Epileptiform discharges induced by combined application of bicuculline and 4-aminopyridine are resistant to standard anticonvulsants in slices of rats.

Application of 4-aminopyridine (4AP) has previously been reported to produce different patterns of epileptiform discharges in entorhinal cortex-hippocampal-slices. Here we describe that 4-AP induced epileptiform activity in the EC becomes insensitive to anticonvulsant drugs (phenytoin, carbamazepine, valproic acid, phenobarbital) when GABAergic transmission is blocked by bicuculline. We propose that the activities induced by 4-aminopyridine and bicuculline may provide an in vitro model for the development of new drugs against difficult-to-treat focal epilepsy.