Discovering New Antiepileptic Drugs Addressing the Transporter Hypothesis of Refractory Epilepsy: Structure-Based Approximations

Abstract

About one third of the epileptic patients cannot control their symptoms with antiepileptic drugs, despite the introduction of more than 15 novel therapeutic agents to the market since 1990. The most studied hypothesis to explain the phenomenon of drug resistance in epilepsy maintains that it might be related to regional overactivity of efflux transporters from the ATP­binding cassette (ABC) superfamily at the blood–brain barrier and/or the epileptic foci. Here, we review scientific evidence supporting the transporter hypothesis along with its limitations. We also cover some technical aspects of computational and experimental approaches used for the early detection of substrates of such efflux systems.