Non-NMDA receptor antagonist GYKI 52466 suppresses cortical afterdischarges in immature rats

GYKI 52466 (1-(4-aminophenyl)-4-methyl-7,8-methylendioxy-5H-2,3-benzo-diazepine), a non-competitive non-NMDA receptor antagonist, was tested against epileptic afterdischarges 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 stimulation and afterdischarges were induced by the 20 mg/kg dose of GYKI 52466 in 18- and 25-day-old animals, whereas 12-day-old rat pups exhibited only shortening of electroencephalographic afterdischarges. The 10 mg/kg dose of GYKI 52466 did not significantly change afterdischarges in 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-old animals than in the youngest group. In addition, anxiolytic-like action was observed in the jumping down test in 25-day-old rats. This effect was not influenced by a benzodiazepine antagonist flumazenil. On the contrary, the anticonvulsant action of GYKI 52466 was partly blocked by flumazenil, indicating thus multiple mechanisms of action of GYKI 52466.