Intramuscular atenolol and levetiracetam reduce mortality in a rat model of paraoxon-induced status epilepticus.
Intramuscular atenolol and levetiracetam reduce mortality in a rat model of paraoxon-induced status epilepticus.
复制标题
DOI：
10.1111/nyas.14500
复制
发表时间：
2020-11
影响因子：
5.2
通讯作者：
DeLorenzo RJ
中科院分区：
文献类型：
--
作者：
Deshpande LS;Blair RE;Halquist M;Kosmider L;DeLorenzo RJ
有机磷 (OP) 化合物是化学威胁剂，是乙酰胆碱酯酶的不可逆抑制剂，可导致高胆碱能反应，包括癫痫持续状态 (SE)。 SE 特别针对心脏和大脑，尽管有现有的治疗方法，但它仍然与显着的死亡率和发病率相关。在这里，我们研究了在对氧磷 (POX) 诱导 SE 后施用由阿替洛尔 (AT) 和左乙拉西坦 (LV) 组成的肌内 (i.m.) 辅助治疗的效果。联合疗法每日两次，持续 2、7 或 14 天。大鼠暴露于 POX 后会导致快速 SE 发作，并用阿托品、解磷定和咪达唑仑进行治疗。在这里，AT + LV 疗法显着降低了 SE 后 30 天评估的 POX SE 死亡率。 AT + LV 治疗表现出的肌肉病理炎症评分与盐水治疗的对照组没有显着差异。药代动力学分析表明，肌肉注射。与口服给药相比，该途径在 OP SE 条件下实现了 AT 和 LV 更快、更稳定的血浆治疗水平。我们的数据提供了 i.m. 的安全性和有效性的证据。 AT + LV 疗法可降低 POX SE 后的死亡率。有机磷 (OP) 化合物是乙酰胆碱酯酶的不可逆抑制剂，可导致胆碱能亢进反应，包括癫痫持续状态 (SE)，其目标是心脏和大脑，并与显着的死亡率和发病率相关。在这里，我们研究了由 β-肾上腺素能阻滞剂阿替洛尔和抗癫痫药左乙拉西坦组成的肌内辅助治疗在大鼠模型中由 OP 化合物对氧磷诱导 SE 后给药的效果。
Organophosphorus (OP) compounds are chemical threat agents and are irreversible inhibitors of the enzyme acetylcholinesterase that lead to a hypercholinergic response that could include status epilepticus (SE). SE particularly targets the heart and the brain and despite existing therapies it is still associated with significant mortality and morbidity. Here, we investigated the effect of intramuscular (i.m.) adjunct therapy consisting of atenolol (AT) and levetiracetam (LV) when administered after paraoxon (POX)-induced SE. The combination therapy was administered twice daily for 2, 7, or 14 days. POX exposure in rats produced rapid SE onset that was treated with atropine, pralidoxime chloride, and midazolam. Here, AT + LV therapy produced significant reductions in POX SE mortality assessed at 30 days post SE. AT + LV therapy exhibited muscle pathology inflammation scores that were not significantly different from saline-treated controls. Pharmacokinetic analyses revealed that the i.m. route achieved faster and stabler plasma therapeutic levels for both AT and LV under OP SE conditions compared with oral administrations. Our data provides evidence of the safety and efficacy of i.m. AT + LV therapy for reducing mortality following POX SE. Organophosphorus (OP) compounds are irreversible inhibitors of the enzyme acetylcholinesterase that lead to a hypercholinergic response that includes status epilepticus (SE), which targets the heart and the brain and is associated with significant mortality and morbidity. Here, we investigated the effect of intramuscular adjunct therapy consisting of the β-adrenergic blocker atenolol and the antiepileptic drug levetiracetam when administered after SE induced by the OP compound paraoxon in a rat model.
登录
查看更多内容
影响因子：
2.2
作者：
Bealer, Steven L.;Little, Jason G.;Metcalf, Cameron S.;Brewster, Amy L.;Anderson, Anne E.
通讯作者：
Anderson, Anne E.
影响因子：
2.5
作者：
Blair RE;Deshpande LS;Holbert WH 2nd;Churn SB;DeLorenzo RJ
通讯作者：
DeLorenzo RJ
DOI：
10.14581/jer.17014
发表时间：
2017-12
期刊：
Journal of epilepsy research
影响因子：
--
作者：
Choudhary N;Deepak KK;Chandra PS;Bhatia S;Sagar R;Jaryal AK;Pandey RM;Tripathi M
通讯作者：
Tripathi M
影响因子：
3.8
作者：
Deshpande, Laxmikant S.;Carter, Dawn S.;DeLorenzo, Robert J.
通讯作者：
DeLorenzo, Robert J.
影响因子：
168.9
作者：
Eddleston, Michael;Buckley, Nick A.;Eyer, Peter;Dawson, Andrew H.
通讯作者：
Dawson, Andrew H.