Neuroleptic‐potentiating effect of α‐methyl‐p‐tyrosine compared with haloperidol and placebo in a double‐blind cross‐over trial

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Abstract
The hypothesis that schizophrenia results from overactive dopaminergic influences suggests that reducing dopamine synthesis may increase the clinical effects of dopamine receptor blocking neuroleptic drugs. The neuroleptic potentiating role of .alpha.-methyl-p-tyrosine (AMPT), a tyrosine hydroxylase inhibitor, was compared with haloperidol and placebo in a double-blind cross-over trial. Both AMPT and haloperidol increased the anti-schizophrenic effect of neuroleptic treatment in reduced dose compared with placebo (P < 0.05), though 2 patients relapsed during the AMPT period. Both drugs slightly increased extrapyramidal symptoms, but the effect was greater with haloperidol. The limited antipsychotic effect and the potential for aggravating neurological symptoms suggest that the combination of AMPT and neuroleptics does not offer a superior advantage to treating schizophrenia. AMPT may be useful as a research tool in elucidating pathogenetic mechanisms.