Novel antiseizure drug mechanisms

Abstract

The amount of new knowledge being generated regarding brain mechanisms in general, and epileptic mechanisms in particular, is enormous. Anticonvulsant drugs are ineffective in approximately a third of people with epilepsy. To our knowledge, strategies for preventing epilepsy after an initial insult are nonexistent. In this review, we briefly examine some recent novel concepts for preventing seizures, which might lead to enhanced anticonvulsant drug therapy. We start with some known seizure mechanisms that have yet to yield widely used anticonvulsant drugs, including potassium channels, chloride cotransporters, extracellular space constriction, gap junctions and magnesium. Pharmacoresistance is then discussed, focusing on the upregulation of drug-resistance proteins (a concept with significant therapeutic appeal) and the drug-target hypothesis. Two further areas that hold great promise for future therapeutics are sex hormones and inflammatory processes. The genetics of epilepsy are currently being elaborated, providing potential novel anticonvulsant targets. Prevention being better than a cure, we discuss epileptogenesis and its treatment. Given the astounding progress of neuroscience research, one hopes for many new therapeutics for our intractable epileptic patients.