Abstract
Elevated plasma norepinephrine (NE) levels is a relatively consistent clinical effect of clozapine. Plasma NE levels reflect an interplay of release, reuptake, metabolism, and excretion. To explore the mechanism of clozapine-induced plasma NE elevation, we measured arterial plasma levels of NE and other catechols during intravenous infusion of tritium-labeled NE (3H-NE) in schizophrenic patients treated with clozapine, fluphenazine, or placebo. Clozapine-treated patients had markedly higher levels of NE than did the patients treated with fluphenazine or placebo. NE spillover averaged more than three times higher in clozapine-treated patients; whereas NE clearance did not differ among the groups. Production of 3H-dihydroxyphenylglycol (3H-DHPG), a purely intraneuronal metabolite of 3H-NE in clozapine-treated patients was normal, indicating that clozapine did not affect neuronal uptake of NE. Because plasma levels of DHPG and dihydroxyphenylacetic acid (DOPAC), deaminated metabolites of catecholamines, in clozapine-treated patients were normal, clozapine also did not seem to inhibit intraneuronal monoamine oxidase (MAO). High plasma NE levels in clozapine-treated patients, therefore, resulted from increased NE spillover rather than decreased reuptake, metabolism, or clearance. Copyright (C) 1999 American College of Neuropsychopharmacology.
Original language | English (US) |
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Pages (from-to) | 29-34 |
Number of pages | 6 |
Journal | Neuropsychopharmacology |
Volume | 20 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1999 |
Externally published | Yes |
Keywords
- Catecholamine
- Clozapine
- Fluphenazine
- Norepinephrine
- Schizophrenia
- Spillover
ASJC Scopus subject areas
- Pharmacology