Epilepsy Research Today is a free monthly online journal that collates and summarizes the latest research about Epilepsy, including details on symptoms, causes, treatment, drugs, information.

P-glycoprotein--a clinical target in drug-refractory epilepsy?

Robey RW, Lazarowski A, Bates SE

Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. robeyr@mail.nih.gov

ATP-binding cassette transporters such as P-glycoprotein (Pgp), multidrug resistance-associated protein, and breast cancer resistance protein are known to transport a wide range of substrates and are highly expressed in the capillary endothelial cells that form part of the blood-brain barrier. It is noteworthy that P-glycoprotein has been shown to be up-regulated in animal models of refractory epilepsy, and adding a Pgp inhibitor to treatment regimens has been shown to reverse the drug-resistant phenotype. Limited data have suggested a role for Pgp in epilepsy in humans as well. However, few epilepsy drugs have been shown to be transported by Pgp, leading to controversy over whether Pgp actually plays a role in drug-resistant epilepsy. In this issue of Molecular Pharmacology, Bauer et al. (p. 1444) demonstrate that glutamate can cause localized up-regulation of Pgp via cyclooxygenase-2 (COX-2) and that this phenomenon can be prevented with COX-2 inhibitors. Localized rather than global up-regulation of Pgp may explain some of the difficulty investigators have had in proving a role for Pgp in epilepsy. The results add new support for future clinical trials targeting Pgp expression in drug-refractory epilepsy.

Published 17 April 2008 in Mol Pharmacol, 73(5): 1343-6.
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