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Neurotoxic Potential of Three Structural Analogs of β-N-oxalyl-α,β-Diaminopropanoic Acid (β-ODAP)

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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.

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Author information

Authors and Affiliations

  1. Center for Research on Occupational and Environmental Toxicology, New York

    Irina A. Omelchenko & Charles N. Allen (Ph.D.)

  2. Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, Oregon, 97201-3098

    Charles N. Allen (Ph.D.)

  3. NYS Institute for Basic Research in Developmental Disabilities, New York

    Renu K Jain

  4. Department of Biochemistry, Osmania University, Hyderabad, India

    Mohammed A. Junaid & S.L.N. Rao

Authors
  1. Irina A. Omelchenko
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  2. Renu K Jain
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  3. Mohammed A. Junaid
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  4. S.L.N. Rao
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  5. Charles N. Allen
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Correspondence to Charles N. Allen.

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Omelchenko, I.A., Jain, R.K., Junaid, M.A. et al. Neurotoxic Potential of Three Structural Analogs of β-N-oxalyl-α,β-Diaminopropanoic Acid (β-ODAP). Neurochem Res 24, 791–797 (1999). https://doi.org/10.1023/A:1020791815848

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  • DOI: https://doi.org/10.1023/A:1020791815848

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