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CNS transporters and drug delivery in epilepsy

Heidrun Potschka, Hiram Luna-Munguia1

  • 1Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig-Maximilians-University, Koeniginstr. 16, D-80539 Munich, Germany. potschka@pharmtox.vetmed.uni-muenchen.de.

Current Pharmaceutical Design
|June 25, 2013
PubMed

Insights

Drug resistance in epilepsy is complex. Enhanced drug efflux via P-glycoprotein may contribute to antiepileptic drug failure, suggesting potential therapeutic targets.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Epileptology

Background:

  • Antiepileptic drug (AED) therapy is ineffective for a significant portion of epilepsy patients.
  • Epilepsy drug resistance is a complex, multi-factorial issue.
  • Enhanced efflux transport of AEDs is a proposed mechanism contributing to therapeutic failure.

Purpose of the Study:

  • To explore the role of P-glycoprotein (P-gp) in antiepileptic drug resistance.
  • To review evidence linking P-gp expression to AED response.
  • To discuss the potential of P-gp modulators as a therapeutic strategy.

Main Methods:

  • Review of epidemiological data, human epileptic tissue findings, and rodent models.
  • Analysis of studies investigating P-glycoprotein expression and AED response.
  • Consideration of findings from add-on therapy with P-gp modulators in epilepsy models.

Main Results:

  • Increased P-glycoprotein expression is associated with reduced AED efficacy in preclinical models and potentially in patients.
  • P-glycoprotein modulators have shown efficacy in a rat model of drug-resistant epilepsy.
  • The precise functional relevance of blood-brain barrier efflux in human epilepsy requires further investigation.

Conclusions:

  • P-glycoprotein-mediated efflux is a significant factor in antiepileptic drug resistance.
  • Targeting P-glycoprotein may offer a novel therapeutic approach for drug-resistant epilepsy.
  • Further research, including advanced imaging techniques, is needed to fully elucidate the role of efflux transporters in human epilepsy.

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