Preclinical development of antiepileptic drugs: past, present, and future directions.

摘要: Summary:  Since 1993, nine new antiepileptic drugs (AEDs) have been introduced into the U.S. market for symptomatic treatment of partial epilepsy. Their activity was, most part, defined by acute seizure models such as maximal electroshock (MES) and subcutaneous pentylenetetrazol (scPTZ) tests kindled rat. Unfortunately, clinical evidence to date would suggest that none these models, albeit useful, are likely identify those therapeutics will effectively manage patient with refractory seizures. In recent years, a number in vivo vitro developed display varying degrees pharmacoresistance. As such, they may provide unique opportunity identifying truly novel AED. Through greater understanding pathophysiology acquired epilepsy at molecular genetic level, it be possible therapeutic approach reaches beyond modify progression, or, dare we suggest, prevent development susceptible patient. The realization possibility necessitate change our current AED discovery approach. present review describes used search AEDs offers some insight future directions incorporating emerging therapy resistance epileptogenesis.