Non-competitive antagonists of N-methyl-D-aspartate receptors protect cortical and hippocampal cell cultures against glutamate neurotoxicity.

Brief exposure of cortical or hippocampal cell cultures to glutamate (500 microM) resulted in a progressive neuronal necrosis which is maximal 18-24 h later. Pretreatment of the cultures by a phencyclidine derivative: thienylphencyclidine (TCP), or the TCP precursor: GK86, or MK801 protected against glutamate toxicity. Non-competitive antagonists of N-methyl-D-aspartate receptors appear as potent tools for the in vitro protection of neuronal cells against excitatory amino acid toxicity.