Despite the introduction of more than 15 third generation antiepileptic drugs to the market
from 1990 to the moment, about one third of the epileptic patients still suffer from refractory to
intractable epilepsy. Several hypotheses seek to explain the failure of drug treatments to control epilepsy
symptoms in such patients. The most studied one proposes that drug resistance might be related with
regional overactivity of efflux transporters from the ATP-Binding Cassette (ABC) superfamily at the
blood-brain barrier and/or the epileptic foci in the brain. Different strategies have been conceived to
address the transporter hypothesis, among them inhibiting or down-regulating the efflux transporters or
bypassing them through a diversity of artifices. Here, we review scientific evidence supporting the
transporter hypothesis along with its limitations, as well as computer-assisted early recognition of ABC
transporter substrates as an interesting strategy to develop novel antiepileptic drugs capable of treating
refractory epilepsy linked to ABC transporters overactivity.
Keywords: ABC transporters, ABCB1, ABCG2, antiepileptic drugs, breast Cancer resistance Protein, drug discovery,
P-glycoprotein, refractory epilepsy, transporter hypothesis.
Rights & PermissionsPrintExport