Mechanism responsible for epileptogenic activity by first-generation H1-antagonists in rats
Mechanism responsible for epileptogenic activity by first-generation H1-antagonists in rats
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DOI：
10.1016/s0006-8993(00)03041-9
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发表时间：
2000-12-22
期刊：
影响因子：
2.9
通讯作者：
Okuma, C
中科院分区：
文献类型：
--
作者：
Kamei, C;Ohuchi, M;Okuma, C
在目前的研究中，我们已经证明了多种第一代h1拮抗剂引起大鼠的行为和脑电图癫痫发作。吡咯胺的致痫性比氯苯那敏或苯海拉明更强。相比之下，第二代h1拮抗剂氯雷他定和依巴斯汀没有诱导可检测到的致痫活性。腹腔注射组氨酸可抑制吡拉胺、苯海拉明和氯苯那敏诱发的脑电图发作；然而，未观察到肉毒杆菌碱的拮抗作用。这些结果清楚地表明，第一代h1拮抗剂的致痫活性依赖于中枢作用的组胺能机制。(C) 2000 Elsevier Science B.V.版权所有
In the present study, we have demonstrated that multiple first-generation H1-antagonists caused behavioral and EEG seizures in rats. The epileptogenic property of pyrilamine was more potent than either chlorpheniramine or diphenhydramine. In contrast, the second-generation H1-antagonists, loratadine and ebastine did not induce detectable epileptogenic activity. Intraperitoneal injection of histidine inhibited the EEG seizures induced by pyrilamine, diphenhydramine or chlorpheniramine; however no antagonism was observed with physostigmine. These results clearly suggest that the epileptogenic activity of first-generation H1-antagonists is dependent upon a centrally acting histaminergic mechanism. (C) 2000 Elsevier Science B.V. All rights reserved.