• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

1993 Fiscal Year Final Research Report Summary

Study on enhancement of neuronal calcium channel activities by nootropic agents

Research Project

Project/Area Number 04807013
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field General pharmacology
Research InstitutionTokyo Institute of Psychiatry

Principal Investigator

YOSHII Mitsunobu  Tokyo Institute of Psychiatry, Department of Neurophysiology, Section Director, 神経生理研究部門, 副参事研究員 (60091047)

Project Period (FY) 1992 – 1993
KeywordsNootropics / Nefiracetam / Aniracetam / Calcium channel / Cyclic AMP / G-protein / NG108-15 cell
Research Abstract

Effects of nootropic agents (pyrrolidone derivatives) on neuronal calcium (Ca) channels were studied in NG108-15 cells using the whole-cell patch-clamp technique. Nefiracetam (DM-9384), a newly-developed nootropic agent, increased a high voltage-activated, long-lasting component of Ca channel currents two-fold at a low concentration of 1muM without affecting a low voltage-activated, transient component. The dose-response relationship yielded a bell-shaped curve with a peak at 1 muM.Similar, but less potent effects were observed by other nootropic agents in the sequence of nefiracetam > aniracetam > oxiracetam > piracetam. Dibutyryl cyclic AMP (1 mM), an analogue of cyclic AMP, also enhanced the currents, which were not further increased by nefiracetam, or vice versa. The currents enhanced by nefiracetam were markedly reduced by nifedipine (10 muM), an L-type Ca channel blocker. The remaining N-type currents also showed a slightly increase (up to 1.5-fold). These facilitatory actions of nefiracetam were prevented by the non-specific protein kinase inhibitor, H-7 (100 muM). Cells treated with pertussis toxin (500 ng/ml, >20 h) to inactivate inhibitory G-proteins (Go/Gi) were apparently insensitive to nefiracetam. The results suggest that the nootropic agents may enhance the activity of neuronal L-type Ca channels under the regulation of inhibitory G-proteins and possibly, cyclic AMP-dependent processes.

  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Yoshii,M.: "Enhancement of neuronal calcium channel currents by the nootropic agent,nefiracetam(DM-9384),in NG108-15 cells." Brain Research. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 渡部繁男: "イオンチャンネルと抗痴呆薬" 神経精神薬理. 15. 227-235 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshii,M.: "Interaction between enkephalin and nefiracetam(DM-9384),a nootropic agent,observed in calcium channel currents and cAMP in NG108-15 cells." Soc.Neurosci.Abstr.19. 1126 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshii,M.: "Mechanisms of the facilitatory action of nootropics on high voltage-activated calcium channels in NG108-15 cells." Jpn.J.Physiol.43,Suppl.2. 43. S175 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watabe,S.: "DM-9384,a nootropic agent,interferes with the inhibitory action of opiates on N-type calcium channels in NG108-15 cells." Soc.Neurosci.Abstr.18. 434 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshii,M.: "Site of action of cognitive enhancer DM-9384 that enhances long-lasting calcium channel currents in NG108-15 cells." Soc.Neurosci.Abstr.18. 435 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watabe S.: "Ion channels and cognitive enhancers." Japan J.Psychopharmacol. 15. 227-235 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshii M.: "Enhancement of neuronal calcium channel currents by the nootropic agent, nefiracetam (DM-9384), in NG108-15 cells." Brain Res.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshii M.: "Site of action of cognitive enhancer DM-9384 that enhances long-lasting calcium channel currents in NG108-15 cells." Soc.Neurosci.Abstr.18. 435 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watabe S.: "DM-9383, a nootropic agent, interferes with the inhibitory action of opiates on N-type calcium channels in NG108-15 cells." Soc.Neurosci.Abstr.18. 434 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watabe S.: "Site of action of the new cognitive enhancer, DM-9384, which enhances calcium channel currents in NG108-15 cells." Japan J.Pharmacol.61. 253P (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshii M.: "Mechanisms of the facilitatory action of nootropics on high voltage-activated calcium channels in NG108-15 cells." Jpn.J.Physiol.43, Suppl.2. 175 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshii M.: "Interaction between enkephalin and nefiracetam (DM-9384), a nootropic agent, observed in calcium channel currents and cAMP in NG108-15 cells." Soc.Neurosci.Abstr.19. 1126 (1993)

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 1995-03-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi