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ABC Transporters and Drug Resistance in Patients with Epilepsy

Feldmann, M; Koepp, M; (2016) ABC Transporters and Drug Resistance in Patients with Epilepsy. Current Pharmaceutical Design , 22 (38) pp. 5793-5807. 10.2174/1381612822666160810150416. Green open access

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Abstract

Resistance to antiepileptic drugs (AED) remains a major problem in clinical epileptology. This pharmacoresistance is independent of the choice of AEDs. Different hypotheses have been proposed to explain the neurobiological basis for pharmacoresistance in epilepsy. The transporter hypothesis is the mostly investigated theory. Hereby, overexpression of multidrug efflux transporters, such as P-glycoprotein (Pgp), at the blood-brain-barrier (BBB) is thought to be involved in pharmacoresistance in epilepsy by extruding AEDs from their target site. Accumulating evidence supports an overexpression of Pgp in pharmacoresistant epilepsy. Molecular Imaging studies provide unique opportunities for the in-vivo study of the transporter hypothesis in the central nervous system (CNS). Several studies demonstrated that positron emission tomography (PET) with [11C]-radiolabled Pgp substrates is a promising tool for in vivo investigation of Pgp function at the rat, monkey and human BBB. Quantification of Pgp over activity in epilepsy patients by in vivo imaging could be highly useful because altered treatment strategies or novel AED could then be applied.

Type: Article
Title: ABC Transporters and Drug Resistance in Patients with Epilepsy
Open access status: An open access version is available from UCL Discovery
DOI: 10.2174/1381612822666160810150416
Publisher version: https://doi.org/10.2174/1381612822666160810150416
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Pharmacology & Pharmacy, Blood-brain-barrier, P-glycoprotein, positron emission tomography, drug transporter, epilepsy, BLOOD-BRAIN-BARRIER, TEMPORAL-LOBE EPILEPSY, P-GLYCOPROTEIN FUNCTION, POSITRON-EMISSION-TOMOGRAPHY, MEDICALLY INTRACTABLE EPILEPSY, FOCAL CORTICAL DYSPLASIA, CENTRAL-NERVOUS-SYSTEM, CURRENT ANIMAL-MODELS, BREAST-CANCER CELLS, MULTIDRUG-RESISTANCE
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
URI: https://discovery.ucl.ac.uk/id/eprint/10075967
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