New developments in the search for improved antiepileptic drugs

Recent advances in neurobiology have yielded clues about the abnormal physiology of epilepsy and a better understanding of the action of the established anticonvulsants, which were discovered fortuitously or in animal screening tests. Some newer antiepileptic drugs may represent an important improvement over existing therapy, especially if they show efficacy in patients with intractable seizures or fewer limiting neurological side effects. Many developmental agents are designed to interact with a specific target and employ one of three strategies: enhancement of central inhibition; diminution of central excitation; or modulation of ionic channels regulating neuronal excitability. This article reviews the anticonvulsant compounds in development, with a focus on those being investigated in man. Updated information is also provided about the mechanisms of action of the antiepileptic drugs presently used as first line therapy.