Endogenous Excitotoxic Agents

Although glutamate and aspartate are among the most likely compounds to function as central neurotransmitters, and both can produce cell death in neonatal animals, the efficient uptake systems for these amino acids mean that exceptionally high concentrations are required for toxicity in adults. A better candidate for an endogenous neurotoxin is quinolinic acid, which produces cell death via activation of the N-methyl-aspartate receptors. Several differences of detail between the activity of quinolinate and N-methyl-aspartate may indicate the existence of subpopulations of the N-methyl-aspartate receptor. Another compound in the same 'kynurenine' pathway as quinolinate, kynurenic acid, is an antagonist of the excitatory and neurotoxic actions of quinolinate, and the overall excitability of the central nervous system and the occurrence of cell death may therefore result from a balance between the concentrations of quinolinate and kynurenate.