Resistance to antiepileptic drugs (AED) remains a major problem in clinical epileptology.
This pharmacoresistance is independent of the choice of AEDs. Different hypotheses
have been proposed to explain the neurobiological basis for pharmacoresistance in
epilepsy. The transporter hypothesis is the mostly investigated theory. Hereby, overexpression
of multidrug efflux transporters, such as P-glycoprotein (Pgp), at the blood-brain-barrier
(BBB) is thought to be involved in pharmacoresistance in epilepsy by extruding AEDs from
their target site. Accumulating evidence supports an overexpression of Pgp in pharmacoresistant
epilepsy. Molecular Imaging studies provide unique opportunities for the in-vivo
study of the transporter hypothesis in the central nervous system (CNS). Several studies
demonstrated that positron emission tomography (PET) with [11C]-radiolabled Pgp substrates
is a promising tool for in vivo investigation of Pgp function at the rat, monkey and
human BBB. Quantification of Pgp over activity in epilepsy patients by in vivo imaging
could be highly useful because altered treatment strategies or novel AED could then be applied.
Keywords: Blood-brain-barrier, P-glycoprotein, positron emission tomography, drug transporter, epilepsy.
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