Development of a new antiepileptic agent without hypnotic effects

开发一种无催眠作用的新型抗癫痫药

• 批准号: 11557059
• 负责人: IINUMA Kazuie
• 金额: $ 0.77万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11557059/
• 关键词: PTZ kindling; methylhistamine; H3-receptor; H1受容体ノックアウトマウス

Epilepsy model was developed in ICR mice according to daily intraperitoneal(ip)injection of pentylentetrazol(PTZ). The daily ip administration of 40mg of PTZ induced generalized convulsion about 25 days after the initial injection. The phenomenon of kindling formation showed dose dependency of PTZ.Histamine H3-receptors control the release of histamine from the histaminegic neurons in the central nervous system. The H3-receptor inhibits the histamine release.Daily ip administration of methylhistamine, an agonist of H3-receptor induced an acceleration of PTZ kindling. The strage 5 convulsion was developed in 100%. mice 8 days after the PTZ administration. The duration of seizures was prolonged and the latency after injection was shortened in mice administered 10mg of methylhistamine than those with 5mg of methylhistamine. These results imply that convulsive seizures were accelerated through H3-receptors probably due to inhibition of histamine release. We speulate that histamine H3-receptor antagonist may inhibit the development the PTZ kindling. This experiment is the next project.

ICR小鼠每日腹腔注射戊四氮（PTZ）建立癫痫模型。首次注射后约25天，每天ip给予40 mg PTZ诱导全身惊厥。组胺H_3受体控制中枢组胺能神经元释放组胺。H_3受体抑制组胺释放，每天ip H_3受体激动剂甲基组胺可加速戊四氮点燃。5级惊厥发生率100%。PTZ给药后8天的小鼠。甲基组胺10mg组小鼠惊厥持续时间较5mg组延长，注射后潜伏期较5mg组缩短。这些结果表明，惊厥发作加速通过H3受体可能是由于抑制组胺释放。提示组胺H_3受体拮抗剂可抑制戊四氮点燃的发展。这个实验是下一个项目。

项目成果

飯沼一宇: "中枢ヒスタミンと痙攣"別冊・医学のあゆみ「ヒスタミン研究の最近の進歩」. 94-96 (2000)

Kazuu Iinuma：“中枢组胺和惊厥”单独卷：医学史“组胺研究的最新进展”94-96（2000）。

Kazuie Iinuma: "Central histaminergic neuron system and convulsion"Journal of Clinical and Experimental Medicine. 94-96 (2000)

Kazuie Iinuma：《中枢组胺能神经元系统与惊厥》临床与实验医学杂志。