The effect of clozapine on plasma norepinephrine: Relationship to clinical efficacy

Alan Breier, Robert W. Buchanan, Royce W. Waltrip, Samuel Listwak, Courtney Holmes, David S. Goldstein

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Clozapine is an atypical neuroleptic medication with superior efficacy to conventional antipsychotic agents for patients with chronic, symptomatic schizophrenia. Neurochemical characteristics that distinguish clozapine from other neuroleptics and contribute to its differential efficacy are not known. We assessed the effects of clozapine on plasma levels of norepinephrine (NE) in a double-blind, parallel groups comparison of clozapine (n = 11) and haloperidol (n = 15) in chronic schizophrenic outpatients who had been previously treated with fluphenazine. Simultaneous measurements were obtained for plasma levels of the catecholamine precursor dopa, the dopmaine metabolite dihydroxyphenylacetic acid (DOPAC), the NE metabolite 3,4-dihydroxyphenylglycol (DHPG), adrenocorticotropin (ACTH), cortisol, and hemodynamic parameters. Clozapine produced marked increases (471%) in plasma NE levels, whereas haloperidol had no significant effects on plasma NE levels. Clozapine also increased dopa and tended to increase DOPAC levels, without effects on DHPG, ACTH, or cortisol levels and without consistent changes in blood pressure. Across patients, the magnitude of clozapine-induced increments in plasma NE levels was positively related to improvement in positive symptoms and global symptomatology and was unrelated to the occurrence of extrapyramidal symptoms. The results suggest that clozapine differs importantly from other neuroleptics in increasing plasma NE levels, with the peripheral noradrenergic stimulation related to its superior efficacy profile. The unchanged DHPG levels and absence of hypertension suggest a more complex mechanism of action of clozapine than heightened NE release alone.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalNeuropsychopharmacology
Volume10
Issue number1
StatePublished - 1994
Externally publishedYes

Fingerprint

Clozapine
Norepinephrine
Antipsychotic Agents
Adrenocorticotropic Hormone
Dihydroxyphenylalanine
Haloperidol
Hydrocortisone
Fluphenazine
Acids
Catecholamines
Schizophrenia
Outpatients
Hemodynamics
Blood Pressure
Hypertension

Keywords

  • α-receptor, mechanism of action
  • catecholamines
  • clinical efficacy
  • clozapine
  • plasma norepinephrine
  • schizophrenia

ASJC Scopus subject areas

  • Pharmacology

Cite this

Breier, A., Buchanan, R. W., Waltrip, R. W., Listwak, S., Holmes, C., & Goldstein, D. S. (1994). The effect of clozapine on plasma norepinephrine: Relationship to clinical efficacy. Neuropsychopharmacology, 10(1), 1-7.

The effect of clozapine on plasma norepinephrine : Relationship to clinical efficacy. / Breier, Alan; Buchanan, Robert W.; Waltrip, Royce W.; Listwak, Samuel; Holmes, Courtney; Goldstein, David S.

In: Neuropsychopharmacology, Vol. 10, No. 1, 1994, p. 1-7.

Research output: Contribution to journalArticle

Breier, A, Buchanan, RW, Waltrip, RW, Listwak, S, Holmes, C & Goldstein, DS 1994, 'The effect of clozapine on plasma norepinephrine: Relationship to clinical efficacy', Neuropsychopharmacology, vol. 10, no. 1, pp. 1-7.
Breier A, Buchanan RW, Waltrip RW, Listwak S, Holmes C, Goldstein DS. The effect of clozapine on plasma norepinephrine: Relationship to clinical efficacy. Neuropsychopharmacology. 1994;10(1):1-7.
Breier, Alan ; Buchanan, Robert W. ; Waltrip, Royce W. ; Listwak, Samuel ; Holmes, Courtney ; Goldstein, David S. / The effect of clozapine on plasma norepinephrine : Relationship to clinical efficacy. In: Neuropsychopharmacology. 1994 ; Vol. 10, No. 1. pp. 1-7.
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