Protection against dendrotoxin-induced clonic seizures in mice by anticonvulsant drugs

Various anticonvulsant drugs were evaluated for their ability to protect against clonic seizures induced in mice by intraventricular injection of the K + channel blocking peptide dendrotoxin (DTX). Phenytoin, the phenytoin-like anticonvulsant carbamazepine and the broad spectrum drug valproate were effective in this model, whereas the GABA-enhancers diazepam and tiagabine, the NMDA antagonists (±)-CPP and (+)-MK-801, the AMPA antagonist NBQX, the antiabsence drug ethosuximide and the Ca 2+ channel antagonist nimodipine were inactive. In contrast to the lack of activity of other NMDA antagonists, phencylclidine and ADCI [(±)-aminocarbonyl-10,11-dihydro-5 H-dibenzo [ a,d]cyclohepten-5,10-imine] were potent antagonists of DTX-induced seizures.