Interaction of flunarizine with sodium valproate or ethosuximide in gamahydroxybutyrate induced absence seizures in rats

Sodium valproate(VPA), ethosuximide(ESM), 200 mg/kg ip and flunarizine (FLU) 5 or 10 mg/kg ip were first administered independently to rats in order to study their effects on behavioural and EEG aspects of spike and wave discharges (SWDs) induced by γ- hydroxybutyrate (GHB,100 mg/kg ip). GHB treated rats show behavioural changes and concomitant repetitive EEG episodes of 7 to 9 Hz SWDs, mimicking human absence seizures (AS), and can be used as a pharmacological model. The number and duration of SWDs were calculated for 1 hr from the EEG and were parameters for drug evaluation. VPA and ESM at 200 mg/kg, significantly reduced SWD number and duration/hr, while FLU showed significant reduction only at 10 but not at 5 mg/kg. Combination of FLU, 10 mg/kg with either VPA or ESM showed significant reduction of SWD number and duration, suggesting an additive effect of the anti-absence agents with the calcium channel blocker, FLU, on experimental absence seizures in rats.