Effects of levetiracetam, a novel antiepileptic drug, on convulsant activity in two genetic rat models of epilepsy.
The anticonvulsant effects of levetiracetam were assessed in two genetic rat models. In the audiogenic-seizure prone rat, levetiracetam, 5.4 to 96 mg/kg i.p. dose-dependently inhibited both wild running and tonic-clonic convulsions. In the GAERS model of petit mal epilepsy, levetiracetam markedly suppressed spontaneous spike-and-wave discharge (SWD) but left the underlying EEG trace normal. The effects were already marked at 5.4 mg/kg and did not increase significantly up to 170 mg/kg although more animals were completely protected. Levetiracetam produced no observable effects on behaviour apart from slight reversible sedation at 170 mg/kg. In contrast, piracetam, a structural analogue of levetiracetam, significantly and consistently suppressed SWD in GAERS rats only at the high dose of 1000 mg/kg with some slight effects at lower doses. The effect of piracetam appeared to be due to increased sleeping rather than to a direct antiepileptic effect. The results with levetiracetam argue for a clinical application in both petit mal, absence epilepsy and in treating generalised tonic-clonic and partial seizures.
Gower
A J
AJ
UCB S.A., Pharma Sector, Braine l'Alleud, Belgium.
Hirsch
E
E
Boehrer
A
A
Noyer
M
M
Marescaux
C
C
D000161:Acoustic Stimulation; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects; D004828:Epilepsies, Partial / Q000188:drug therapy; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D004832:Epilepsy, Absence / Q000188:drug therapy; D004830:Epilepsy, Tonic-Clonic / Q000188:drug therapy; D005260:Female; D000077287:Levetiracetam; D008297:Male; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar
D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam