Neurotoxic potential of three structural analogs of beta-N-oxalyl-alpha,beta-diaminopropanoic acid (beta-ODAP)

Lathyrism is a non-progressive motor neuron disease produced by consumption of the excitatory amino acid, 3-N-oxalyl-L-2,3-diaminopropanoic acid (beta -ODAP). To learn more about the mechanisms underlying Lathyrism three struc tural analogs of beta-ODAP were synthesized. Carboxymethyl-alpha,beta-diami nopropanoic acid (CMDAP) evoked inward currents which were antagonized by A PV (30 mu M), but not by CNQX (10 CIM) N-acetyl-alpha,beta-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 beta-ODAP an alogs produced visible symptoms of toxicity in day old chicks when administ ered for 2-3 consecutive days. Ligand binding studies demonstrated that all the three compounds were effective to in displacing [H-3]glutamate. The ma ximum inhibition was 92% for CMDAP, 61% for ADAP, 65% for CMC and 99% for b eta-ODAP. These data indicate that analogs of beta-ODAP may interact with g lutamate receptors without producing neurotoxicity.