Interaction profile of Zizyphus jujuba with phenytoin, phenobarbitone, and carbamazepine in maximal electroshock-induced seizures in rats

Abstract

The antiepileptic effect of hydroalcoholic extract of Zizyphus jujuba (HEZJ) in experimental seizures was demonstrated earlier. The present study aimed to evaluate the pharmacokinetic and pharmacodynamic interactions of HEZJ with phenytoin (PHT), phenobarbitone (PB), and carbamazepine (CBZ) in maximal electroshock (MES)-induced seizures in male Wistar rats. Maximal electroshock (70 mA, 9 ms pulse width, 0.2 s) was used to induce seizures. Blood samples were collected at two time points for estimation of serum PHT, PB, and CBZ levels using high-pressure liquid chromatography (HPLC). Co-administration of HEZJ with the sub-therapeutic doses of PHT, PB, and CBZ exhibited 66.7, 66.7, and 50.0% protection against tonic hind limb extension as compared to 33.3, 33.3, and 50% protection respectively, in the groups treated with PHT, PB, and CBZ alone in their sub-therapeutic doses. Co-administration of HEZJ with the sub-therapeutic doses of these antiepileptic drugs (AEDs) showed significant improvement in cognitive functions as compared to MES group as well as these AEDs alone. A significant increase in glutathione levels and decrease in malondialdehyde levels were observed with pretreatment of HEZJ with the sub-therapeutic doses of these AEDs. Co-administration of HEZJ with PHT, PB, and CBZ did not cause any significant changes in the serum concentrations of these AEDs. The results of the present study indicate that the co-administration of HEZJ with sub-therapeutic doses of PHT and PB potentiated the antiepileptic effect of PHT and PB in MES-induced seizures with no change found in the antiepileptic effect of CBZ.