title: Computer-Aided Recognition of ABC Transporters Substrates and Its Application to the Development of New Drugs for Refractory Epilepsy.
abstract: 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.
authors.forename: Manuel
authors.initials: M
authors.lastname: Couyoupetrou
authors.forename: Melisa E
authors.initials: ME
authors.lastname: Gantner
authors.forename: Mauricio E
authors.initials: ME
authors.lastname: Di Ianni
authors.forename: Pablo H
authors.initials: PH
authors.lastname: Palestro
authors.forename: Andrea V
authors.initials: AV
authors.lastname: Enrique
authors.forename: Luciana
authors.initials: L
authors.lastname: Gavernet
authors.forename: Maria E
authors.initials: ME
authors.lastname: Ruiz
authors.forename: Guido
authors.initials: G
authors.lastname: Pesce
authors.affiliation: Department of Biological Sciences, Faculty of Exact Sciences, University of La Plata, La Plata,. Argentina.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Bruno-Blanch
authors.forename: Alan
authors.initials: A
authors.lastname: Talevi
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D017076:Computer-Aided Design; D055808:Drug Discovery / Q000379:methods*; D000069279:Drug Resistant Epilepsy / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans
chemical_list: D018528:ATP-Binding Cassette Transporters