Effects of the Novel Antiepileptic Drug Lacosamide on the Development of Amygdala Kindling in Rats

Authors


  • Present address of Anna Heile: International Neuroscience Institute (INI), Hannover, Germany.

Address correspondence and reprint requests to Dr. W. Löscher, Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Bünteweg 17, D-30559 Hannover, Germany. E-mail: wolfgang.loescher@tiho-hannover.de

Abstract

Summary: Purpose: The current treatment of epilepsy focuses exclusively on the prophylaxis or suppression of seizures and thus provides merely a symptomatic treatment, without clear influence on the course of the disease. There is a need for new drugs that act at different molecular targets than currently available antiepileptic drugs (AEDs) and for new therapies designed to block the process of epileptogenesis. In recent years, different research lines have examined the epileptogenic process in order to understand the different stages in this process, and with the hope that early recognition and intervention could prevent the development or progression of epilepsy. In animals, acquired epilepsy is studied most commonly with the kindling model and status epilepticus models. In the present study, we used the kindling model to evaluate whether the novel AED lacosamide affects kindling-induced epileptogenesis. This drug does not seem to act by any of the mechanisms of currently available AEDs, but the exact molecular mechanisms of action of lacosamide have not yet been clarified.

Methods: Groups of 9–10 rats were treated with either vehicle or different doses of lacosamide (3, 10, or 30 mg/kg/day) over 22–23 days during amygdala kindling.

Results: Daily administration of lacosamide during kindling acquisition produced a dose-dependent effect on kindling development. While the drug was inactive at 3 mg/kg/day, significant retardation of kindling was observed at 10 mg/kg/day, by which the average number of stimulations to reach kindling criterion was increased by >90%. A significant inhibitory effect on kindling acquisition was also observed with 30 mg/kg/day, but this dose of lacosamide was associated with adverse effects.

Conclusions: The present data demonstrate that lacosamide, in addition to exerting anticonvulsant activity, has the potential to retard kindling-induced epileptogenesis. Whether this indicates that lacosamide possesses antiepileptogenic or disease-modifying potential needs to be further evaluated, including studies in other models of acquired epilepsy.

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