Mechanism of peripheral noradrenergic stimulation by clozapine

Igor Elman, David S. Goldstein, Graeme Eisenhofer, Joan Folio, Anil K. Malhotra, Caleb M. Adler, David Pickar, Alan Breier

Research output: Contribution to journalArticle

44 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)29-34
Number of pages6
JournalNeuropsychopharmacology
Volume20
Issue number1
DOIs
StatePublished - Jan 1999
Externally publishedYes

Fingerprint

Clozapine
Norepinephrine
Fluphenazine
Placebos
Catechols
Tritium
Monoamine Oxidase
Intravenous Infusions
Catecholamines

Keywords

  • Catecholamine
  • Clozapine
  • Fluphenazine
  • Norepinephrine
  • Schizophrenia
  • Spillover

ASJC Scopus subject areas

  • Pharmacology

Cite this

Elman, I., Goldstein, D. S., Eisenhofer, G., Folio, J., Malhotra, A. K., Adler, C. M., ... Breier, A. (1999). Mechanism of peripheral noradrenergic stimulation by clozapine. Neuropsychopharmacology, 20(1), 29-34. https://doi.org/10.1016/S0893-133X(98)00047-5

Mechanism of peripheral noradrenergic stimulation by clozapine. / Elman, Igor; Goldstein, David S.; Eisenhofer, Graeme; Folio, Joan; Malhotra, Anil K.; Adler, Caleb M.; Pickar, David; Breier, Alan.

In: Neuropsychopharmacology, Vol. 20, No. 1, 01.1999, p. 29-34.

Research output: Contribution to journalArticle

Elman, I, Goldstein, DS, Eisenhofer, G, Folio, J, Malhotra, AK, Adler, CM, Pickar, D & Breier, A 1999, 'Mechanism of peripheral noradrenergic stimulation by clozapine', Neuropsychopharmacology, vol. 20, no. 1, pp. 29-34. https://doi.org/10.1016/S0893-133X(98)00047-5
Elman I, Goldstein DS, Eisenhofer G, Folio J, Malhotra AK, Adler CM et al. Mechanism of peripheral noradrenergic stimulation by clozapine. Neuropsychopharmacology. 1999 Jan;20(1):29-34. https://doi.org/10.1016/S0893-133X(98)00047-5
Elman, Igor ; Goldstein, David S. ; Eisenhofer, Graeme ; Folio, Joan ; Malhotra, Anil K. ; Adler, Caleb M. ; Pickar, David ; Breier, Alan. / Mechanism of peripheral noradrenergic stimulation by clozapine. In: Neuropsychopharmacology. 1999 ; Vol. 20, No. 1. pp. 29-34.
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