.: Distribution of metanephrine and normetanephrine in various animals and their analysis in diverse biologic material. J. Pharmacol. exp. Ther. 153, 15–29 (1966).
Baird, J. R. C., Lewis, T. J.: The effects of cocaine, amphetamine and some amphetamine-like compounds on the in vivo levels of noradrenalin and dopamine in the rat brain. Biochem. Pharmacol. 13, 1475–1842 (1964).
Carlsson, A., Corrodi, H., Fuxe, K., Hökfelt, T.: Effect of some antidepressant drugs on the depletion of intraneuronal brain catecholamine stores caused by 4α-dimethyl-meta-tyramine. Europ. J. Pharmacol. 5, 367–373 (1969).
Carlsson, A., Fuxe, K., Hamberger, B., Malmfors, T.: Effect of a new series of bicyclic compounds with potential thymoleptic properties on the reserpine resistant uptake mechanism of central and peripheral monoamine neurones in vitro and in vivo. Brit. J. Pharmacol. 36, 18–28 (1969).
Carlsson, A., Lindqvist, M., Dahlström, A., Fuxe, K. B., Masuoka, D.: Effects of the amphetamines group on intraneuronal brain amines in vivo and in vitro. J. Pharm. Pharmacol. 17, 521–524 (1965).
Costa, E., Groppetti, A., Revuelta, A.: Action of fenfluramine on monoamine stores of rat tissues. Brit. J. Pharmacol. 41, 57–64 (1971).
Denber, H. C. B., Teller, D. N.: Studies on mescaline XIX: A new theory concerning the nature of schizophrenia. Psychosomatics 9, 145–151 (1968).
Faillace, L. A., Snyder, S. H., Weingartner, H.: 2,4-dimethoxy-4-methylamphetamine: clinical evaluation of a new hallucinogenic drug. J. neuro. ment. dis. 150, 119–126 (1970).
Giarman, N. J., Freedman, D. X.: Biochemical aspects of the action of psychotomimetic drugs. Pharmacol. Rev. 17, 1–25 (1965).
Guroff, G., King, W., Udenfriend, S.: The uptake of tyrosine by rat brain in vitro. J. biol. Chem. 236, 1773–1777 (1961).
Hess, S., Udenfriend, S.: A fluorimetric procedure for the measurement of tryptamines in tissues. J. Pharmacol. exp. Ther. 127, 175–177 (1959).
Iversen, L. L., Axelrod, J., Glowinski, J.: The effect of antidepressant drugs on the uptake and metabolism of catecholamines in the brain. Proc. 5th Int. Congr.: Call. Int. Neuropsychopharmac, Washington, March 1966, ed. H. Brill, J. O. Cale, P. Deniker, H. Hippins, and P. B. Bradley, pp. 362–366. Amsterdam: Excerpta Medica Foundation 1967.
Koe, B. K., Weissman, A.: “p-Chlorophenylalanine: a specific depletor of brain serotonin”. J. Pharmacol. exp. Ther. 154, 499–516 (1966).
Knoll, J.: Psychotomimetic effects of amphetamines. In: Amphetamines and related compounds. Proc. Mario Negri Inst. for Pharmacological Research, Milan, Ed. E. Costa and S. Garattini, pp. 761–780. New York: Raven Press 1970.
Leonard, B. E.: The effect of four amphetamines on brain biogenic amines and their metabolites. Biochem. Pharmacol. 21, 1289–1297 (1971).
Leonard, B. E.: Some effects of the hallucinogenic drug, 2,5-dimethoxy-4-methyl-amphetamine on the metabolism of biogenic amines in the rat brain. Brit. J. Pharmacol. 45, 165P (1972).
Leonard, B. E., Shallice, S. A.: Some neurochemical effects of amphetamine, methyl-amphetamine and p-bromomethylamphetamine in the rat. Brit. J. Pharmacol. 41, 198–212 (1971a).
Leonard, B. E., Shallice, S. A.: The effect of p-nitromethylamphetamine on biogenic amines and amino acid precursors in the rat brain. Brit. J. Pharmacol. 43, 732–738 (1971b).
Leonard, B. E., Shallice, S. A.: The effects of some tryptamine derivatives on brain monoamines and their precursor amino acids. Neuropharmacology 11, 373–384 (1972).
Leonard, B. E., Tonge, S. R.: The effects of some hallucinogenic drugs upon the metabolism of noradrenaline. Life Sci. 8, pt. 1, 815–825 (1969).
Moore, K. E., Lariviere, E. W.: Effects of d-amphetamine and restraint on the content of norepinephrine and dopamine in rat brain. Biochem. Pharmacol. 15, 1497–1505 (1963).
Neff, N. H., Spano, P. F., Groppetti, A., Wang, C. T., Costa, E.: A simple procedure for calculating the synthesis rate of norepinephrine, dopamine and serotonin in rat brain. J. Pharmacol. exp. Ther. 176, 701–710 (1971).
Schubert, J., Nyback, H., Sedvall, G.: Effect of antidepressant drugs on accumulation and disappearance of monoamines formed in vivo from labelled precursors in mouse brain. J. Pharm. Pharmacol. 22, 136–139 (1970).
Snyder, S. H., Axelrod, T., Zweig, H.: A sensitive and specific fluorescence assay for tissue serotonin. Biochem. Pharmacol. 14, 831–835 (1965).
Snyder, S. H., Faillace, L. A. Hollister, L.: 2,5-Dimethoxy-4-methyl-amphetamine (STP): A new hallucinogenic drug. Science 158, 669–670 (1967).
Tonge, S. R., Leonard, B. E.: The effects of some hallucinogenic drugs upon the metabolism of 5-hydroxytryptamine in the brain. Life Sci. 8, pt. 1, 805–814 (1969).
Tonge, S. R., Leonard, B. E.: The effect of some hallucinogenic drugs on the amino acid precursors of brain monoamines. Life Sci. 9, pt. 1, 1327–1335 (1970).
Uchida, T. B., O'Brien, R. D.: The effect of hydrazides on rat brain 5-hydroxytryptamine, norepinephrine and γ-aminobutyric acid. Biochem. Pharmacol. 13, 725–730 (1964).
Udenfriend, S.: Fluorescence assay in biology and medicine. Molec. Biol. 3, 125–191 (1962).
Waalkes, T. P., Udenfriend, S.: A fluorimetric method for the estimation of tyrosine in plasma and tissues. J. Lab. clin. Med. 50, 733–736 (1957).
Wallach, M. B., Friedman, E., Gershon, S.: 2,5-dimethoxy-4-methylamphetamine (DOM), a neuropharmacological examination. J. Pharmacol. exp. Ther. 182, 145–154 (1972).
Wallach, M. N., Gershon, S.: A neuropsychopharmacological comparison of d-amphetamine, l-dopa and cocaine. Neuropharmacology 10, 743–752 (1971).
Welch, A. S., Welch, B. L.: Solvent extraction method for simultaneous determination of norepinephrine, dopamine, serotonin and 5-hydroxyindole acetic acid in a single mouse brain. Analyt. Biochem. 30, 161–179 (1969).
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Leonard, B.E. Some effects of the hallucinogenic drug 2,5-dimethoxy-4-methyl amphetamine on the metabolism of biogenic amines in the rat brain. Psychopharmacologia 32, 33–49 (1973). https://doi.org/10.1007/BF00421706
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DOI: https://doi.org/10.1007/BF00421706