L-trans-Pyrrolidine-2,4-dicarboxylic acid (L-trans-PDC) is a glutamate uptake blocker, serving as a "conformer mimic" of the glutamate molecule as recognized by EAAT (excitatory amino acid transporter) proteins. L-trans-PDC is demonstrated to increase extracellular glutamate concentration without affecting extracellular GABA levels. Blockade of glutamate uptake by L-trans-PDC has a correlated effect of inducing neuronal Ca2+ influx and massive NMDA receptor-mediated neuronal death. Specificity of L-trans-PDC for the EAAT protein over other glutamate-recognizing loci indicates a particular structural requirement for the EAAT binding site, satisfied by this structurally rigid pyrrolidine "conformer mimic" of glutamate. L-trans-Pyrrolidine-2,4-dicarboxylic acid is an inhibitor of EAAT1, EAAT2, EAAT3, EAAT4 and EAAT5.
