Pretreatment with L-kynurenine, the precursor to the excitatory amino acid antagonist kynurenic acid, suppresses epileptiform activity in combined entorhinal/hippocampal slices

Neurosci Lett. 1997 Mar 14;224(2):115-8. doi: 10.1016/s0304-3940(97)13472-3.


The kynurenine pathway converts tryptophan into various compounds, including L-kynurenine, which in turn can be converted to the excitatory amino acid receptor antagonist kynurenic acid. The hypothesis that endogenously-produced kynurenic acid could have physiological effects was tested in combined entorhinal/hippocampal slices from adult rats. Specifically, perfusion with L-kynurenine (1 mM) was examined for its ability to suppress epileptiform activity produced by subsequent perfusion with buffer lacking added magnesium (nominal 0 mM magnesium buffer). Importantly, treatment with L-kynurenine did not appear to have depressant effects in itself, but it prevented spontaneous epileptiform activity in all 64 slices subsequently perfused with 0 mM magnesium buffer. In contrast, 45 slices that were not pretreated with L-kynurenine exhibited spontaneous epileptiform activity. These data support the hypothesis that endogenously-produced kynurenic acid can be produced and released in brain slices, where it can suppress excitatory activity in an "anticonvulsant' manner. Therefore, manipulation of the kynurenine pathway might constitute a useful new direction for anticonvulsant drug development.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology
  • Buffers
  • Electrophysiology
  • Entorhinal Cortex / physiopathology*
  • Epilepsy / chemically induced
  • Epilepsy / drug therapy*
  • Excitatory Amino Acid Antagonists / metabolism
  • Female
  • Hippocampus / physiopathology*
  • Kynurenic Acid / metabolism
  • Kynurenine / pharmacology*
  • Magnesium / pharmacology
  • Male
  • Organ Culture Techniques
  • Protein Precursors / pharmacology*
  • Rats
  • Rats, Sprague-Dawley


  • Anticonvulsants
  • Buffers
  • Excitatory Amino Acid Antagonists
  • Protein Precursors
  • Kynurenine
  • Kynurenic Acid
  • Magnesium