Inhibitory effects of antidepressants on NMDA-induced currents in Xenopus oocytes injected with rat brain RNA.
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 microM desipramine irreversibly inhibited NMDA-induced inward current as well as 1 microM 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.
Tohda
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Urushihara
H
H
Nomura
Y
Y
D000818:Animals; D000928:Antidepressive Agents / Q000145:classification / Q000494:pharmacology*; D001923:Brain Chemistry; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005998:Glycine / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008845:Microinjections; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000008:administration & dosage / Q000235:genetics*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D014982:Xenopus laevis; D015032:Zinc / Q000494:pharmacology
D000928:Antidepressive Agents; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D008274:Magnesium; D015032:Zinc; D005998:Glycine