Electroencephalographic studies in the WAG/Rij rats of Nijmegen and genetic absence epileptic rats of Strasbourg (GAERS), two genetic models for human generalized
absence epilepsy, illustrate the usefulness of
drug-electroencephalogram (EEG) interaction studies. In the EEG of both types of rats, spontaneously occurring spike-wave discharges are present. For
drug discovery, a model with predictive validity is imperative, and both the WAG/Rij and the GAERS models seem adequate. The present paper discusses effects on spike-wave discharges of various compounds that are clinically used. Not only new
antiepileptic drugs, such as
remacemide,
loreclezole,
lamotrigine,
tiagabine,
gabapentin,
progabide and
levetiracetam are evaluated, but also drugs used for other purposes, such as
etomidate and
fentanyl-
fluanisone for
anesthesia, opioidergic drugs and drugs used for
strokes. It is shown that some new
antiepileptic drugs, such as
tiagabine, have spike-wave discharge-increasing properties, while other drugs are worth studying in clinical trials for antiabsence treatment. Furthermore, it is shown that many commonly used drugs such as
analgesics,
anesthetics and drugs to treat
stroke generally enhance spike-wave discharges. It can be concluded that EEG monitoring is imperative for the discovery and development of potentially
antiepileptic compounds and that genetic rat models such as the WAG/Rij or GAERS, to a large extent, can reliably predict clinical efficacy of various types of compounds as well as alert us of potentially adverse effects.