Effects of remacemide and its metabolite FPL 12495 on spike-wave discharges, electroencephalogram and behaviour in rats with absence epilepsy

The effects of the anti-convulsant drug remacemide and one of its active metabolites FPL 12495 were examined in a genetic model for generalized absence epilepsy, the WAG/Rij strain of rats. Number, mean and total duration of spike-wave discharges were measured following oral administration of remacemide and FPL 12495, together with parameters of background electroencephalographic activity (EEG) and spontaneous behaviour in the recording cage. A decrease in the number of the spike-wave discharges was found after remacemide administration. At the highest dose there was near total suppression of the spike-wave discharges. There were no important effects on behaviour and on spectral content of the background EEG, suggesting that remacemide has little side effects. A decrease in the number of spike-wave discharges was also found after FPL 12495 gavage and there was a prolongation of the mean duration. Behavioural changes were only noticed after the highest dose. These were accompanied by changes in the spectral content and particularly by an increase in the amplitude of the delta and the high beta frequencies, together with a decrease in the spindle frequency range. FPL 12495 appeared to be more potent that remacemide in all its effects. The effects of mainly FPL 12495 are uncommon in the sense that so far no other investigated drug shows a decrease in the number together with an increase in the mean duration of the discharges. It seems that in contrast to other anti-epileptic drugs, FPL 12495 exerts a differential action on the two commonly distinguished mechanisms controlling number and duration