Influence of lamotrigine and topiramate on MDR1 expression in difficult-to-treat temporal lobe epilepsy.
OBJECTIVE
Overexpression of the multiple drug resistance gene 1 (MDR1) was quantified in brain tissue from Coriaria lactone (CL)-kindled Sprague-Dawley (SD) rats after treatment with lamotrigine (LTG) or topiramate (TPM) and compared with that found in rats treated with carbamazepine (CBZ) and valproate (VPA).


METHODS
Twenty-five CL-kindled SD rats were randomized into five groups (n = 5 for each group) to receive once-daily feeding of CBZ, VPA, TPM, and LTG as the monotherapy equivalent of maximum human adult dosage, or normal saline (NS control) for 1 month. The expression of P-gp in brain tissues of all rats was quantified by using an image analysis and measuring system (Image Pro-plus 4.0). Mean area and mean integrated optical density (mean IOD) of P-gp expression were calculated. In addition, the changes in seizure severity were analyzed via video-camera monitoring.


RESULTS
A significant decrease in the number and duration of seizures with antiepileptic drug (AED) treatment was observed in the TPM and LTG groups. The mean area and mean IOD of P-gp expression were highest in the CBZ group and next highest in the VPA group; much lower values were measured in the TPM and LTG groups, and the lowest in the NS control group (p < 0.05).


CONCLUSIONS
TPM and LTG significantly inhibited seizures in this CL model. The expression of P-gp was not significantly increased by TPM or LTG treatment in this study.
Wang-Tilz
Ying
Y
Department of Neurology, Epilepsy Center Erlangen, University of Erlangen-Nuremberg, 91054 Erlangen, Germany.
Tilz
Christian
C
Wang
Bing
B
Tilz
Gernot P
GP
Stefan
Hermann
H
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002220:Carbamazepine / Q000494:pharmacology; D004195:Disease Models, Animal; D004351:Drug Resistance; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000235:genetics* / Q000517:prevention & control*; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D019450:Genes, MDR / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007696:Kindling, Neurologic / Q000187:drug effects; D007783:Lactones; D000077213:Lamotrigine; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077236:Topiramate; D014227:Triazines / Q000494:pharmacology*; D014635:Valproic Acid / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000927:Anticonvulsants; D007783:Lactones; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D002220:Carbamazepine; D014635:Valproic Acid; C049836:coriaria lactone; D000077213:Lamotrigine