Protective Effect of MKC-231, a Novel High Affinity Choline Uptake Enhancer, on Glutamate Cytotoxicity in Cultured Cortical Neurons

Jpn J Pharmacol. 1998 Feb;76(2):219-22. doi: 10.1254/jjp.76.219.

Abstract

This study was performed to examine the neuroprotective action of 2-(2-oxopyrrolidin-1-yl)-N-(2,3-dimethyl-5,6,7,8-tetrahydrofuro [2,3-b]quinolin-4-yl)acetoamide (MKC-231), which enhances choline uptake and acetylcholine release in the central nervous system. Glutamate neurotoxicity was assessed with cortical cultures obtained from fetal rats. Exposure of cultures to MKC-231 for 12-24 hr ameliorated glutamate cytotoxicity. MKC-231 reduced cytotoxicity induced by ionomycin, a calcium ionophore, but did not affect the cytotoxicity induced by S-nitrosocysteine, a nitric oxide (NO) donor. These findings suggest that MKC-231 protects against glutamate neurotoxicity by suppressing the NO formation triggered by Ca2+-influx.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / embryology
  • Choline / metabolism
  • Glutamic Acid / pharmacology*
  • Neurons / drug effects*
  • Nootropic Agents / pharmacology*
  • Quinolines / pharmacology*
  • Rats

Substances

  • Nootropic Agents
  • Quinolines
  • Glutamic Acid
  • Choline
  • MKC 231