Influence of lamotrigine and topiramate on MDR1 expression in difficult-to-treat temporal lobe epilepsy

Epilepsia. 2006 Feb;47(2):233-9. doi: 10.1111/j.1528-1167.2006.00414.x.

Abstract

Purpose: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Animals
  • Anticonvulsants / pharmacology*
  • Anticonvulsants / therapeutic use
  • Brain / drug effects
  • Brain / metabolism*
  • Carbamazepine / pharmacology
  • Disease Models, Animal
  • Drug Resistance
  • Epilepsy, Temporal Lobe / chemically induced
  • Epilepsy, Temporal Lobe / genetics*
  • Epilepsy, Temporal Lobe / prevention & control*
  • Fructose / analogs & derivatives*
  • Fructose / pharmacology
  • Gene Expression / drug effects
  • Genes, MDR / drug effects*
  • Genes, MDR / genetics*
  • Humans
  • Immunohistochemistry
  • Kindling, Neurologic / drug effects
  • Lactones
  • Lamotrigine
  • Male
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Topiramate
  • Triazines / pharmacology*
  • Valproic Acid / pharmacology

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anticonvulsants
  • Lactones
  • Triazines
  • Topiramate
  • Fructose
  • Carbamazepine
  • Valproic Acid
  • coriaria lactone
  • Lamotrigine