Huperzine A suppresses absence seizures in the genetic absence epilepsy rat from Strasbourg (GAERS) model of genetic generalized epilepsy with absence seizures.
Autor: | Casillas-Espinosa PM; Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia.; Department of Neuroscience, School of Translational Medicine,, Monash University, Melbourne, Victoria, Australia.; Department of Neurology, The Alfred Hospital, Melbourne, Victoria, Australia., Garcia-Olivares J; Supernus Pharmaceuticals, Inc., Rockville, Maryland, USA., Li R; Department of Neuroscience, School of Translational Medicine,, Monash University, Melbourne, Victoria, Australia., Li C; Department of Neuroscience, School of Translational Medicine,, Monash University, Melbourne, Victoria, Australia., Yu C; Supernus Pharmaceuticals, Inc., Rockville, Maryland, USA., Formella AE; Supernus Pharmaceuticals, Inc., Rockville, Maryland, USA., O'Brien TJ; Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia.; Department of Neuroscience, School of Translational Medicine,, Monash University, Melbourne, Victoria, Australia.; Department of Neurology, The Alfred Hospital, Melbourne, Victoria, Australia. |
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Jazyk: | angličtina |
Zdroj: | Epilepsia open [Epilepsia Open] 2024 Oct; Vol. 9 (5), pp. 1826-1836. Date of Electronic Publication: 2024 Aug 03. |
DOI: | 10.1002/epi4.13016 |
Abstrakt: | Objective: We evaluated huperzine A treatment in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS) model of genetic generalized epilepsy (GGE) with absence seizures. Methods: Adult male GAERS (N = 15) were implanted with EEG recording electrodes 10 days before receiving study drug. Each animal received the following six treatments as a single, intraperitoneal dose, 7 days apart (in random order): huperzine A (0.3, 1.0, or 3.0 mg/kg), two periods of vehicle (0.9% NaCl), or ethosuximide (100 mg/kg) as a positive control. Electroencephalograms (EEGs) were acquired for 24 h before and after each treatment and analyzed for seizure activity during the 90-min period immediately post-treatment, including 30-min intervals at 30, 60, and 90 min. Additional analyses evaluated seizure activity over the 24-h post-treatment period using 60-min intervals at 6, 12, and 24 h. The cumulative 24-h periods before and after each administered treatment were also compared. Results: Two-way ANOVA showed a treatment difference [F Significance: Huperzine A potently suppressed absence-like seizures in GAERS, albeit with a shorter duration of action relative to ethosuximide, showing promise for clinical efficacy in GGE. Plain Language Summary: This study looked at how huperzine A affects seizures in rats with similar abnormal brain activity as seen in humans with absence epilepsy. Rats received different treatments, placebo (i.e., saline solution), huperzine A, and ethosuximide. Ethosuximide is considered a gold standard treatment for absence epilepsy. We recorded brain activity to measure seizures before and after each treatment. We found that huperzine A (3.0 mg/kg) reduced seizures soon after treatment, like ethosuximide. Both treatments appeared safe, causing only mild sleepiness. The study shows that huperzine A could be a good new treatment for a type of absence epilepsy. (© 2024 Supernus Pharmaceuticals, Inc. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.) |
Databáze: | MEDLINE |
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