piperidines and Carbon-Monoxide-Poisoning

Topics: Adolescent; Brain Diseases; Carbon Monoxide Poisoning; Cognition Disorders; Donepezil; Humans; Indans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Nootropic Agents; Piperidines

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.

Topics: Animals; Binding Sites; Carbon Monoxide Poisoning; Dizocilpine Maleate; Glycine; Hippocampus; Male; Mice; Piperidines; Receptors, N-Methyl-D-Aspartate; Vasodilator Agents