Is the persistent sodium current a specific target of anti-absence drugs?
The persistent Na+ current (INaP) has been proposed as the putative target of the anti-absence antiepileptic drugs. Accordingly, the effect of reference anti-absence drugs ethosuximide (ESM) and valproate (VPA), and of the new antiepileptic drug levetiracetam (LEV), on INaP have been tested in CA1 hippocampal neurons and compared to the classic anticonvulsant phenytoin (PHT) and the neuroprotective agent riluzole (RIL). Whole-cell patch-clamp recordings of the slowly inactivating current, fully characterized as INaP, were performed with a standard voltage-step protocol on thin hippocampal slices prepared from rat brain. Both PHT (100 microM) and RIL (10 microM) strongly depressed INaP, whereas ESM (1 mM) induced a slight decrease of INaP and VPA (1 mM) had no effect. Likewise, 60-min perfusion with relevant concentrations of LEV (10, 32 or 100 microM) did not modify INaP. In conclusion, these data question the impact of INaP depression as an anti-absence mechanism, and also disclaim the involvement of INaP in the antiepileptic mechanism of LEV.
Niespodziany
Isabelle
I
UCB S.A. Pharma Sector, Preclinical CNS Research, Chemin du Foriest, B-1420 Braine-l'Alleud, Belgium. Isabelle.Niespodziany@UCB-Group.com
Klitgaard
Henrik
H
Margineanu
Doru Georg
DG
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008297:Male; D051381:Rats; D015222:Sodium Channels / Q000502:physiology*
D000927:Anticonvulsants; D015222:Sodium Channels