Developmental aspects of NMDA receptor agonists and antagonists in the central nervous system

Electrophysiologic responses to the glutamate agonist analogue N-methyl- D-aspartate (NMDA) are enhanced in the developing nervous system compared to responses in the adult. Neurotoxicity mediated by comparable amounts of NMDA and its endogenous analogue quinolinate is more than 50 times greater in the 7-day-old rat brain than in the adult. NMDA antagonist drugs reduce this neurotoxicity with the same spectrum of activity with which they prevent injury from hypoxic-ischemic damage. The greater vulnerability of the immature brain to NMDA mediated injury is probably related to the enhanced role that NMDA mechanisms play in long-term potentiation and activity- dependent plasticity during development.