Protective effect of the metabotropic glutamate receptor agonist, DCG-IV, against excitotoxic neuronal death.

(2S,1'R,2'R,3'R)-2-(2,3-Dicarboxycyclopropyl)glycine (DCG-IV), a potent agonist of subtypes 2 and 3 of metabotropic glutamate receptors (mGluR2 or 3), protected cultured cortical neurons against excitotoxicity induced either by a brief exposure to N-methyl-D-aspartate (NMDA) or a prolonged exposure to kainate. As a neuroprotective agent, DCG-IV was much more potent than the mixed agonists 1S,3R-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) or (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-I), suggesting a neuroprotective role for mGluR2 or 3 against excitotoxic neuronal death.