N‐Methyl‐d‐Aspartate‐ or Glutamate‐Mediated Toxicity in Cultured Rat Cortical Neurons Is Antagonized by FPL 15896AR

Abstract

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 µM) or glutamate (50 µM) 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 µM) 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 µM) prevented the loss of membrane‐associated protein kinase C activity that developed by 4 h after transient exposure to 50 µM NMDA or 50 µM glutamate. FPL 15896AR also reduced by ∼35% the magnitude of NMDA‐triggered increases in intracellular free Ca2+ 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.

Therapeutic Effects of Coenzyme Q10and Remacemide in Transgenic Mouse Models of Huntington's Disease

“…This may be related to better tolerability and fewer behavioral side effects than those seen with agents such as MK-801, which dissociates from the channel slowly, and may therefore block normal synaptic activity. Remacemide attenuates excitotoxicity in vitro and focal ischemic lesions in vivo (Bannan et al, 1994;Black et al, 1995) and is effective in blocking malonate lesions (Greene et al, 1996). Remacemide has been tolerated well in clinical trials for cerebral ischemia and in HD patients (Kieburtz et al, 1996;Dyker and Lees, 1999).…”

Organotypic Hippocampal Slice Cultures for Studies of Brain Damage, Neuroprotection and Neurorepair

“…This suggests that protection is only effective against mild insults or that hypoxia and OGD in part act through different mechanisms. Blockade of voltage sensitive sodium channels by TTX is neuroprotective both in vivo [148][149][150], in cultured cortical neurons [151] and in hippocampal slice cultures [1].…”

Evaluation of glutathione-sensitive fluorescent dyes in cortical culture

“…Primary cortical neurons from E18 rat fetuses were prepared and cultured on 12-mm glass coverslips (Bellco Glass, Vineland, USA) incubated in 24-well plates (Du Pont-Life Technologies) as described previously (Black et al, 1995). The same procedure was employed for preparation of mouse cultures.…”