• glycine antagonist site;
  • AIDS;
  • N-methyl-d-aspartate;
  • glutamate neurotoxicity;
  • mammalian central neurons;
  • retinal ganglion cells


Prior studies with in vitro model systems have suggested that at least part of the neurological manifestations of AIDS may stem from neuronal injury involving the HIV-1 coat protein gp120. This form of neuronal damage is most probably mediated indirectly by a complex set of cellular interactions among macrophages, astrocytes, and neurons, resulting in a final common pathway of overstimulation of N-methyl-d-aspartate (NMDA) receptors. We studied the neuroprotective effect from gp120-induced neuronal injury of an antagonist of the glycine site of the NMDA receptor, 7-chlorokynurenate. In identified rat retinal ganglion cells in culture, we found that 50 μM 7-chlorokynurenate significantly abrogated the injury engendered by 20 pM gp120. Addition of 300 μM exogenous glycine prevented this protective effect of 50 μM 7-chlorokynurenate. These data suggest that glycine site antagonists of the NMDA receptor may have therapeutic potential for ameliorating neuronal damage associated with gp120.