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

• Published in: European journal of pharmacology Vol. 333; no. 1; pp. 17 - 26
• Main Authors: KUBOVA, H, VILAGI, I, MIKULECKA, A, MARES, P
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 20.08.1997; Elsevier
• Subjects: Animals; Anti-Anxiety Agents; Anticonvulsant action; Anticonvulsants. Antiepileptics. Antiparkinson agents; Benzodiazepines - pharmacology; Biological and medical sciences; Cerebral Cortex - drug effects; Electric Stimulation; Electrodes, Implanted; Electroencephalography - drug effects; Electrophysiology; Epilepsy - physiopathology; Epilepsy, Tonic-Clonic - chemically induced; Epilepsy, Tonic-Clonic - physiopathology; Excitatory Amino Acid Antagonists - pharmacology; Excitatory amino acids; Female; Flumazenil; GYKI 52466; Humans; Male; Medical sciences; Motor Skills - drug effects; Motor system; Neuropharmacology; Pharmacology. Drug treatments; Postural Balance - drug effects; Rats; Rats, Wistar; Receptors, AMPA - antagonists & inhibitors; Excitatory amino acids; GYKI 52466; Anticonvulsant action; Flumazenil; Motor system; Nervous system diseases; Rat; Epilepsy; Rodentia; Variations; Anticonvulsant; Glutamate receptor; Cerebral disorder; Vertebrata; Chemotherapy; Experimental disease; AMPA receptor; Mammalia; Treatment; Convulsion; Animal; Central nervous system disease; Antagonist; Neurological disorder; Mechanism of action; Age
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(97)01119-9

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.