PT  - JOURNAL ARTICLE
AU  - Wolfgang Löscher
AU  - Dagmar Hönack
AU  - Chris Rundfeldt
TI  - Antiepileptogenic Effects of the Novel Anticonvulsant Levetiracetam (ucb L059) in the Kindling Model of Temporal Lobe Epilepsy
DP  - 1998 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 474--479
VI  - 284
IP  - 2
4099  - http://jpet.aspetjournals.org/content/284/2/474.short
4100  - http://jpet.aspetjournals.org/content/284/2/474.full
SO  - J Pharmacol Exp Ther1998 Feb 01; 284
AB  - We have previously shown that the novel anticonvulsant levetiracetam exerts potent anticonvulsant activity against both focal and secondarily generalized seizures in fully amygdala-kindled rats,i.e., a model of temporal lobe epilepsy. We examined whether levetiracetam also exhibits antiepileptogenic activity,i.e., prevents or retards acquisition or development of amygdala-kindling in rats. Before the experiments with chronic administration of levetiracetam at different doses, we determined the pharmacokinetics of the drug after i.p. injection. Levetiracetam had a relatively short half-life (about 2-3 hr) in rats, so that any lasting effects of the drug after chronic administration were certainly not due to drug accumulation. When rats were treated with levetiracetam during kindling acquisition at daily i.p. doses of 13, 27 or 54 mg/kg, the drug dose-dependently suppressed the increase in seizure severity and duration induced by repeated amygdala stimulation. After termination of daily treatment with 54 mg/kg, duration of behavioral seizures and of afterdischarges recorded from the amygdala remained to be significantly shorter compared to vehicle controls, although amygdala stimulations were continued in the absence of drug. These data thus indicate that levetiracetam not simply masked the expression of kindled seizures through an anticonvulsant action, but exerted a true antiepileptogenic effect. Adverse effects were not observed at any dose of levetiracetam tested in kindled rats. The powerful antiepileptogenic activity of levetiracetam in the kindling model indicates that levetiracetam is not only an interesting novel drug for symptomatic treatment of epilepsy but might be suited for pharmacological prevention of this disease in patients with a high prospective risk of the development of epilepsy. The American Society for Pharmacology and Experimental Therapeutics