The complexity of roles of P-glycoprotein in refractory epilepsy: Pharmacoresistance, epileptogenesis, SUDEP and relapsing marker after surgical treatmentReport as inadecuate




The complexity of roles of P-glycoprotein in refractory epilepsy: Pharmacoresistance, epileptogenesis, SUDEP and relapsing marker after surgical treatment - Download this document for free, or read online. Document in PDF available to download.

ADMET and DMPK, Vol.3 No.2 July 2015. -

As described initially from clinical and experimental studies, P-glycoprotein P-gp plays a central role in the pharmacoresistance of epilepsy, acting by efflux of AEDs mainly at blood brain barrier BBB level. However, repetitive seizures can produce both brain and heart P-gp overexpression. Because P-gp activity induces membrane depolarization, its neuronal expression could be acting in the intrinsic mechanism of epileptogenesis, and its heart expression, can be a high risk factor of death, after severe-continuo convulsive stresses as in fatal status epilepticus or in SUDEP. Additionally, because P-gp is also a stem cell marker, we suggests that its constitutive overexpression in dysplastic neurons from brain epileptogenic areas observed in patients with refractory epilepsies, should be addressed as a risk factor of seizures relapse after surgical treatment. Here we discuss these concepts, based on our own clinical and experimental experiences, and reviewing the current literature on these subjects.

P-glycoprotein; membrane depolarization; drug resistance; SUDEP, biomarker, long-term relapse



Author: Alberto Lazarowski - ; INFIBIOC, FFyB-University of Buenos Aires UBA, Junin 956 1113, CABA, Argentina Liliana Czornyj - ; Fundaci

Source: http://hrcak.srce.hr/



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