Premium
N ‐Methyl‐ d ‐Aspartate‐ or Glutamate‐Mediated Toxicity in Cultured Rat Cortical Neurons Is Antagonized by FPL 15896AR
Author(s) -
Black Marsha A.,
Tremblay Roger,
Mealing Geoff,
Ray Ranjit,
Durkin Jon P.,
Whitfield James F.,
Blosser James,
Morley Paul
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.65052170.x
Subject(s) - nmda receptor , glutamate receptor , neurotoxicity , neuroprotection , antagonist , pharmacology , cortical neurons , chemistry , biology , toxicity , neuroscience , biochemistry , receptor , medicine
The neuroprotective action of ( S )‐α‐phenyl‐2‐pyridineethanamine dihydrochloride (FPL 15896AR), a novel noncompetitive N ‐methyl‐ d ‐aspartate (NMDA) receptor antagonist, was examined in primary rat cortical neuronal cultures. Exposure of cortical cultures to NMDA (50 µ M ) or glutamate (50 µ M ) for 15 min resulted in the death of 85–95% of the neurons during the next 24 h. This neurotoxicity was completely eliminated by adding FPL 15896AR (50 µ M ) to the cultures during the time of NMDA or glutamate exposure. Neuroprotective concentrations of FPL 15896AR also inhibited other acute effects of NMDA. FPL 15896AR (50 µ M ) prevented the loss of membrane‐associated protein kinase C activity that developed by 4 h after transient exposure to 50 µ M NMDA or 50 µ M glutamate. FPL 15896AR also reduced by ∼35% the magnitude of NMDA‐triggered increases in intracellular free Ca 2+ concentration in the cortical cultures. These data indicate that NMDA‐mediated toxicity in cultured cortical neurons can be blocked by the NMDA antagonist FPL 15896AR.