期刊
DRUG NEWS & PERSPECTIVES
卷 22, 期 7, 页码 393-397出版社
PROUS SCIENCE, SAU-THOMSON REUTERS
DOI: 10.1358/dnp.2009.22.7.1401354
关键词
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资金
- University of Minnesota CIA [20919]
- AACP NIP
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 upregutation and show a mechanistic link between seizures and upregutation 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.
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