Marko Culjat1,2, Megan N Huizenga2, Patrick A Forcelli3,4,5. 1. Department of Neonatal-Perinatal Medicine, MedStar Georgetown University Hospital, 3800 Reservoir Road NW, Washington, DC, 20007, USA. 2. Pharmacology and Physiology, Georgetown University, New Research Building W209B, Washington, DC, 20057, USA. 3. Pharmacology and Physiology, Georgetown University, New Research Building W209B, Washington, DC, 20057, USA. paf22@georgetown.edu. 4. Neuroscience, Georgetown University, Washington, DC, USA. paf22@georgetown.edu. 5. Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC, USA. paf22@georgetown.edu.
Abstract
BACKGROUND: The antiseizure drugs commonly used as first- and second-line treatments for neonatal seizures display poor efficacy. Thus, drug mechanisms of action that differ from these typical agents might provide better seizure control. Perampanel, an AMPA-receptor antagonist, and brivaracetam, a SV2A ligand, might fill that role. METHODS: We utilized methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) to evoke seizures in rats to assess the efficacy of perampanel and brivaracetam treatment in clinically relevant doses. RESULTS: In postnatal day (P)10 rats, neither perampanel nor brivaracetam suppressed seizure activity. By contrast, in P21 rats, both drugs decreased the severity of seizures. This effect was evident at the 20 and 40 mg/kg doses of brivaracetam and at the 0.9 and 2.7 mg/kg doses of perampanel. CONCLUSIONS: These data indicate that while the efficacy of these drugs may be limited for neonatal seizures, their efficacy increases over early postnatal development.
BACKGROUND: The antiseizure drugs commonly used as first- and second-line treatments for neonatal seizures display poor efficacy. Thus, drug mechanisms of action that differ from these typical agents might provide better seizure control. Perampanel, an AMPA-receptor antagonist, and brivaracetam, a SV2A ligand, might fill that role. METHODS: We utilized methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) to evoke seizures in rats to assess the efficacy of perampanel and brivaracetam treatment in clinically relevant doses. RESULTS: In postnatal day (P)10 rats, neither perampanel nor brivaracetam suppressed seizure activity. By contrast, in P21 rats, both drugs decreased the severity of seizures. This effect was evident at the 20 and 40 mg/kg doses of brivaracetam and at the 0.9 and 2.7 mg/kg doses of perampanel. CONCLUSIONS: These data indicate that while the efficacy of these drugs may be limited for neonatal seizures, their efficacy increases over early postnatal development.
Authors: Henrik Klitgaard; Alain Matagne; Jean-Marie Nicolas; Michel Gillard; Yves Lamberty; Marc De Ryck; Rafal M Kaminski; Karine Leclercq; Isabelle Niespodziany; Christian Wolff; Martyn Wood; Jonas Hannestad; Sophie Kervyn; Benoit Kenda Journal: Epilepsia Date: 2016-02-26 Impact factor: 5.864
Authors: M J Painter; M S Scher; A D Stein; S Armatti; Z Wang; J C Gardiner; N Paneth; B Minnigh; J Alvin Journal: N Engl J Med Date: 1999-08-12 Impact factor: 91.245