Antiepileptic effects of single and repeated oral administrations of S-312-d, a novel calcium channel antagonist, on tonic convulsions in spontaneously epileptic rats
Antiepileptic effects of single and repeated oral administrations of S-312-d, a novel calcium channel antagonist, on tonic convulsions in spontaneously epileptic rats
复制标题
DOI：
10.1254/jphs.fp0040233
复制
发表时间：
2004-07-01
影响因子：
3.5
通讯作者：
Sakai, N
中科院分区：
文献类型：
--
作者：
Amano, T;Aihua, Z;Sakai, N
我们研究了S-312-d（甲基-4，7-二氢-3-异丁基-6-甲基-4-（3-硝基苯基）-噻吩并-[2，3-B]吡啶-5-羧酸酯）（一种新合成的L型钙通道阻滞剂）单次和重复给药对自发性癫痫大鼠（SER：zi/zi，tm/tm）（一种基于遗传的人类癫痫动物模型）强直性惊厥和失神样癫痫发作的影响。单次口服S-312-d可剂量依赖性地抑制强直性惊厥，作用持续2 h以上，但不能减弱失神样癫痫发作。我们还检查了重复给予1 mg/kg S-312-d（每天一次，持续4天）对SER的影响。首次给药后45和75 min分别观察到强直性惊厥次数和总持续时间显著减少。效果持续了24小时，没有改变背景脑电图或血压。随后每日给予S-312-d可逐渐加强对强直性惊厥的抑制作用，并在停止给药后持续3天。与此相反，S-312-d重复治疗不影响SER的失神样发作。这些结果表明，S-312-d是一种候选药物，对人类癫痫的惊厥发作具有抗癫痫作用。
We investigated the effects of single and repeated administrations of S-312-d (methyl-4,7-dihydro-3-isobutyl-6-methyl-4-(3-nitrophenyl)-thieno-[2,3-b]pyridine-5-carboxylate), a newly synthesized L-type Ca2+-channel blocker, on tonic convulsions and absence-like seizures in the spontaneously epileptic rat (SER: zi/zi, tm/tm), a genetically based animal model of human epilepsy. Single oral administrations of S-312-d dose-dependently inhibited tonic convulsions and the effects lasted for more than 2 h, although they did not attenuate the absence-like seizures. We also examined the effects of repeated administrations of S-312-d at I mg/kg once a day for 4 days on SER. A significant decrease in the number and total duration of tonic convulsions was observed 45 and 75 min after the first administration of the drug, respectively. The effects lasted for 24 h without changes in the background EEG or blood pressure. This inhibitory effect on the tonic convulsions was gradually strengthened by subsequent daily administrations of S-312-d and lasted for 3 days after the cessation of drug treatment. In contrast, the repeated treatment with S-312-d did not influence absence-like seizures of SER. These results suggest that S-312-d is a candidate drug that has antiepileptic effects against the convulsive seizures in human epilepsy.