Computer-Aided Recognition of ABC Transporters Substrates and Its Application to the Development of New Drugs for Refractory Epilepsy

MANUEL COUYOUPETROU; MELISA GANTNER; MAURICIO DI IANNI; PABLO PALESTRO; ANDREA ENRIQUE; LUCIANA GAVERNET; MARÍA ESPERANZA RUIZ; GUIDO PESCE; LUIS BRUNO-BLANCH; ALAN TALEVI

MINI-REVIEWS IN MEDICINAL CHEMISTRY

BENTHAM SCIENCE PUBL LTD

Lugar: Oak Park; Año: 2016 vol. 17 p. 205 - 215

1389-5575

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 of 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 transporters substrates as an interesting strategy to develop novel antiepileptic drugs capable of treating refractory epilepsy linked to ABC transporters overactivity.