Brain research bulletin
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Brain research bulletin · Oct 2002
Protective effect of the antiepileptic drug candidate talampanel against AMPA-induced striatal neurotoxicity in neonatal rats.
2,3-Benzodiazepines represent a family of specific, noncompetitive AMPA receptor antagonists with anticonvulsant and neuroprotective properties. In this study, the antiexcitotoxic potency of the clinical antiepileptic drug candidate, talampanel (4 x 2 mg/kg), and that of two related 2,3-benzodiazepines, 5-(4-aminophenyl)-8-methyl-9H-1,3-dioxolo[4,5-h][2,3]-benzodiazepine (GYKI 52466) (4 x 10 mg/kg) and GYKI 53784 (4 x 2 mg/kg), was investigated in 7-day-old rats. The AMPA antagonists were applied in four consecutive i.p. injections at 1-h intervals, the first dosage was given shortly after the intrastriatal injection of (S)-alpha-amino-3-hydroxy-5,7-methylisoxazole-4-propionic acid (AMPA) (2.5 nmol). ⋯ Furthermore, the three compounds attenuated the unilateral AMPA injection-induced turning behavior and seizure-like events. Our present findings are in agreement with those of other investigators who found talampanel neuroprotective in various in vivo experimental models. These data indicate that besides being a promising antiepileptic drug candidate talampanel may have a value in the pharmacotherapy of acute and chronic neurodegenerative diseases, including perinatal ischemia/hypoxia-induced brain injuries, as well.