Abolition of Seizure Provoking Effect of Sumatriptan by Fluoxetine in Pentylenetetrazol Induced Seizures in Rats

Objectives: The objective was to evaluate the seizure provoking effect of sumatriptan, and its abolition with fluoxetine in the pentylenetetrazolinduced seizures in rats. Methods: 100 Sprague-Dawley rats of either sex were randomized into 10 groups with each group consisting 10 rats. The first group was taken as a control group which received distilled water. The second group and the third group were evaluated with standard anticonvulsant drug sodium valproate in the dose of 200 mg/kg and 250 mg/kg, respectively. The fourth group received sumatriptan in the dose 6 mg/kg. The fifth and sixth groups were evaluated for effect of fluoxetine in the dose of 6 mg/kg and 10 mg/kg, respectively. The seventh group was evaluated for the combined effect of sumatriptan 6 mg/kg and sodium valproate 200 mg/kg. The eighth group was administered fluoxetine 6 mg/kg and sodium valproate 200 mg/kg. The ninth group was evaluated for a combined effect of fluoxoetine 6 mg/kg and sumatriptan 6 mg/kg. The tenth group was evaluated for the combined effect of three drugs fluoxetine 6 mg/kg, sumatriptan 6 mg/kg, and sodium valproate 200 mg/kg. The rats were screened for the effect of various drugs by inducing seizures with pentylenetetrazol. The rats were analyzed for the parameters, i.e., the time for the onset of seizures, duration of tonic-clonic seizures, and for post seizure mortality up to 24 hrs. Results: Sumatriptan reduced the seizure threshold in rats, and it has abolished the seizure protective effect of sodium valproate. Sodium valproate and fluoxetine had dose dependent seizure protective effect. Fluoxetine abolished the seizure threshold lowering effect of sumatriptan. Fluoxetine and sodium valproate combination produced additive seizure productive effect. The combination of sumatriptan, fluoxetine, and sodium valproate also raised the seizure threshold. Conclusion: The seizure threshold lowering effect of sumatriptan was abolished by co-administration of fluoxetine.