Abstracts

Rationale: Epilepsy is resistant to drug treatment in about one-third of cases, probably due to multidrug resistance induced by conventional antiepileptic drugs (AEDs). The phenomenon is sometimes associated with an overexpression of multidrug resistance gene 1 (MDR1), which is located on chromosome seven and encodes P-glycoprotein (Pgp), a transmembrane protein of 170 kDa. The purpose of this study was to determine if the overexpression of Pgp could be induced in primary rat astrocytes and Madin-Darby canine kidney (MDCK) cells by some of the more commonly used anticonvulsantsMethods: Astrocytes and MDCK cells were treated with topiramate (10 and 100 M), phenobarbital (30 and 300 μM), carbamazepine (30 and 100 μM), phenytoin (30 and 100 μM), levetiracetam (30 and 300 μM) and tiagabine (10 and 30 μM) for 72 h. Western blot analysis was performed to compare the Pgp immunoreactive protein levels in control and drug-treated astrocytes and Results: Topiramate, phenobarbital, carbamazepine and phenytoin induced dose-dependent overexpression of Pgp in rat astrocytes and MDCK cells. The significantly higher levels of Pgp were detected at 30 and 100 μM of carbamazepine and phenytoin and at 30 and 300 μM of phenobarbital with respect to untreated controls. High expression of Pgp was present in topiramate treated cells, even if these values were lower compared to those of the carbamazepine and/or phenytoin treated samples. Tiagabine and levetiracetam produced Pgp expression similar to the control.Conclusions: Treatment with antiepileptic drugs may contribute to the expression in rat astrocytes and MDCK of MDR1 and its protein product, Pgp.