Drug-Resistant Epilepsy: drug target hypothesis and beyond the receptors.

Epilepsy is a chronic neurological disorder that affects over 70 million people worldwide. Despite a recent introduction of antiseizure drugs for the treatment of epileptic seizures, one-third of these patients suffer from drug-resistant epilepsy (DRE). The therapeutic target hypothesis is a cited theory to explain DRE. According to the target hypothesis, the failure to achieve seizure freedom leads to alteration of the structure and/or function of the antiseizure medication target. However, this hypothesis fails to explain why DRE patients do not respond to anti-seizure medications of different targets. This review presents different conditions, such as epigenetic mechanisms and protein-protein interactions that may result in alterations of diverse drug targets using different mechanisms. These novel conditions represent new targets to control DRE.