Transient up-regulation of gamma-aminobutyric acid(A) receptor binding by lubeluzole after neocortical specify lesion in rats.
The effect of the neuroprotective drug lubeluzole on cortical receptor binding was investigated in animals with photothrombotic ischemic lesions. Control animals were treated with the inactive stereoisomer of the drug. Lubeluzole was applied intravenously as a single bolus (0.31 mg/kg) followed by a 1-h infusion of 0.31 mg/kg. Lubeluzole selectively increased gamma-amino-butyric acid(A) (GABA(A)) receptor binding but had no significant and/or consistent effects on N-methyl-D-aspartate (NMDA), (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), and kainate receptors. Lubeluzole caused a significant up-regulation of GABA(A) receptor binding in the lesioned area as well as in unimpaired cortical areas of both hemispheres. This effect appeared in the hours following the lesion and peaked at 24 h. Our findings suggest that reduced cortical excitability brought about by increased binding capacities of GABA(A) receptors may contribute to the neuroprotective effect of lubeluzole.
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Institute of Medicine, Research Center Juelich, D-52425, Juelich, Germany. m.que@fz-juelich.de
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D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D009118:Muscimol / Q000493:pharmacokinetics; D019579:Neocortex / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010777:Photochemistry / Q000379:methods; D010880:Piperidines / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D012395:Rose Bengal / Q000009:adverse effects; D013844:Thiazoles / Q000494:pharmacology*; D014316:Tritium; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
D009118:Muscimol; D018696:Neuroprotective Agents; D010880:Piperidines; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D012395:Rose Bengal; D013844:Thiazoles; D014316:Tritium; C097722:lubeluzole