Effects of GYKI 52466 and some 2,3-benzodiazepine derivatives on hippocampal in vitro basal neuronal excitability and 4-aminopyridine epileptic activity

In order to determine whether the anticonvulsant effect of 2,3-benzodiazepi nes is also displayed in a model of in vitro epilepsy, such as the ''epilep tiform' hippocampal slice, we studied the effects of 2,3-benzodiazepine 1-( 4-aminophenyl)-1-methyl-7,8-methylenedioxe- 5H 2,3-benzadiazepine hydrochlo ride (GYKI 52466) and some new 2,3-benzodiazepine derivatives on CA1 basal neuronal excitability and on CAI epileptiform burst activity produced by 4- aminopyridine in rat hippocampal slices. The results showed that GYKI 52466 affected basal neuronal excitability as evidenced by its influence on the magnitude of the CAI orthodromic-evoked field potentials. 2,3-Benzodiazepin es showed their antiepileptic effect also in an in vitro model of experimen tal epilepsy. The effects of the new 2,3-benzodiazepine derivatives suggest that the methylenedioxidation in positions 7 and 8 of the 2,3-benzodiazepi ne ring is the main structural modification for the antiepileptic effect of 2,3-benzodiazepines to take place. (C) 2000 Published by Elsevier Science B.V. All rights reserved.