Animal models used in the screening of antiepileptic drugs

Abstract

The identification of potential therapeutic agents for the treatment of epilepsy requires the use of seizure models. These models can be either in vivo or in vitro, mechanism specific, mechanism independent, or seizure specific. To be predictive of therapeutic activity in patients, the models should approximate the events that precipitate seizures in humans. Model validation is defined by determining the pharmacologic characteristics using known clinically effective drugs. Mechanism-independent models were used to identify the first antiepileptic drugs [AEDs; e.g., phenobarbital (PB) and phenytoin (PHT)]. Mechanism-specific models are based on the fundamental process by which seizure propagation and inhibition occurs. Seizure-type models identify a compound's potential based on its effects on electrographic and behavioral response. No single model can be used to identify potential compounds adequately for development. The full pharmacologic-anticonvulsant profile of a potentially useful new therapeutic agent is required to ensure successful development.