Discovery of antiepileptic drugs.

Since 1993, the Anticonvulsant Drug Development Program has contributed to the successful development of nine clinically effective drugs for the symptomatic treatment of epilepsy. These include felbamate (1993), gabapentin (1994), lamotrigine (1994), fosphenytoin (1996), topiramate (1996), tiagabine (1997), levetiracetam (1999), zonisamide (2000), and oxcarbazepine (2000). Despite the apparent success of the current discovery process, a significant need persists for more efficacious and less toxic antiepileptic drugs (AEDs). This is particularly true for patients whose seizures remain refractory to the currently available AEDs. This chapter will review the current process for AED discovery employed by the Anticonvulsant Drug Development Program at the University of Utah and other laboratories working toward the common goal of discovering better therapeutic options for patients living with epilepsy. It will discuss some of the inherent advantages and limitations of the primary animal models employed, while offering insight into potential future directions as we seek to better understand the pathophysiology underlying acquired epilepsy, therapy resistance, and epileptogenesis.