Perampanel, a potent AMPA receptor antagonist, protects against tetramethylenedisulfotetramine-induced seizures and lethality in mice: comparison with diazepam.
Perampanel, a potent AMPA receptor antagonist, protects against tetramethylenedisulfotetramine-induced seizures and lethality in mice: comparison with diazepam.
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DOI：
10.1007/s00204-021-03053-9
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发表时间：
2021-07
影响因子：
6.1
通讯作者：
Rogawski MA
中科院分区：
文献类型：
--
作者：
Zolkowska D;Dhir A;Rogawski MA
Tetramethylenedisulfotetramine (TETS), a noncompetitive GABAA receptor antagonist, is a potent, highly lethal convulsant that is considered to be a chemical threat agent. Here, we assessed the ability of the AMPA receptor antagonist perampanel to protect against TETS-induced seizures and lethality in mice when administered before or after treatment with the toxicant. For comparison, we conducted parallel testing with diazepam, which is a first-line treatment for chemically induced seizures in humans. Pre-treatment of mice with either perampanel (1–4 mg/kg, i.p.) or diazepam (1–5 mg/kg, i.p.) conferred protection in a dose-dependent fashion against tonic seizures and lethality following a dose of TETS (0.2 mg/kg, i.p.) that rapidly induces seizures and death. The ED50 values for protection against mortality were 1.6 mg/kg for perampanel and 2.1 mg/kg for diazepam. Clonic seizures were unaffected by perampanel and only prevented in a minority of animals by high-dose diazepam. Neither treatment prevented myoclonic body twitches. Perampanel and diazepam also conferred protection against tonic seizures and lethality when administered 15 min following a 0.14 mg/kg, i.p., dose of TETS and 5 min following a 0.2 mg/kg, i.p., dose of TETS. Both posttreatments were highly potent at reducing tonic seizures and lethality in animals exposed to the lower dose of TETS whereas greater doses of both treatments were required in animals exposed to the larger dose of TETS. Neither treatment was as effective suppressing clonic seizures. In an experiment where 0.4 mg/kg TETS was administered by oral gavage and the treatment drugs were administered 5 min later, perampanel only partially protected against lethality whereas diazepam produced nearly complete protection. We conclude that perampanel and diazepam protect against TETS-induced tonic seizures and lethality but have less impact on clonic seizures. Both drugs could have utility in the treatment of TETS intoxication but neither eliminates all seizure activity.
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DOI：
10.1111/ane.12099
发表时间：
2013
期刊：
Acta neurologica Scandinavica. Supplementum
影响因子：
--
作者：
Rogawski MA
通讯作者：
Rogawski MA
地西ep剂的暴露后给药结合可溶性环氧化物水解酶抑制作用，可停止癫痫发作，并在急性TET中毒的鼠模型中调节神经炎症。
影响因子：
3.8
作者：
Vito, Stephen T.;Austin, Adam T.;Banks, Christopher N.;Inceoglu, Bora;Bruun, Donald A.;Zolkowska, Dorota;Tancredi, Daniel J.;Rogawski, Michael A.;Hammock, Bruce D.;Lein, Pamela J.
通讯作者：
Lein, Pamela J.
影响因子：
4.7
作者：
Twele, Friederike;Bankstahl, Marion;Loescher, Wolfgang
通讯作者：
Loescher, Wolfgang
影响因子：
2.6
作者：
Hanada, Takahisa;Ido, Katsutoshi;Kosasa, Takashi
通讯作者：
Kosasa, Takashi
影响因子：
3.4
作者：
Moffett, Mark C.;Rauscher, Noah A.;Myers, Todd M.
通讯作者：
Myers, Todd M.