Abstract
The purpose of this study was to evaluate the hypothesis that neuroleptic non-response in the face of "adequate" DA post-synaptic receptor blockade reflects failure of regulatory mechanisms to decrease DA pre-synaptic activity. Eight chronic schizophrenics, meeting rigorous criteria for neuroleptic non-response, were treated for four weeks with alpha-methylparatyrosine as an adjunct to their previously stable neuroleptic dose. Treatment with AMPT produced a prompt decrease in plasma HVA that was, on average, 72% lower at the end of the study. While there was also strong clinical evidence of reduction in central dopaminergic activity (both a significant reduction in dyskinetic movements and increase in extrapyramidal symptoms), there was virtually no change in severity of psychotic symptoms. Thus, in this group of non-responders, psychotic symptoms persisted despite both extensive dopamine post-synaptic receptor blockade and marked reduction of presynaptic activity. These symptoms may not be directly DA dependent.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Antipsychotic Agents / adverse effects
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Antipsychotic Agents / pharmacology
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Antipsychotic Agents / therapeutic use
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Basal Ganglia Diseases / chemically induced
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Dopamine / biosynthesis
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Dopamine / physiology*
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Drug Resistance
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Drug Synergism
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Frontal Lobe / physiopathology
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Homovanillic Acid / blood
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Humans
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Male
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Methyltyrosines / pharmacology
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Methyltyrosines / therapeutic use*
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Middle Aged
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Nerve Tissue Proteins / antagonists & inhibitors
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Receptors, Dopamine / drug effects
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Receptors, Dopamine / physiology
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Schizophrenia / blood
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Schizophrenia / drug therapy*
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Schizophrenia / physiopathology
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Schizophrenic Psychology*
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Severity of Illness Index
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Treatment Failure
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Tyrosine 3-Monooxygenase / antagonists & inhibitors
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alpha-Methyltyrosine
Substances
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Antipsychotic Agents
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Methyltyrosines
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Nerve Tissue Proteins
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Receptors, Dopamine
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alpha-Methyltyrosine
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Tyrosine 3-Monooxygenase
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Dopamine
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Homovanillic Acid