title: The acute and chronic effects of the novel anticonvulsant lacosamide in an experimental model of status epilepticus.
abstract: 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 50mg/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 (50mg/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 (30-50mg/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.
authors.affiliation: Department of Neurology, and Brain Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90073, USA. wasterla@ucla.edu
authors.forename: Claude G
authors.initials: CG
authors.lastname: Wasterlain
authors.forename: Thomas
authors.initials: T
authors.lastname: Stöhr
authors.forename: Alain
authors.initials: A
authors.lastname: Matagne
mesh_terms: D000081:Acetamides / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D000078334:Lacosamide; D051381:Rats; D012646:Self Administration; D013226:Status Epilepticus / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D000078334:Lacosamide