Quinolinic Acid and Kynurenic Acid in the Mammalian Brain

Abstract

Over the last decade, the study of neuroexcitatory amino acids has become one of the most rapidly expanding areas of neuroscientific research. Interest in this class of compounds was precipitated mainly by the realization that metabolites such as glutamate and aspartate are major neurotransmitters in the central nervous system (Fonnum, 1984; Erecinska and Silver, 1990). However, it is now clear that excitatory amino acids not only play a significant role in a wide array of brain processes such as synaptic plasticity and motor control but may also, as “excitotoxins”, be causally involved in the pathogenesis of various neuro-psychiatric diseases (Cavalheiro et al., 1988). Thus, the pathological overstimulation of excitatory amino acid receptors situated in the neuronal membrane is now believed to result in neurodegeneration in cerebral hypoxia/ischemia, temporal lobe epilepsy and several other diseases including chronic neurodegenerative disorders such as Huntington’s disease (HD) (Schwarcz et al., 1984; Schwarcz and Meldrum, 1985; Rothman and Olney, 1986; Choi, 1988). Pharmacological probes have been used to subdivide the receptors which mediate excitotoxic insults. These receptor are linked to ion channels and are named after their model agonists N-methyl-D-aspartate (NMDA), kainate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) (Watkins et al., 1990).