PT  - JOURNAL ARTICLE
AU  - Robert W. Robey
AU  - Alberto Lazarowski
AU  - Susan E. Bates
TI  - P-Glycoprotein—a Clinical Target in Drug-Refractory Epilepsy?
AID  - 10.1124/mol.108.046680
DP  - 2008 May 01
TA  - Molecular Pharmacology
PG  - 1343--1346
VI  - 73
IP  - 5
4099  - http://molpharm.aspetjournals.org/content/73/5/1343.short
4100  - http://molpharm.aspetjournals.org/content/73/5/1343.full
SO  - Mol Pharmacol2008 May 01; 73
AB  - 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.