Age-dependent anticonvulsant actions of perampanel and brivaracetam in the methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) model of seizures in developing rats
| Autor: | Marko Culjat, Patrick A. Forcelli, Megan N. Huizenga |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Drug
Aging Pyridones medicine.medical_treatment media_common.quotation_subject Convulsants Pharmacology Brivaracetam Article Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Perampanel 0302 clinical medicine Seizures DMCM Nitriles medicine Animals Neonatal seizure media_common SV2A business.industry Antagonist General Medicine Pyrrolidinones Rats Anticonvulsant chemistry 030220 oncology & carcinogenesis Anticonvulsants Female business 030217 neurology & neurosurgery Carbolines medicine.drug |
| Zdroj: | Pharmacol Rep |
| ISSN: | 2299-5684 1734-1140 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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