Inhibitory effects of antidepressants on NMDA-induced currents in Xenopus oocytes injected with rat brain RNA

Michihisa Tohda, Hisashi Urushihara, Yasuyuki Nomura

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Although it has been reported that desipramine affects ion-channel activity of NMDA receptor/ion-channel complexes, the binding sites remain unclear. To identify the binding site, influences of desipramine on NMDA-induced current were examined in Xenopus oocytes injected with rat brain RNA and compared with those of blockers, MK-801, Zn2+ and Mg2+. Application of 100 μM desipramine irreversibly inhibited NMDA-induced inward current as well as 1 μM MK-801. Mg2+ and Zn2+ showed a reversible inhibition. Pretreatment with Mg2+ or Zn2+ abolished the irreversible inhibition of desipramine. In contrast, the irreversible inhibition of desipramine was still observed after application of Mg2+ and Zn2+. These results suggest that Mg2+/Zn2+ and desipramine bind on different sites from each other and affect the cation permeability via different mechanisms. Regarding inhibitory effects of other antidepressant drugs, imipramine and setiptiline were found to markedly inhibit NMDA current, while maprotiline, amitriptyline and lofepramine slightly inhibited the current. Mianserin, a potent antagonist of 5-HT1c receptors, however, had no influence.

Original languageEnglish
Pages (from-to)53-58
Number of pages6
JournalNeurochemistry International
Volume26
Issue number1
DOIs
Publication statusPublished - 1995
Externally publishedYes

Fingerprint

Desipramine
N-Methylaspartate
Xenopus
Antidepressive Agents
Oocytes
RNA
Brain
Dizocilpine Maleate
Ion Channels
Lofepramine
Binding Sites
Maprotiline
Mianserin
Amitriptyline
Imipramine
N-Methyl-D-Aspartate Receptors
Cations
Permeability

ASJC Scopus subject areas

  • Cell Biology
  • Cellular and Molecular Neuroscience
  • Molecular Biology

Cite this

Inhibitory effects of antidepressants on NMDA-induced currents in Xenopus oocytes injected with rat brain RNA. / Tohda, Michihisa; Urushihara, Hisashi; Nomura, Yasuyuki.

In: Neurochemistry International, Vol. 26, No. 1, 1995, p. 53-58.

Research output: Contribution to journalArticle

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