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Potentiation by Metyrosine of Thioridazine Effects in Chronic Schizophrenics: A Long-Term Trial Using Double-Blind Crossover Technique

Potentiation by Metyrosine of Thioridazine Effects in Chronic Schizophrenics: A Long-Term Trial... Abstract • Four patients with chronic schizophrenia of stationary character were studied in order to titrate the lowest dose of thioridazine necessary for symptomatic control when the drug is given in combination with the inhibitor of catecholamine synthesis, metyrosine. The study showed 15% to 50% of the pretrial dose level of thioridazine hydrochloride was effective. In the present trial, the drug combination was maintained without any alterations in dosage for six months, and the therapeutic effect persisted unchanged. This treatment period was terminated by a doubleblind crossover design, and the activity of metyrosine was corroborated in all cases. Plasma drug concentrations and cerebrospinal fluid amine metabolites were measured. The data indicate that schizophrenic symptoms can be profoundly influenced by changes in catecholamine synthesis. Catecholamine-carrying neurons thus seem to be fundamentally involved in those brain functions that are disturbed in schizophrenia. The clinical usefulness of metyrosine in combination with neuroleptic agents deserves more extensive investigation. References 1. Carlsson A, Persson T, Roos BE, et al: Potentiation of phenothiazines by α-methyltyrosine in treatment of chronic schizophrenia . J Neural Transmission 33:83-90, 1972.Crossref 2. Carlsson A, Persson T, Roos BE, et al: Further studies on the mechanism of antipsychotic action: Potentiation by α-methyltyrosine of thioridazine effects in chronic schizophrenia . J Neural Transmission 34:125-132, 1973.Crossref 3. Bleuler E: Primäre und sekundäre Symptome der Schizophrenie . Z Neurol Psychiatr 124:606-646, 1930.Crossref 4. Wing JK: The measurement of behaviour in chronic schizophrenia . Acta Psychiatr Neurol Scand 35:245-254, 1960.Crossref 5. Wing JK: A simple subclassification of chronic schizophrenia . J Ment Sci 107:862-875, 1961. 6. Curry SH, Mould GP: Gas chromatographic identification of thioridazine in plasma and a method for routine assay of the drug . J Pharm Pharmacol 21:674-677, 1969.Crossref 7. Mårtensson E, Roos BE: Serum levels of thioridazine in mental patients and healthy volunteers . Eur J Clin Pharmacol 6:181-186, 1973.Crossref 8. Sjöström R, Roos BE: 5-Hydroxyindoleacetic acid and homovanillic acid in cerebrospinal fluid in manic-depressive psychosis . Eur J Clin Pharmacol 4:170-176, 1972.Crossref 9. Ahlenius S, Engel J: Behavioural effects of haloperidol after tyrosine hydroxylase inhibition . Eur J Pharmacol 15:187-192, 1971.Crossref 10. Ahlenius S, Engel J: On the interaction between pimozide and α-methyltyrosine . J Pharm Pharmacol 25:172-174, 1973.Crossref 11. Wålinder J, Carlsson A: Potentiation of neuroleptics by catecholamine inhibitors . Br Med J 1:551-552, 1973.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

Potentiation by Metyrosine of Thioridazine Effects in Chronic Schizophrenics: A Long-Term Trial Using Double-Blind Crossover Technique

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Publisher
American Medical Association
Copyright
Copyright © 1976 American Medical Association. All Rights Reserved.
ISSN
0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.1976.01770040061011
Publisher site
See Article on Publisher Site

Abstract

Abstract • Four patients with chronic schizophrenia of stationary character were studied in order to titrate the lowest dose of thioridazine necessary for symptomatic control when the drug is given in combination with the inhibitor of catecholamine synthesis, metyrosine. The study showed 15% to 50% of the pretrial dose level of thioridazine hydrochloride was effective. In the present trial, the drug combination was maintained without any alterations in dosage for six months, and the therapeutic effect persisted unchanged. This treatment period was terminated by a doubleblind crossover design, and the activity of metyrosine was corroborated in all cases. Plasma drug concentrations and cerebrospinal fluid amine metabolites were measured. The data indicate that schizophrenic symptoms can be profoundly influenced by changes in catecholamine synthesis. Catecholamine-carrying neurons thus seem to be fundamentally involved in those brain functions that are disturbed in schizophrenia. The clinical usefulness of metyrosine in combination with neuroleptic agents deserves more extensive investigation. References 1. Carlsson A, Persson T, Roos BE, et al: Potentiation of phenothiazines by α-methyltyrosine in treatment of chronic schizophrenia . J Neural Transmission 33:83-90, 1972.Crossref 2. Carlsson A, Persson T, Roos BE, et al: Further studies on the mechanism of antipsychotic action: Potentiation by α-methyltyrosine of thioridazine effects in chronic schizophrenia . J Neural Transmission 34:125-132, 1973.Crossref 3. Bleuler E: Primäre und sekundäre Symptome der Schizophrenie . Z Neurol Psychiatr 124:606-646, 1930.Crossref 4. Wing JK: The measurement of behaviour in chronic schizophrenia . Acta Psychiatr Neurol Scand 35:245-254, 1960.Crossref 5. Wing JK: A simple subclassification of chronic schizophrenia . J Ment Sci 107:862-875, 1961. 6. Curry SH, Mould GP: Gas chromatographic identification of thioridazine in plasma and a method for routine assay of the drug . J Pharm Pharmacol 21:674-677, 1969.Crossref 7. Mårtensson E, Roos BE: Serum levels of thioridazine in mental patients and healthy volunteers . Eur J Clin Pharmacol 6:181-186, 1973.Crossref 8. Sjöström R, Roos BE: 5-Hydroxyindoleacetic acid and homovanillic acid in cerebrospinal fluid in manic-depressive psychosis . Eur J Clin Pharmacol 4:170-176, 1972.Crossref 9. Ahlenius S, Engel J: Behavioural effects of haloperidol after tyrosine hydroxylase inhibition . Eur J Pharmacol 15:187-192, 1971.Crossref 10. Ahlenius S, Engel J: On the interaction between pimozide and α-methyltyrosine . J Pharm Pharmacol 25:172-174, 1973.Crossref 11. Wålinder J, Carlsson A: Potentiation of neuroleptics by catecholamine inhibitors . Br Med J 1:551-552, 1973.Crossref

Journal

Archives of General PsychiatryAmerican Medical Association

Published: Apr 1, 1976

References