The Antiepileptic Effect of Riluzole and In Combination with Phenytoin On Maximal Electroshock Induced Seizures In Albino Rats: An Experimental Study

Abstract

Despite the introduction of several new therapeutic options, a significant fraction of the patients with epilepsy continue to live with uncontrolled seizures. Although large no. of antiepileptic drug area available in the market, most of these agents have a limited spectrum of antiepileptic activity and all have certain negative properties that limit their utility and complicate patient management, so there is still a need for an ideal antiepileptic agent with properties like broad spectrum activity, rapid onset of action, least side effects, good oral bioavailability and low cost. Methodology: Albino rats weighing 150-200g, 6-8 weeks old of either sex, were used in the study. Rats were randomly allocated in to 9 groups each group consists of six. Group 1: control II, III: Riluzole 5, 10mg/kg respectively, IV, V, VI: Phenytoin 25, 50, 100mg/kg respectively. VII, VIII, IX: Riluzole 10mg/kg in combination with Phenytoin 25, 50, 100mg/kg respectively. Drugs were administered to all groups orally by orogastric tube, as per the study subgroups. 30miutes later the rats were subjected to an electric shock by using an electro convulsiometer: Presence or absence of hind limb extensor, duration of Hind limb tonic extensor (HLTE) phase & duration of clonus in sec. Result: Riluzole at both dosages of 5 & 10mg/kg did not modify the MES induced convulsions. Phenytoin at a dose of 25mg/kg & 50mg/kg could not abolish the hind limb extension. However phenytoin at 100mg/kg produced 100% abolition of Hind Limb Extension. Phenytoin at 25mg/kg & 50mg/kg dosage insignificantly reduced the duration of Hind Limb Extensions without any effect on clonic phase. At the same time phenytoin at 100mg/kg significantly increased the duration of clonus from 9, 8 to 18, 3 seconds, but interestingly when Riluzole 10mg/kg was combined with
Phenytoin 50mg/kg, the Hind Limb Extension was abolished in 50% animals. When the dose of Phenytoin was further increased to 100mg it produced 100% protection by abolishing Hind Limb Extension. Similar effects were produced when Riluzole was combined with 100mg of Phenytoin. Conclusion: Riluzole alone was found to be ineffective against MES induced seizures, however it was found to enhance the antiepileptic effect of phenytoin against MES induced seizures.