Neurotoxic potential of three structural analogs of β-N-oxalyl-α,β- diaminopropanoic acid (β-ODAP)

Irina A. Omelchenko, Renu K. Jain, Mohammed A. Junaid, S. L.N. Rao, Charles N. Allen

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Lathyrism is a non-progressive motor neuron disease produced by consumption of the excitatory amino acid, 3-N-oxalyl-L-2,3-diaminopropanoic acid (β-ODAP). To learn more about the mechanisms underlying Lathyrism three structural analogs of β-ODAP were synthesized. Carboxymethyl-α,β- diaminopropanoic acid (CMDAP) evoked inward currents which were antagonized by APV (30 μM), but not by CNQX (10 μM). N-acetyl-α,β-diaminopropanoic acid (ADAP) evoked no detectable ionic currents but potentiated N-methyl-D- aspartate (NMDA)-activated currents. The potentiation of NMDA currents by ADAP was blocked by 7-chlorokynurenic acid. Carboxymethylcysteine (CMC) did not activate any detectable ionic currents. None of the three β-ODAP analogs produced visible symptoms of toxicity in day old chicks when administered for 2-3 consecutive days. Ligand binding studies demonstrated that all the three compounds were effective to in displacing [3H]glutamate. The maximum inhibition was 92% for CMDAP, 61% for ADAP, 65% for CMC and 99% for β-ODAP. These data indicate that analogs of β-ODAP may interact with glutamate receptors without producing neurotoxicity.

Original languageEnglish (US)
Pages (from-to)791-797
Number of pages7
JournalNeurochemical Research
Volume24
Issue number6
DOIs
StatePublished - Jun 21 1999

Keywords

  • Excitotoxicity
  • Glutamate
  • Lathyrism
  • NMDA receptor
  • Strychnine-insensitive glycine receptor
  • β-N-oxalyl-α,β-diaminopropanoic acid

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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