Effects of N-methyl-D-aspartate receptor antagonists on carbon monoxide- induced brain damage in mice

H. Ishimaru, A. Katoh, H. Suzuki, T. Fukuta, T. Kameyama, T. Nabeshima

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The mechanism of neurodegeneration and the possible therapeutic amelioration were investigated in a model induced by successive carbon monoxide (CO) exposures. Successive CO exposures resulted in a consistent pattern of degeneration of hippocampal CA1 pyramidal cells, which was quantified using an image analyzer. Competitive and noncompetitive antagonists of N-methyl-D-aspartate (NMDA) receptors, cyclopentenophenanthrene, (+)-5-methyl-10,11-dihydro-5H- dibenzo[a,d]cyclohepten,5,10-imine maleate and an antagonist of glycine binding sites, 7-chlorokynurenic acid, significantly reduced the CO-induced neurodegeneration. Ifenprodil (a antagonist of polyamine binding sites) and glycine had no effect. From these results, it is clear that NMDA receptor/ion channel complex is involved in the mechanism of CO-induced neurodegeneration, and that glycine binding site antagonist as well as NMDA competitive and noncompetitive antagonists may have neuroprotective properties in neurological disorders associated with overactivation of NMDA receptors.

Original languageEnglish
Pages (from-to)349-352
Number of pages4
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number1
Publication statusPublished - 01-01-1992


All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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