ABSTRACT
Background: Epilepsy is one of the most common diseases of the brain, affecting at least 50 million persons worldwide. Although the causes of epilepsy are many, the fundamental disorder is secondary to abnormal synchronous discharges of a network of neurons. There are currently differently antiepileptic drugs used in the treatment of seizures but with a lot of dose-dependent adverse effect, hence the need to reduce their dose and add an adjunct therapy. In recent years, there has been increasing evidence that serotonergic neurotransmission modulates a wide variety of experimentally induced seizures. Also, it has been shown that several anti-epileptic drugs increase endogenous extracellular 5-HT concentration. 5-HT receptors are expressed in almost all networks involved in epilepsies. This study investigates the anticonvulsant activity of phenobarbitone and sodium valproate when combined with buspirone, sumatriptan (serotonin receptor agonists) and fluoxetine (serotonin reuptake inhibitor).
Method: Three (3) basic methods were employed in this study which includes, pentylenetetrazol (PTZ)- induced convulsion method, maximum electroshock (MES)-induced convulsion method and the strychnine-induced convulsion method. For PTZ-induced convulsion method, 20 mice in all were employed; they were split into five groups of 4 mice each. Mice in group I were treated with 0.2 ml of distilled water as negative control, group II mice were administered 20 mg/kg and 150 mg/kg of fluoxetine and sodium valproate respectively, group III mice were administered 20 mg/kg and 150 mg/kg of sumatriptan and sodium valproate respectively, also group IV mice were administered 5 mg/kg and 150 mg/kg of buspirone and sodium valproate respectively while group V were administered 150mg/kg of sodium valproate as positive standard. One hour later, 70 mg/kg PTZ was administered intraperitoneally (i.p) to all the mice in all group. The time of PTZ administration, onset of CNS activity, and mortality protection were then recorded. The above procedure was repeated using phenobarbitone (15 mg/kg) as positive standard.
For STN-induced convulsion, the above procedures were repeated but strychnine (1 mg/kg) was used in place of PTZ. For MES-induced convulsion, all mice were subjected to electroshock at a current of 50mA for 0.2 seconds through a pair of ear clip electrodes after one hour of administering the drugs as done in the other methods.