LUBELUZOLE BLOCKS INCREASES IN EXTRACELLULAR GLUTAMATE AND TAURINE INTHE PERIINFARCT ZONE IN RATS

A microdialysis probe was positioned inside the peri-infarct zone of a photochemically induced neocortical infarct in rats. Extracellular gl utamate rose within 20 min after the start of infarct induction and co ntinued to increase during the 5 h observation period to 5.5-fold the pre-infarct baseline value of 0.8 +/- 0.4 mu mol/l. Glutamine increase d only 1.4-fold. Changes in peri-infarct glutamate were preceded by st eep rises in taurine (a 3.9-fold increase from the baseline value of 2 .8 +/- 0.7 mu mol/l), which coincided with spreading depressions durin g infarct induction. Post-treatment with lubeluzole (3,4-difluoro-phen oxy)methyl]-1-piperidineethanol, 1.25 mg/kg i.v.), a new cerebroprotec tive drug, blocked the peri-infarct increases of glutamate and taurine , whereas the R-enantiomer was ineffective. Since lubeluzole has previ ously been shown to stereospecifically decrease glutamate-activated ni tric oxide (NO) toxicity in vitro, the present in vivo stereospecific effect of lubeluzole may be related to modulation of the cascade of NO toxicity, thus preventing NO toxicity-mediated increases in extracell ular glutamate. Blockade of the peri-infarct taurine response suggests that lubeluzole also may have reduced cellular osmotic stress in the peri-infarct zone. (C) 1997 Elsevier Science B.V.