A novel approach of targeting refractory epilepsy: Need of an hour

Abstract

The refractory epilepsy adds to the global burden of epilepsy as about 25 % of all patients with epilepsy present drug-resistant epilepsy. The P-glycoprotein (P-gp) plays a vital role in the mechanism of resistance in epilepsy. The AED levels in the brain are regulated by the P-gp transport. The upregulation of P-gp results in low concentration of AEDs inside the brain parenchyma and thus leads to resistance. There are three main conditions which lead to decrease transport of AEDs in refractory epilepsy. First being AEDs as substrate of P-gp; secondly, the elevated expression of P-gp in patients with drug resistant epilepsy as compared to drug-responsive patients; thirdly, the low brain AED concentration in refractory epilepsy in comparison to drug-responsive epilepsy. Therefore, determination of P-gp substrate should be a criterion for the selection of new AED for management of refractory epilepsy. This review highlights various tools which help in identification of P-gp substrates and also illustrates a concept of using various novel non-P-gp substrates which can cross the blood brain barrier and leads to enhanced accumulation inside the brain. Hence, these non P-gp substrates can be used as an add on treatment for the management of resistant epilepsy.

Keywords: Antiepileptic drugs; Non-P-gp substrates; P-glycoprotein; Resistant epilepsy.