Intracerebroventricular administration of histamine H3 receptor antagonists decreases seizures in rat models of epilepsia.
Intracerebroventricular administration of histamine H3 receptor antagonists decreases seizures in rat models of epilepsia.
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DOI：
10.1358/mf.2004.26.4.831331
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发表时间：
2004-05
影响因子：
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通讯作者：
Chie Harada;T. Hirai;Y. Fujii;S. Harusawa;T. Kurihara;C. Kamei
中科院分区：
文献类型：
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作者：
Chie Harada;T. Hirai;Y. Fujii;S. Harusawa;T. Kurihara;C. Kamei
本文研究了组胺H3受体拮抗剂对大鼠杏仁核点燃和最大电休克发作的影响，以确定其作为抗癫痫新药的潜力。在戊巴比妥麻醉下，将大鼠固定在立体定位装置上，并将用于给药的不锈钢引导套管植入侧脑室。在杏仁核点燃癫痫发作，电极被植入到右杏仁核和脑电图记录双极;刺激施加双极每天由恒流刺激器，并继续，直到获得全身性惊厥。在最大电休克（MES）发作试验中，通过耳夹电极刺激动物诱发电惊厥，并测量强直性和阵挛性发作的持续时间。硫代哌丁胺、氯苯丙哌、碘苯丙哌、VUF 5514、VUF 5515和VUF 4929对杏仁核点燃癫痫发作的发作期和后放电持续时间均有剂量依赖性抑制作用。H3受体拮抗剂可抑制MES诱发的强直性发作持续时间，但对阵挛性发作持续时间无影响。在所测试的H3拮抗剂中，clobenpropit和iodophenpropit分别比杏仁核点燃癫痫发作和MES癫痫发作的其他药物更有效。这些结果表明，一些H3拮抗剂可能是有用的抗癫痫药物，特别是继发性全身性癫痫发作和/或强直阵挛性癫痫发作在人类。
The effects of histamine H3 antagonists on amygdaloid kindled and maximal electroshock seizures in rats were studied to determine their potential as new antiepileptic drugs. Under pentobarbital anesthesia, rats were fixed to a stereotaxic apparatus and a stainless steel guide cannula for drug administration was implanted into the lateral ventricle. In amygdaloid kindled seizures, electrodes were implanted into the right amygdala and electroencephalogram was recorded bipolarly; stimulation was applied bipolarly every day by a constant current stimulator and continued until a generalized convulsion was obtained. In the maximal electroshock (MES) seizure test, electroconvulsion was induced by stimulating animals through ear-clip electrodes, and the durations of tonic and clonic seizures were measured. Thioperamide, clobenpropit, iodophenpropit, VUF5514, VUF5515 and VUF4929 caused a dose-dependent inhibition of both seizure stage and afterdischarge (AD) duration of amygdaloid kindled seizures. The duration of tonic seizure induced by MES was also inhibited by H3 antagonists, but the duration of clonic seizures were unchanged. Among the H3 antagonists tested, clobenpropit and iodophenpropit were somewhat more potent than the other drugs on amygdaloid kindled seizures and MES seizures, respectively. These results indicate that some H3 antagonists may be useful as antiepileptic drugs, especially for secondary generalized seizures and/or tonic-clonic seizures in humans.