ABSTRACT:BACKGROUND: Presently, treatment of epilepsy with standard anti-epileptic drugs is associated with a number of shortcomings inviting us to study newer agents that would overcome these problems or search for the drugs or substances, which would enhance the efficacy or reduce the dose or toxicity of these standard anti-epileptic drugs. Ganaxolone (GNX) (3α-hydroxy-3β-methyl-5α-pregnan-20-one), a synthetic analog of the endogenous neurosteroid allopregnanolone and a positive allosteric modulator of GABAA receptors, may represent a new treatment approach for epilepsy. AIM: To evaluate the effect of Ganaxolone on maximal electroshock (MES) induced and Pentylenetetrazol (PTZ) induced convulsions and also their effect in combination with conventional antiepileptic drugs (CAEDs). MATERIAL AND METHODS:Wister strain albino rats weighing 200-250 gm were used. Effects of Ganaxolone (5 &10 mg/kg) alone and in combination with standard drugs were studied in MES and PTZ induced seizure models. Abolition of tonic hind limb extension was an index of anticonvulsant activity in MES, while for PTZ seizures; failure to observe clonus for 5sec duration for 30min was the index. Following that, percentage inhibition was calculated. STATISTICS: ANOVA followed by Newman-Keuls Multiple Comparison Test was used for analysis of data between the groups. RESULTS: In MES seizures, significant antiepileptic activity was observed with 10mg of Ganaxolone compared to control group but has less activity when compared to that of Phenobarbitone. In PTZ induced convulsions, the anti-epileptic effect of Sodium Valproate was higher than Ganaxolone, but both were statistically significant as compared to control. In PTZ-induced seizures, augmented effects were obtained when Ganaxolone was combined with sodium valproate i.e. 55%. CONCLUSIONS:The results provide a lead for potential benefit of adding Ganaxolone to Sodium Valproate in the treatment of epilepsy, which needs to be explored further.