The glycine binding site of the NMDA receptor: involvement in neurodegeneration and new approach for neuroprotection.
Excitatory amino acids may have a neurotoxic effect in acute and chronic neurodegenerative diseases. Glutamate mediated Ca-influx into the cell is caused by activation of the NMDA-receptor. In addition to the competitive binding site there is a glycine binding site at the NMDA-receptor, where in an agonistic function glycine leads to opening of the ion channel. Antagonists at this glycine binding site may reduce the Ca-influx and thereby have a neuroprotective effect. The affinity of HA-966 to the glycine binding site in human hippocampus brain tissue is in the low micromolar range (Ki = 8.1 +/- 1.5 microM). So HA-966 may play a role as a neuroprotective substance.
Hartmann
J
J
Department of Neurology, Regional Hospital, Offenburg, Federal Republic of Germany.
Ransmayr
G
G
Riederer
P
P
D001345:Autoradiography; D001665:Binding Sites; D001667:Binding, Competitive; D005998:Glycine / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D009410:Nerve Degeneration / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D018696:Neuroprotective Agents; D011760:Pyrrolidinones; D016194:Receptors, N-Methyl-D-Aspartate; C001369:1-hydroxy-3-amino-2-pyrrolidone; D005998:Glycine