Choosing the Correct Antiepileptic Drugs: From Animal Studies to the Clinic

Epilepsy is a chronic condition caused by an imbalance of normal excitatory and inhibitory forces in the brain. Antiepileptic drug therapy is directed primarily toward reducing excitability through blockage of voltage-gated Na⁺ or Ca²⁺ channels, or increasing inhibition through enhancement of γ-aminobutyric acid currents. Prior to clinical studies, putative antiepileptic drugs are screened in animals (usually rodents). Maximal electrical shock, pentylenetetrazol, and kindling are typically used as nonmechanistic screens for antiseizure properties, and the rotorod test assesses acute toxicity. Whereas antiseizure drug screening has been successful in bringing drugs to the market and improving our understanding of the pathophysiology of seizures, it merits emphasis that the vast majority of drug screening occurs in mature male rodents and involves models of seizures, not epilepsy. Effective drugs in acute seizures may not be effective in chronic models of epilepsy. Seizure type, clinical and electroencephalographic phenotype, syndrome, and etiology are often quite different in children with epilepsy than in adults. Despite these age-related unique features, drugs used in children are generally the same as those in adults. As awareness of the unique features of seizures during development increases, more drug screening in the immature animal will likely occur.