On the Development of New Antiepileptic Drugs for the Treatment of Pharmacoresistant Epilepsy: Different Approaches to Different Hypothesis

Abstract

Despite the introduction of 15 new antiepileptic drugs to the market since 1990, around a third of the epileptic patients do not achieve seizure remission with current known medications. The chapter overviews current hypothesis on the causes of drug resistant epilepsy, with an emphasis on the most documented explanations. On the basis of those hypotheses, current approaches to the development of novel antiepileptic medications are overviewed, including adjuvant Pgp-inhibitors, development of Pgp-non substrates, use of nanocarriers to circumvent active transport, design of multi-target directed ligands and adjuvant therapies with antioxidant and anti-inflammatory medications. In line with current discussions on the matter, it is proposed that different hypothesis may serve as explanation for different subgroups of drug-resistant patients, and that—in the light of recent basic research—at least some of the hypotheses may be interrelated.