Inhibition of dopamine synthesis in chronic schizophrenia. Clinical ineffectiveness of metyrosine.
Article Details
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Nasrallah HA, Donnelly EF, Bigelow LB, Rivera-Calimlim L, Rogol A, Potkin S, Rauscher FP, Wyatt RJ
Inhibition of dopamine synthesis in chronic schizophrenia. Clinical ineffectiveness of metyrosine.
Arch Gen Psychiatry. 1977 Jun;34(6):649-55.
- PubMed ID
- 17374 [ View in PubMed]
- Abstract
According to the dopamine (DA) hypothesis of schizophrenia, there is a functional excess of dopaminergic activity within unspecified areas of the brain in schizophrenic patients. As a clinical test of this hypothesis, we administered metyrosine for three weeks to symptomatic chronic male schizophrenic patients who were maintained on suboptimal doses of neuroleptic agents. Metyrosine inhibits tyrosine hydroxylase, the rate-limiting enzymatic step in the synthesis of DA. No clinical improvement was observed, using the National Institute of Mental Health Inpatient Behavioral Rating Scale or the Brief Psychiatric Rating Scale. Central inhibition of DA synthesis by metyrosine was suggested, however, by (1) the development of extrapyramidal side effects and (2) a significant increase in plasma prolactin concentrations. Plasma chlorpromazine concentrations remained unchanged during metyrosine treatment. There was, nevertheless, a significant improvement on the scores of the Wechsler Adult Intelligence Scale Comprehension subtest, which measures judgment and common sense. This finding suggests that DA may be involved in the regulation of subtle psychological processes. The results are discussed in light of the DA hypothesis of schizophrenia and previous reports suggesting that metyrosine potentiates the antipsychotic effect of neuroleptics in schizophrenia.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Metyrosine Tyrosine 3-monooxygenase Protein Humans YesBinderDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareCitalopramMetyrosine The risk or severity of extrapyramidal symptoms can be increased when Metyrosine is combined with Citalopram. DesvenlafaxineMetyrosine The risk or severity of extrapyramidal symptoms can be increased when Metyrosine is combined with Desvenlafaxine. DuloxetineMetyrosine The risk or severity of extrapyramidal symptoms can be increased when Metyrosine is combined with Duloxetine. EscitalopramMetyrosine The risk or severity of extrapyramidal symptoms can be increased when Metyrosine is combined with Escitalopram. FluoxetineMetyrosine The risk or severity of extrapyramidal symptoms can be increased when Metyrosine is combined with Fluoxetine.