Effects of lamotrigine and levetiracetam on seizure development in a rat amygdala kindling model.
In kindling models of epilepsy, the period during which repeated stimulation evokes intensifying seizures is attributed to an underlying epileptogenic process, and the point at which class 5 kindled seizures occur is considered the established epileptic state. Previous studies have indicated that a separation can occur between drug effects on these two components. For example, carbamazepine and phenytoin inhibit kindled seizures but have no effect on seizure development, whereas levetiracetam inhibits both components. We have investigated the profile of lamotrigine in the amygdala kindling model, including levetiracetam for comparison. As expected, both treatments dose-dependently inhibited class 5 kindled seizures. In a separate study, daily administration of either lamotrigine (20mgkg(-1) i.p.) or levetiracetam (50mgkg(-1) i.p.) demonstrated antiepileptogenic-like effects by blocking seizure development during the treatment period. Following cessation of drug treatment, further daily stimulation resulted in kindled seizure development, though there was a significant increase with both treatment groups, relative to the control group, in the total number of stimulations required to produce classes 3 and 5 seizures. In addition, prior levetiracetam treatment appeared to delay or prevent the expected increase in after-discharge duration (ADD). These results suggest that lamotrigine, like levetiracetam, possesses the ability to counteract kindling acquisition, which differentiates it from other drugs with sodium channel blocking activity.
Stratton
Sharon C
SC
Neurology and GI Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, CM19 5AW, Essex, UK. sharon.c.stratton@gsk.com
Large
Charles H
CH
Cox
Brian
B
Davies
Gary
G
Hagan
Russell M
RM
D000679:Amygdala / Q000502:physiology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D007696:Kindling, Neurologic; D000077213:Lamotrigine; D000077287:Levetiracetam; D008297:Male; D008959:Models, Neurological; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D012640:Seizures / Q000145:classification / Q000517:prevention & control*; D014227:Triazines / Q000494:pharmacology*
D000927:Anticonvulsants; D014227:Triazines; D000077287:Levetiracetam; D000077213:Lamotrigine; D010889:Piracetam