Abstract
Although several new antiepileptic drugs (AEDs) have been launched during the last two decades, pharmacoresistance of epilepsy is still a major problem in clinical neurology. About 30% of all epileptic patients do not adequately respond to drug treatment.1 In adults, temporal lobe epilepsy (TLE) with complex-partial seizures has the poorest prognosis with up to 70% of the patients being resistant to treatment with available AEDs.2 Although several risk factors for intractability have been identified, the mechanisms underlying intractable epilepsy have not been fully enlightened. Recent data gave evidence that pharmacodynamic mechanisms, i.e., changes in drug targets (target hypothesis),3 as well as pharmacokinetic mechanisms, i.e., a local decrease in brain access of AEDs mediated by overexpression of multidrug transporters (multidrug transporter hypothesis),4 may be involved. Investigations in animal models of pharmacoresistant epilepsy are helpful to increase the understanding of the underlying basis of intractability, i.e., to further substantiate the existing hypotheses, to define further mechanisms, and to examine how different mechanisms coact. Unfortunately, there are only few animal models of pharmacoresistant epilepsy. One of the most extensively characterized animal models in this respect is a pharmacoresistant subgroup of amygdala-kindled Wistar rats.
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Potschka, H., Löscher, W. (2005). Mechanisms of Pharmacoresistance in the Phenytoin-Resistant Kindled Wistar Rat. In: Corcoran, M.E., Moshé, S.L. (eds) Kindling 6. Advances in Behavioral Biology, vol 55. Springer, Boston, MA. https://doi.org/10.1007/0-387-26144-3_31
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DOI: https://doi.org/10.1007/0-387-26144-3_31
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