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Brain Advance Access published online on November 29, 2005
Brain, doi:10.1093/brain/awh682
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© The Author (2005). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received April 13, 2005
Revised July 22, 2005
Accepted October 13, 2005

Review Article

Molecular and cellular mechanisms of pharmacoresistance in epilepsy

Stefan Remy 1 and Heinz Beck 1 *

1 Department of Epileptology, University of Bonn Medical Center, Bonn, Germany

* To whom correspondence should be addressed.
Heinz Beck, E-mail: heinz.beck{at}ukb.uni-bonn.de


  Abstract

Epilepsy is a common and devastating neurological disorder. In many patients with epilepsy, seizures are well-controlled with currently available anti-epileptic drugs (AEDs), but a substantial (~30%) proportion of patients continue to have seizures despite carefully optimized drug treatment. Two concepts have been put forward to explain the development of pharmacoresistance. The transporter hypothesis contends that the expression or function of multidrug transporters in the brain is augmented, leading to impaired access of AEDs to CNS targets. The target hypothesis holds that epilepsy-related changes in the properties of the drug targets themselves may result in reduced drug sensitivity. Recent studies have started to dissect the molecular underpinnings of both transporter- and target-mediated mechanisms of pharmacoresistance in human and experimental epilepsy. An emerging understanding of these underlying molecular and cellular mechanisms is likely to provide important impetus for the development of new pharmacological treatment strategies.

Keywords: epilepsy; pharmacoresistance; anti-epileptic drugs; multidrug transporter; ion channel.
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