Effects of remacemide and its metabolite Fpl-12495 on spike-wave discharges, EEG, and behavior in rats with absence epilepsy

Anticonvulsant drugs may or may not be effective against generalized absence epilepsy. Carbamazepine and phenytoin aggravate spike-wave discharges (SWD) whereas valproate and benzodiazepines reduce SWD. The effects of the new anticonvulsant remacemide on SWD are unknown, which prompted us to investigate the effects of remacemide and its active metabolite FPL 12495 in a genetic rat model for absence epilepsy, the WAG/Rij strain. Number and mean duration of SWD, parameters of the background EEG and spontaneous behavior were measured after various oral doses of remacemide and FPL 12495. A decrease in the number of SWD was noted after remacemide administration. At the highest dose, SWD were almost completely suppressed and there were no important effects on behavior or on spectral content of the background EEG, suggesting that remacemide has few side effects and might be effective against absence epilepsy. A decrease in the number of SWD was also noted after FPL 12495 gavage, but mean duration was prolonged. Behavioral changes were apparent only after the highest dose, accompanied by changes in spectral content, suggesting that FPL 12495 has other central effects as well. FPL 12495 appeared to be more potent than remacemide in all its effects. The effects of FPL 12495 are unusual in that no other investigated drug has yet shown a decrease in number together with an increase in mean duration of discharges. FPL 12495 appears to exert a differential action on the two commonly distinguished mechanisms controling number and duration