GYKI 52466 (1-(4-aminophenyl)-4-methyl-7,8-methylendioxy-5H-2,3-benzo-diaz epi ne), 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.

Institute of Physiology Academy of Sciences of the Czech Republic Videnska Prague

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Epilepsy Research in the Institute of Physiology of the Czech Academy of Sciences in Prague