Department of Neonatal-Perinatal Medicine, MedStar Georgetown University Hospital, 3800 Reservoir Road NW, Washington, DC, 20007, USA.
Pharmacology and Physiology, Georgetown University, New Research Building W209B, Washington, DC, 20057, USA.
Pharmacol Rep. 2021 Feb;73(1):296-302. doi: 10.1007/s43440-020-00189-w. Epub 2020 Nov 18.
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.
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.
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.
These data indicate that while the efficacy of these drugs may be limited for neonatal seizures, their efficacy increases over early postnatal development.
常用于治疗新生儿癫痫的一线和二线抗癫痫药物疗效不佳。因此，作用机制不同于这些典型药物的药物可能提供更好的癫痫控制。AMPA 受体拮抗剂吡仑帕奈和 SV2A 配体布瓦西坦可能具有这种作用。
我们利用甲基-6,7-二甲氧基-4-乙基-β-咔啉-3-羧酸（DMCM）在大鼠中诱发癫痫，以评估吡仑帕奈和布瓦西坦在临床相关剂量下的疗效。
在出生后第 10 天（P10）的大鼠中，吡仑帕奈和布瓦西坦均不能抑制癫痫发作。相比之下，在 P21 大鼠中，两种药物均降低了癫痫发作的严重程度。在布瓦西坦 20 和 40mg/kg 剂量以及吡仑帕奈 0.9 和 2.7mg/kg 剂量下均观察到这种作用。
这些数据表明，虽然这些药物对新生儿癫痫的疗效可能有限，但它们的疗效在出生后早期会增加。
