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.
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D003986:Dibenzocycloheptenes / Q000494:pharmacology; D016291:Dizocilpine Maleate; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D009498:Neurotoxins / Q000494:pharmacology*; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011355:Prodrugs / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects*
D003986:Dibenzocycloheptenes; D005971:Glutamates; D009498:Neurotoxins; D011355:Prodrugs; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C057667:GK 86; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; C012058:tenocyclidine; D010622:Phencyclidine