Skip Navigation


Brain Advance Access originally published online on November 29, 2005
Brain 2006 129(1):18-35; doi:10.1093/brain/awh682
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
129/1/18    most recent
awh682v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (47)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Remy, S.
Right arrow Articles by Beck, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Remy, S.
Right arrow Articles by Beck, H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 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

Review Article

Molecular and cellular mechanisms of pharmacoresistance in epilepsy

Stefan Remy and Heinz Beck

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

Correspondence to: Heinz Beck, MD, Department of Epileptology, University of Bonn Medical Center, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany E-mail: heinz.beck{at}ukb.uni-bonn.de

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.

Key Words: epilepsy; pharmacoresistance; anti-epileptic drugs; multidrug transporter; ion channel

Abbreviations: AED = anti-epileptic drug; ABC = adenosine triphosphate-binding cassette; PGP = P-glycoprotein

Received April 13, 2005. Revised July 22, 2005. Accepted October 13, 2005.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Arch NeurolHome page
M. A. Dichter
Emerging Concepts in the Pathogenesis of Epilepsy and Epileptogenesis
Arch Neurol, April 1, 2009; 66(4): 443 - 447.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
P. J. Jones, E. C. Merrick, T. W. Batts, N. J. Hargus, Y. Wang, J. P. Stables, E. H. Bertram, M. L. Brown, and M. K. Patel
Modulation of Sodium Channel Inactivation Gating by a Novel Lactam: Implications for Seizure Suppression in Chronic Limbic Epilepsy
J. Pharmacol. Exp. Ther., January 1, 2009; 328(1): 201 - 212.
[Abstract] [Full Text] [PDF]

Home page
 NeuroscientistHome page
J. Epsztein, Y. Ben-Ari, A. Represa, and V. Crepel
Late-Onset Epileptogenesis and Seizure Genesis: Lessons From Models of Cerebral Ischemia
Neuroscientist, February 1, 2008; 14(1): 78 - 90.
[Abstract] [PDF]

Home page
 Stem CellsHome page
A. K. Shetty and B. Hattiangady
Concise Review: Prospects of Stem Cell Therapy for Temporal Lobe Epilepsy
Stem Cells, October 1, 2007; 25(10): 2396 - 2407.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurophysiol.Home page
M. Weiergraber, M. Henry, K. Radhakrishnan, J. Hescheler, and T. Schneider
Hippocampal Seizure Resistance and Reduced Neuronal Excitotoxicity in Mice Lacking the Cav2.3 E/R-Type Voltage-Gated Calcium Channel
J Neurophysiol, May 1, 2007; 97(5): 3660 - 3669.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
K. Jandova, D. Pasler, L. L. Antonio, C. Raue, S. Ji, M. Njunting, O. Kann, R. Kovacs, H.-J. Meencke, E. A. Cavalheiro, et al.
Carbamazepine-resistance in the epileptic dentate gyrus of human hippocampal slices
Brain, December 1, 2006; 129(12): 3290 - 3306.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.