Rat models of genetic absence epilepsy: what do EEG spike-wave discharges tell us about drug effects?
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.
van Luijtelaar
E L J M
EL
NICI, Department of Biological Psychology, University of Nijmegen, The Netherlands. g.vanluijtelaar@nici.kun.nl
Drinkenburg
W H I M
WH
van Rijn
C M
CM
Coenen
A M L
AM
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000187:drug effects* / Q000379:methods; D004832:Epilepsy, Absence / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D051381:Rats
D000927:Anticonvulsants