A Novel Approach to Refractory Epilepsy by Targeting Pgp Peripherally and Centrally: Therapeutic Targets and Future Perspectives

Abstract

Abstract:: Refractory epilepsy is a type of epilepsy involving seizures uncontrolled by first or second-line anticonvulsant drugs at a regular therapeutic dose. Despite considerable growth in epileptic pharmacotherapy, one-third of the patients are resistant to current therapies. In this, the mechanisms responsible for resistant epilepsy are either increased expulsion of an-tiepileptic drugs (AEDs) by multidrug resistance (MDR) transporters from the epileptogenic tissue or reduced sensitivity of drug in epileptogenic brain tissue. The difficulty to treat refractory epilepsy is because of drug resistance due to cellular drug efflux, use of drug monotherapy, and subtherapeutic dose administration. Increased expression of Pgp is also responsible for resistance epilepsy or refractory epilepsy. Increase glutamate expression via inhibition of cyclooxygenase-II (COX-II) en-zyme also upregulate P-glycoprotein (Pgp) expression and augment instance of recurrent seizures. Peripheral and central in-hibition of Pgp is a powerful tool to control this drug resistance epilepsy. Drug resistance primarily involves multidrug re-sistance (MDR1) gene which is responsible for encoding P-glycoprotein (PgP1 or MDR1). Currently, there is no drug under clinical practice which inhibits MDR1. The present review cites some drugs like calcium channel blockers, COX-II inhibi-tors, and glutamate receptors antagonists that inhibit P-gp. The exploitation of these targets may emerge as a beneficial ap-proach for patients with drug-resistant epilepsy. The present review further highlights the mechanistic role of Pgp in drug-resistant epilepsy, glutamate role in drug efflux, and management approach.

Determination of oxidative stress level and some antioxidant activities in refractory epilepsy patients

“…The age range of the control group was 34 ± 13. Most of the subjects included in this study were patients whose seizures could not be fully controlled despite using effective doses of 1st generation and 2nd generation antiepileptic drugs 31 . All of the patients were examined in detail and EEG and IMR of the patients were taken.…”