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

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.

• Authors: Ying Wang-Tilz, Christian Tilz, Bing Wang, Gernot P Tilz, Hermann Stefan
• Journal: Epilepsia (Epilepsia) Vol. 47 Issue 2 Pg. 233-9 (Feb 2006) ISSN: 0013-9580 [Print] United States
• PMID: 16499746 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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