Summary
Seventeen mentually ill patients, most of them with schizophrenia, and one normal subject were treated with a-methyl-para-tyrosine, an inhibitor of tyrosine hydroxylase. Gradually increasing doses up to 2,000 mg daily were given for approximately 41 days.
This agent did not have any antipsychotic properties in these patients but it did have marked sedative effect. No parkinsonian symptoms or other side effects were seen. The significance of an agent such as a-methyl-para-tyrosine in the treatment of affective disorders (manic states) is discussed.
References
Corrodi, H., and L. C. F. Hanson: Central effects of an inhibitor of tyrosine hydroxylation. Psychopharmacologia (Berl.) 10, 116–125 (1966).
Hanson, L. C. F.: The disruption of conditioned avoidance response following depletion of brain catecholamines. Psychopharmacologia (Berl.) 8, 100–110 (1965).
Hornykiewicz, O.: Dopamine (3-hydroxy-tyramine) and brain function. Pharmacol. Rev. 18, 925–964 (1966).
Levitt, M., S. Spector, A. Sjoerdsma, and S. Udenfriend: Elucidation of the rate-limiting step in norepinephrine biosynthesis in the perfused guinea-pig heart. J. Pharmacol. exp. Ther. 148, 1–8 (1965).
Mennear, J. H., and A. D. Rudzik: The effects of amine depleting agents on the toxicity of amphetamine in aggregated mice. Life Sci. 5, 349–356 (1966).
Merck Sharp and Dohme Research Laboratories, West-Point, Pensylvania: MK-781, Preclinical Evaluation (1964).
Moore, K. E.: Effects of a-methyl-tyrosine on brain catecholamines and conditioned behavior in guinea pigs. Life Sci. 5, 55–65 (1966).
Nagatsu, T., M. Levitt, and S. Udenfriend: Tyrosine hydroxylase, the initial step in norepinephrine biosynthesis. J. biol. Chem. 239, 2910–2917 (1964).
Owen, J. A., B. Iggo, F. J. Scandrett, and C. P. Stewart: The determination of creatinine in plasma or serum, and in urine; a critical examination. Biochem. J. 58, 426–437 (1954).
Pisano, J. J., J. R. Crout, and D. Abraham: Determination of 3-methoxy-4-hydroxymandelic acid in urine. Clin. chim. Acta 7, 285–291 (1962).
Randrup, A., and I. Munkvad: Role of catecholamines in the amphetamine excitatory response. Nature (Lond.) 211, 540 (1966).
Rech, R. H., H. K. Borys, and K. E. Moore: Alterations in behavior and brain catecholamine levels in rats treated with a-methyltyrosine. J. Pharmacol. exp. Ther. 153, 412–419 (1966).
Schildkraut, J. J.: The catecholamine hypothesis of affective disorders: A review of supporting evidence. Amer. J. Psychiat. 122, 509–521 (1965–1966).
Sjoerdsma, A., K. Engelman, S. Spector, and S. Udenfriend: Inhibition of catecholamine synthesis in man with alpha-methyl-tyrosine, an inhibitor of tyrosine hydroxylase. Lancet 1965 II, 1092–1094.
—: Catecholamine-drug interaction in man. In scond Catecholamine Symposium. Pharmacol. Rev. 18, 673–683 (1966).
Spector, S., A. Sjoerdsma, and S. Udenfriend: Blockade of endogenous nor-epinephrine synthesis by a-methyl tyrosine, an inhibitor of tyrosine hydroxylase. J. Pharmacol. exp. Ther. 147, 86–95 (1965).
Thoenen, H., W. Haefely, K. F. Gey, and A. Huerlimann: The effect of a-methyl-tyrosine on peripheral sympathetic transmission. Life Sci. 5, 723–730 (1966).
Udenfriend, S., Discussion of H. Corrodi: Effects of tyrosine hydroxylase inhibitors on peripheral and central catecholamine stores. In Costa, E., L. J. Côté, and M. D. Yahr: Biochemistry and pharmacology of the basal ganglia. New York: Hewlett 1966.
Weissman, A., and B. K. Koe: Behavioral effects of L-a-methyl-tyrosine, an inhibitor of tyrosine hydroxylase. Life Sci. 4, 1037–1048 (1965).
— —, and S. S. Tenen: Antiamphetamine effect following inhibition of tyrosine hydroxylase. J. Pharmacol. exp. Ther. 151, 339–352 (1966).
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Charalampous, K.D., Brown, S. A clinical trial of a-Methyl-para-tyrosine in mentally ill patients. Psychopharmacologia 11, 422–429 (1967). https://doi.org/10.1007/BF00405026
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DOI: https://doi.org/10.1007/BF00405026