P-glycoprotein alters blood-brain barrier penetration of antiepileptic drugs in rats with medically intractable epilepsy

Drug Design, Development and Therapy
Aimei MaWeien Yuan

Abstract

P-glycoprotein is one of the earliest known multidrug transporters and plays an important role in resistance to chemotherapeutic drugs. In this study, we detected levels of P-glycoprotein and its mRNA expression in a rat brain model of medically intractable epilepsy established by amygdala kindling and drug selection. We investigated whether inhibition of P-glycoprotein affects the concentration of antiepileptic drugs in cortical extracellular fluid. We found that levels of P-glycoprotein and its mRNA expression were upregulated in epileptic cerebral tissue compared with cerebral tissue from normal rats. The concentrations of two antiepileptic drugs, carbamazepine and phenytoin, were very low in the cortical extracellular fluid of rats with medically intractable epilepsy, and were restored after blockade of P-glycoprotein by verapamil. These results show that increased P-glycoprotein levels alter the ability of carbamazepine and phenytoin to penetrate the blood-brain barrier and reduce the concentrations of these agents in extracellular cortical fluid. High P-glycoprotein levels may be involved in resistance to antiepileptic drugs in medically intractable epilepsy.

References

Sep 1, 1988·The Japanese Journal of Psychiatry and Neurology·K Morimoto, G V Goddard
Mar 1, 1972·Electroencephalography and Clinical Neurophysiology·R J Racine
Apr 25, 2001·British Journal of Clinical Pharmacology·A OwenB K Park
Jan 18, 2002·Journal of Neurochemistry·Robert A Felix, Margery A Barrand
Mar 22, 2002·The Journal of Pharmacology and Experimental Therapeutics·Wolfgang Löscher, Heidrun Potschka
Jul 31, 2003·Epilepsia·Giuseppe CapovillaGiangennero Coppola
Jan 20, 2004·Brain & Development·Giangennaro CoppolaAntonio Pascotto
Aug 26, 2004·The Annals of Pharmacotherapy·Monica A SummersJames W McAuley
Jan 26, 2005·Biochemical Society Transactions·O Polgar, S E Bates
Feb 18, 2005·NeuroRx : the Journal of the American Society for Experimental NeuroTherapeutics·Wolfgang Löscher, Heidrun Potschka
Jul 14, 2005·Progress in Neurobiology·Wolfgang Löscher, Heidrun Potschka
May 13, 2010·Reviews in the Neurosciences·Shanshan Shen, Wandong Zhang
Jan 12, 2011·Epilepsia·Melanie JambroszykHeidrun Potschka
Nov 22, 2011·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·S Pirker, C Baumgartner

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Methods Mentioned

BETA
PCR
electrophoresis
gene knockout

Software Mentioned

SigmaStat

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