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

Publisher: Bentham Science Publishers

E-ISSN: 1875-5607|17|3|205-215

ISSN: 1389-5575

Source: Mini Reviews in Medicinal Chemistry, Vol.17, Iss.3, 2017-01, pp. : 205-215

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Abstract

Despite the introduction of more than 15 third generation antiepileptic drugs to the marketfrom 1990 to the moment, about one third of the epileptic patients still suffer from refractory tointractable epilepsy. Several hypotheses seek to explain the failure of drug treatments to control epilepsysymptoms in such patients. The most studied one proposes that drug resistance might be related withregional overactivity of efflux transporters from the ATP-Binding Cassette (ABC) superfamily at theblood-brain barrier and/or the epileptic foci in the brain. Different strategies have been conceived toaddress the transporter hypothesis, among them inhibiting or down-regulating the efflux transporters orbypassing them through a diversity of artifices. Here, we review scientific evidence supporting thetransporter hypothesis along with its limitations, as well as computer-assisted early recognition of ABCtransporter substrates as an interesting strategy to develop novel antiepileptic drugs capable of treatingrefractory epilepsy linked to ABC transporters overactivity.