Potential role of multidrug resistant proteins in refractory epilepsy and antiepileptic drugs interactions
-
Alberto Lazarowski
and
Liliana Czornyj
Abstract
Epilepsy is a common neurological disorder. About one-third of epilepsy patients have a multidrug resistance (MDR) phenotype and develop refractory epilepsy (RE). Changes in the properties of the antiepileptic drugs (AEDs) targets resulting in reduced drug sensitivity, can’t explain the MDR phenotype. This particular refractoriness is now attributed to overexpression of multidrug transporters in brain, leading to impaired access of AEDs to CNS targets, and it was documented in both human as well as in experimental models of RE. Single nucleotide polymorphism (SNP) identified in the MDR1-ABCB1gene (C3435T/CC-genotype) is associated with increased intestinal expression of P-glycoprotein (P-gp) that affects levels of AEDs in plasma. The functional studies of P-gp using P-gp inhibitors could show the still unclear clinical impact of ABCB1 polymorphisms on AEDs resistance. Some drug-drug interactions previously believed to be cytochrome P450 (CYP) mediated are now also considered to be due to the modulation of multidrug-transporters. Because in certain cases pharmacoresistance can be overcome by add-on therapy, co-administered P-gp inhibitors could contribute to the effectiveness of AEDs treatment in RE. And in this regard, perhaps we can postulate to P-gp as a new clinical therapeutic target in multidrug-refractory epilepsy.
©2011 by Walter de Gruyter Berlin New York
Articles in the same Issue
- Editorial
- Pharmacogenomics and drug interactions. A specific journal
- Publisher's Note
- Publisher's Note
- Reviews
- Pharmacogenetics of the antiepileptic drugs phenytoin and lamotrigine
- Effect of apolipoprotein E polymorphism on statin-induced decreases in plasma lipids and cardiovascular events
- Minireview
- Potential role of multidrug resistant proteins in refractory epilepsy and antiepileptic drugs interactions
- Original Article
- Biological and genetic factors associated with ABCB1 and pregnane-X-receptor expressions in peripheral blood mononuclear cells in the STANISLAS cohort
- Short Communications
- ABCA1 and ABCG1 expressions are regulated by statins and ezetimibe in Caco-2 cells
- Tumor necrosis factor-α and interleukin-6 expression in leukocytes and their association with polymorphisms and bone markers in diabetic individuals treated with pioglitazone
- Short Report
- From systems biology and functional genomics to personalized health
Articles in the same Issue
- Editorial
- Pharmacogenomics and drug interactions. A specific journal
- Publisher's Note
- Publisher's Note
- Reviews
- Pharmacogenetics of the antiepileptic drugs phenytoin and lamotrigine
- Effect of apolipoprotein E polymorphism on statin-induced decreases in plasma lipids and cardiovascular events
- Minireview
- Potential role of multidrug resistant proteins in refractory epilepsy and antiepileptic drugs interactions
- Original Article
- Biological and genetic factors associated with ABCB1 and pregnane-X-receptor expressions in peripheral blood mononuclear cells in the STANISLAS cohort
- Short Communications
- ABCA1 and ABCG1 expressions are regulated by statins and ezetimibe in Caco-2 cells
- Tumor necrosis factor-α and interleukin-6 expression in leukocytes and their association with polymorphisms and bone markers in diabetic individuals treated with pioglitazone
- Short Report
- From systems biology and functional genomics to personalized health
