The acute and chronic effects of the novel anticonvulsant lacosamide in an experimental model of status epilepticus

• Published in: Epilepsy research Vol. 94; no. 1; pp. 10 - 17
• Main Authors: Wasterlain, Claude G, Stöhr, Thomas, Matagne, Alain
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-03-2011
• Subjects: Acetamides - therapeutic use; Analysis of Variance; Animals; Anticonvulsants - therapeutic use; Antiepileptic drug; Disease Models, Animal; Dose-Response Relationship, Drug; Electroencephalography; Lacosamide; Neurology; Perforant pathway Stimulation; Rat; Rats; Self Administration; Spontaneous recurrent seizures; Status epilepticus; Status Epilepticus - drug therapy; Status Epilepticus - physiopathology; Time Factors; Antiepileptic drug; Perforant pathway Stimulation; Rat; Spontaneous recurrent seizures; Status epilepticus; Lacosamide
• ISSN: 0920-1211; 1872-6844
• DOI: 10.1016/j.eplepsyres.2010.12.014

Summary The effective management of status epilepticus (SE) continues to be a therapeutic challenge. The aim of this study was to investigate the efficacy of lacosamide treatment in an experimental model of self-sustaining SE. Rats were treated with lacosamide (3, 10, 30 or 50 mg/kg) either 10 min (early treatment) or 40 min (late treatment) after the initiation of perforant path stimulation. Early lacosamide treatment significantly and dose-dependently reduced acute SE seizure activity; late treatment showed only a non-significant trend toward reduced seizure activity. Early lacosamide treatment also dose-dependently reduced the number of spontaneous recurrent seizures following a 6-week waiting period, with 70% reduction at the highest dose tested (50 mg/kg); there was also a significant reduction in the number of spikes and the cumulative time spent in seizures. Late treatment with high-dose lacosamide (30–50 mg/kg) reduced the number of animals that developed spontaneous recurrent seizures (33% vs 100% in controls, P < .05), but did not significantly reduce seizure severity or frequency in rats that developed spontaneous recurrent seizures. The results presented here suggest that lacosamide deserves investigation for the clinical treatment of SE. Potential for disease modification in this rat model of self-sustaining SE will require further studies.