Novel glutamate receptor antagonists selectively protect against kainic acid neurotoxicity in cultured cerebral cortex neurons

J Neurochem. 1990 Nov;55(5):1821-3. doi: 10.1111/j.1471-4159.1990.tb04976.x.

Abstract

The effect on excitatory amino acid (EAA)-induced toxicity of two novel non-N-methyl-D-aspartate (non-NMDA) antagonists 2-amino-3-[3-(carboxymethoxy)-5-methylisoxazol-4-yl]propionic acid (AMOA) and 2-amino-3-[2-(3-hydroxy-5-methyl-isoxazol-4-yl)methyl-5-methyl-3- oxoisoxazolin-4-yl]propionic acid (AMNH) was tested in primary cultures of cerebral cortex neurons. Such cultures provide a useful model for the investigation of the toxicity of EAAs and a convenient screening system for potential neuroprotective activity of pharmacological agents. It was demonstrated that AMNH and AMOA abolished neurotoxicity induced by kainic acid with IC50 values of 62 +/- 10 and 120 +/- 19 microM, respectively. No effect on neuronal damage induced by NMDA or AMPA could be detected.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects*
  • Excitatory Amino Acid Antagonists*
  • Glutamic Acid
  • Isoxazoles / pharmacology*
  • Kainic Acid / poisoning*
  • Neurons / drug effects*
  • Propionates / pharmacology*
  • Receptors, Glutamate
  • Receptors, Neurotransmitter / physiology*

Substances

  • Excitatory Amino Acid Antagonists
  • Isoxazoles
  • Propionates
  • Receptors, Glutamate
  • Receptors, Neurotransmitter
  • 2-amino-3-(3-(carboxymethoxy)-5-methylisoxazol-4-yl)propionic acid
  • 2-amino-3-(2-(3-hydroxy-5-methylisoxazol-4-yl)methyl-5-methyl-3-oxoisoxazolin-4-yl)propionic acid
  • Glutamic Acid
  • Kainic Acid