NON-NMDA RECEPTOR ANTAGONIST GYKI-52466 SUPPRESSES CORTICAL AFTERDISCHARGES IN IMMATURE RATS

GYKI 52466 -methyl-7,8-methylendioxy-5H-2,3-benzo-diazepine), a non-co mpetitive non-NMDA receptor antagonist, was tested against epileptic a fterdischarges elicited by cortical stimulation in 12-, 18- and 25-day -old rats with implanted electrodes. Shortening of afterdischarges and a decrease in intensity of clonic movements accompanying both stimula tion and afterdischarges were induced by the 20 mg/kg dose of GYKI 524 66 in 18- and 25-day-old animals, whereas 12-day-old rat pups exhibite d only shortening of electroencephalographic afterdischarges. The 10 m g/kg dose of GYKI 52466 did not significantly change afterdischarges i n any age group. Motor skills were compromised after the 20 mg/kg dose of GYKI 52466. This effect was again more marked in 18- and 25-day-ol d animals than in the youngest group. In addition, anxiolytic-like act ion was observed in the jumping down test in 25-day-old rats. This eff ect was not influenced by a benzodiazepine antagonist flumazenil. On t he contrary, the anticonvulsant action of GYKI 52466 was partly blocke d by flumazenil, indicating thus multiple mechanisms of action of GYKI 52466. (C) 1997 Elsevier Science B.V.