GYKI 52466 [1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-
benzodiazepine], a non-competitive
AMPA [alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate] and
kainate receptor antagonist and its two analogues,
GYKI 53405 [1-(4-aminophenyl)-3-acetyl-4-methyl-3,4-dihydro-7,8-methylenedioxy-5H-2,3-
benzodiazepine] and
GYKI 53655 [1-(4-aminophenyl)-3-methylcarbamyl-4-methyl-3,4-dihydro-7,8-methylenedioxy-5H-2,3-
benzodiazepine] were investigated in two seizure models and in
MgCl2 induced global cerebral ischaemia, as an acute neuroprotective model. The ED(50) values of
GYKI 52466 for suppression of the tonic and clonic phases of sound-induced
seizures were 3.6 and 4.3 mg/kg, respectively. The corresponding data for
GYKI 53405 were 1.1 and 3.1 mg/kg, while ED(50) values of
GYKI 53655 were 1.3 and 2.0 mg/kg, respectively. The inhibition of seizure evoked by maximal electroshock was also found to be remarkable: the ED(50) values of
GYKI 52466 and its two analogues were 6.9, 2.6, and 2.2 mg/kg, respectively. All compounds prolonged the survival times in
MgCl2 induced global cerebral ischaemia test in a dose-dependent fashion, with PD(50) (dose of 50% prolongation) values of 24.1, 8.3, and 8.2 mg/kg intraperitoneal, respectively. In audiogenic seizure model the duration of
anticonvulsant action of 10 mg/kg
GYKI 52466 and 5 mg/kg
GYKI 53405,
GYKI 53655 were examined, too. The effect of
GYKI 52466 decreased to 50% after 2 h, while the analogues showed more than 80% seizure suppression 3 h
after treatment. After 6 h the effect of
GYKI 53655 decreased to zero, while the effect of
GYKI 52466, remained on the 50% level.