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-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.
Kubová
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H
Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska, Prague. kubova@biomed.cas.cz
Világi
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Mikulecká
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Mares
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D000818:Animals; D014151:Anti-Anxiety Agents; D001569:Benzodiazepines / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects*; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000187:drug effects; D004594:Electrophysiology; D004827:Epilepsy / Q000503:physiopathology; D004830:Epilepsy, Tonic-Clonic / Q000139:chemically induced / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D009048:Motor Skills / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*
D014151:Anti-Anxiety Agents; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; C061950:GYKI 52466; D001569:Benzodiazepines