Signalingto P-glycoprotein - A new therapeutic target to treat drug-resistant epilepsy?

Anika M.S. Hartz, Sylvia Notenboom, Björn Bauer

Research output: Contribution to journalReview articlepeer-review

26 Scopus citations


Epilepsy affects more than 60 million people worldwide. While most patients can be treated with antiepileptic drugs, up to 40% of patients respond poorly to pharmacotherapy. This drug resistance is not well understood and presents a major clinical problem. In this short review we provide background information on one potential cause of antiepileptic drug resistance, namely, upregulation of the drug efflux transporter P-glycoprotein at the blood-brain barrier. We summarize recent findings that connect antiepileptic drug resistance with P-glycoprotein upregulation and show a mechanistic link between seizures and upregulation of this transporter. We provide an overview of results demonstrating that glutamate released during seizures signals through N-methyl-D-aspartate (NMDA) receptor and cyclooxygenase-2 (COX-2) to increase P-glycoprotein. In this context we discuss the NMDA receptor and COX-2 as potential therapeutic targets and provide information on current clinical trials on drug-resistant epilepsy involving blood-brain barrier efflux transporters. Finally, we provide a perspective on future research that could help improve the treatment of drug-resistant epilepsy.

Original languageEnglish
Pages (from-to)393-397
Number of pages5
JournalDrug News and Perspectives
Issue number7
StatePublished - Sep 2009

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery


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