Action of mianserin and zimelidine on the norepinephrine receptor coupled adenylate cyclase system in brain: Subsensitivity without reduction in β-adrenergic receptor binding

R. Mishra, A. Janowsky, F. Sulser

Research output: Contribution to journalArticle

158 Scopus citations

Abstract

The present experiments were undertaken to ascertain whether non-tricyclic, clinically effective, antidepressant drugs such as the tetracyclic mianserin and the serotonin uptake inhibitor, zimelidine, cause alterations of central noradrenergic receptor systems similar to those elicited by classical tricyclic antidepressants, MAO inhibitors and ECT. Like desipramine (DMI), mianserin and zimelidine caused, after chronic administration, a significant reduction in the sensitivity of the cyclic AMP response to (R)-norepinephrine while a single dose of the drugs did not affect the neurohormonal response. The basal levels of the nucleotide were not changed by the antidepressant drugs following acute or chronic administration. While the noradrenergic subsensitivity caused by DMI was linked to a reduction in the Bmax value of 3H-dihydroalprenolol binding, the subsensitivity caused by mianserin and zimelidine was not associated with a decreased density of β-adrenergic receptors. In accord with these data on β-adrenergic receptor binding, the responsivenss of the adrenergic cyclic AMP generating system to the β-adrenergic agonist, (R)-isoproterenol, was significantly reduced following chronic treatment with DMI but not with mianserin or zimelidine. The results provide further evidence for the theory that the delayed therapeutic action of different prototypes of antidepressant treatments may be related to the delayed change in noradrenergic receptor function and that a reduction in the density of β-adrenergic receptors is only one mechanism by which the sensitivity of the system is regulated.

Original languageEnglish (US)
Pages (from-to)983-987
Number of pages5
JournalNeuropharmacology
Volume19
Issue number10
DOIs
StatePublished - 1980

Keywords

  • cyclic AMP
  • desipramine
  • isoproterenol
  • mianserin
  • norepinephrine
  • zimelidine
  • β-receptors

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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