Skip to main content
Log in

A clinical trial of a-Methyl-para-tyrosine in mentally ill patients

  • Short Communications
  • Published:
Psychopharmacologia Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  • Corrodi, H., and L. C. F. Hanson: Central effects of an inhibitor of tyrosine hydroxylation. Psychopharmacologia (Berl.) 10, 116–125 (1966).

    Google Scholar 

  • Hanson, L. C. F.: The disruption of conditioned avoidance response following depletion of brain catecholamines. Psychopharmacologia (Berl.) 8, 100–110 (1965).

    Google Scholar 

  • Hornykiewicz, O.: Dopamine (3-hydroxy-tyramine) and brain function. Pharmacol. Rev. 18, 925–964 (1966).

    PubMed  Google Scholar 

  • 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).

    PubMed  Google Scholar 

  • 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).

    Article  PubMed  Google Scholar 

  • 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).

    Article  PubMed  Google Scholar 

  • Nagatsu, T., M. Levitt, and S. Udenfriend: Tyrosine hydroxylase, the initial step in norepinephrine biosynthesis. J. biol. Chem. 239, 2910–2917 (1964).

    PubMed  Google Scholar 

  • 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).

    PubMed  Google Scholar 

  • 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).

    Article  PubMed  Google Scholar 

  • Randrup, A., and I. Munkvad: Role of catecholamines in the amphetamine excitatory response. Nature (Lond.) 211, 540 (1966).

    Google Scholar 

  • 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).

    PubMed  Google Scholar 

  • Schildkraut, J. J.: The catecholamine hypothesis of affective disorders: A review of supporting evidence. Amer. J. Psychiat. 122, 509–521 (1965–1966).

    Google Scholar 

  • 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.

    Google Scholar 

  • —: Catecholamine-drug interaction in man. In scond Catecholamine Symposium. Pharmacol. Rev. 18, 673–683 (1966).

    PubMed  Google Scholar 

  • 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).

    PubMed  Google Scholar 

  • 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).

    Article  PubMed  Google Scholar 

  • 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.

    Google Scholar 

  • Weissman, A., and B. K. Koe: Behavioral effects of L-a-methyl-tyrosine, an inhibitor of tyrosine hydroxylase. Life Sci. 4, 1037–1048 (1965).

    Article  PubMed  Google Scholar 

  • — —, and S. S. Tenen: Antiamphetamine effect following inhibition of tyrosine hydroxylase. J. Pharmacol. exp. Ther. 151, 339–352 (1966).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00405026

Keywords

Navigation