Anticonvulsant and acute neurotoxic effects of imperatorin, osthole and valproate in the maximal electroshock seizure and chimney tests in mice: A comparative study
Anticonvulsant and acute neurotoxic effects of imperatorin, osthole and valproate in the maximal electroshock seizure and chimney tests in mice: A comparative study
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DOI：
10.1016/j.eplepsyres.2009.03.027
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发表时间：
2009-08-01
影响因子：
2.2
通讯作者：
Czuczwar, Stanislaw J.
中科院分区：
文献类型：
--
作者：
Luszczki, Jarogniew J.;Wojda, Ewa;Czuczwar, Stanislaw J.
本研究的目的是在小鼠最大电休克发作和烟囱试验中确定并比较欧前胡素和蛇床子素（两种天然香豆素衍生物）与丙戊酸盐（一种经典抗癫痫药物）的抗惊厥和急性不良（神经毒性）作用。观察欧前胡素、蛇床子素和丙戊酸钠全身给药后15、30、60和120 min的抗惊厥作用和急性不良反应。局在最大电休克癫痫发作试验中对欧前胡素、蛇床子素和丙戊酸盐的时间-过程和剂量-反应关系的评价表明，这些化合物在小鼠中产生了明确的抗电休克作用，实验得出的欧前胡素的艾德（50）值范围为167 - 290 mg/kg，蛇床子素的范围为253 - 639 mg/kg，而丙戊酸盐的艾德（50）值范围为189 - 255 mg/kg。烟囱试验中急性神经毒性效应的评价显示，欧前胡素的TD（50）值范围为329 - 443 mg/kg，蛇床子素的TD（50）值范围为531 - 648 mg/kg，而丙戊酸盐的TD（50）值范围为363 - 512 mg/kg。欧前胡素的保护指数（TD（50）和艾德（50）值的比值）范围为1.13 - 2.60，蛇床子素的保护指数范围为0.83 - 2.44，丙戊酸盐的保护指数范围为1.72 - 2.00。总之，从临床前的角度来看，这两种天然香豆素衍生物都值得更多关注，因为这些化合物在抑制癫痫发作方面具有一些潜在的有利活性，与丙戊酸盐报告的活性非常相似。(C)2009 Elsevier B.V.保留所有权利。
The aim of this study was to determine and compare the anticonvulsant and acute adverse (neurotoxic) effects of imperatorin and osthole (two natural coumarin derivatives) with valproate (a classical antiepileptic drug) in the maximal electroshock seizure and chimney tests in mice. The anticonvulsant and acute adverse effects of imperatorin, osthole and valproate were determined at 15, 30, 60 and 120 min after their systemic (i.p.) administration. The evaluation of time-course and dose-response relationships for imperatorin, osthole and valproate in the maximal, etectroshock seizure test revealed that the compounds produced a clear-cut antielectroshock action in mice and the experimentally derived ED(50) values for imperatorin ranged between 167 and 290 mg/kg, those for osthole ranged from 253 to 639 mg/kg, whereas the ED(50) values for valproate ranged from 189 to 255 mg/kg. The evaluation of acute neurotoxic effects in the chimney test revealed that the TD(50) values for imperatorin ranged between 329 and 443 mg/kg, the TD(50) values for osthole ranged from 531 to 648 mg/kg, white the TD(50) values for valproate ranged from 363 to 512 mg/kg. The protective index (as a ratio of TD(50) and ED(50) values) for imperatorin ranged between 1.13 and 2.60, for osthole ranged from 0.83 to 2.44, and for valproate ranged between 1.72 and 2.00. In conclusion, both natural coumarin derivatives deserve more attention from a preclinical point of view as compounds possessing some potentially favorable activities in terms of suppression of seizures, quite similar to those reported for valproate. (C) 2009 Elsevier B.V. All rights reserved.