Modulating P-glycoprotein regulation: Future perspectives for pharmacoresistant epilepsies?

摘要: Summary Enhanced brain efflux of antiepileptic drugs by the blood–brain barrier transporter P-glycoprotein is discussed as one mechanism contributing to pharmacoresistance epilepsies. overexpression has been proven occur a consequence seizure activity. Therefore, blocking respective signaling events should help improve penetration and efficacy substrates. A series recent studies revealed key factors involved in seizure-associated transcriptional activation P-glycoprotein. These data suggested several interesting targets, including N-methyl-d-aspartate (NMDA) receptor, inflammatory enzyme cyclooxygenase-2, prostaglandin E2 EP1 receptor. targets have further evaluated rodent models, demonstrating that targeting these can control expression, drug penetration, overcome pharmacoresistance. In general, approach offers particular advantages over inhibition it preserves basal function. this review different strategies for upregulation, their therapeutic promise drawbacks are discussed. Moreover, pros cons compared those alternative transporter-associated resistance. Regarding future perspectives novel approach, there an obvious need more clearly define clinical relevance overexpression. context current efforts discussed, development imaging tools allow evaluation function individual patients.