IngentaConnect Basic Science

Authors: Wang-Tilz, Ying; Tilz, Christian; Wang, Bing; Tilz, Gernot P.; Stefan, Hermann; Bercovici, Eduard; Cortez, Miguel A.; Wang, Xiaomei; Snead, O. Carter; Debanne, Dominique; Thompson, Scott M.; Gähwiler, Beat H.; Patrylo, Peter R.; Browning, Ronald A.; Cranick, Scott; Musto, Alberto; Bazan, Nicolas G.; Tsai, Min-Lan; Leung, L. Stan; Gorji, Ali; Stemmer, Nina; Rambeck, Bernhard; Jürgens, Uwe; May, Theodor; Pannek, Heinz Wolfgang; Behne, Friedrich; Ebner, Alois; Straub, Hiedrun; Speckmann, Erwin-Josef

Abstract:

Influence of Lamotrigine and Topiramate on MDR1 Expression in Difficult-to-Treat Temporal Lobe Epilepsy

<namegroup type="author"> <name type="author"> <forenames>Ying</forenames> <surname>Wang-Tilz</surname> </name>, <name type="author"> <forenames>Christian</forenames> <surname>Tilz</surname> </name>, <name type="author"> <forenames>Bing</forenames> <surname>Wang</surname> </name>, <name type="author"> <forenames>Gernot P.</forenames> <surname>Tilz</surname> </name>, and <name type="author"> <forenames>Hermann</forenames> <surname>Stefan</surname> </name> </namegroup> Some individuals with epilepsy appear resistant to most or all antiepileptic medications. One possible explanation for this resistance is the presence of a gene called MDR1 that causes production in the brain of a substance called p-glycoprotein (P-gp). We studied a model of epilepsy in rats produced by repeated injections of Coriaria lactone, an epileptogenic plant toxin. The clinical antiepileptic drugs, topiramate and lamotrigine, significantly reduced seizures. With these two drugs, P-gp was not increased in brain. In contrast, carbamazepine and valproate did increase brain P-gp, and these drugs were less beneficial against the seizures. These results suggest that attention could usefully be paid to whether medications activate multiple drug-resistance genes in brain, because such an effect could counteract the effectiveness of a medication. Epilepsia 2006;47(2).