Development of a new antiepileptic agent without hypnotic effects

通过每日腹腔注射戊四氮唑（PTZ）建立ICR小鼠癫痫模型。首次注射后约25天，每日注射40mg PTZ可引起全身惊厥。PTZ的引燃形成表现出剂量依赖性。组胺h3受体控制中枢神经系统中组胺神经元的组胺释放。h3受体抑制组胺的释放。每日给予甲基组胺（h3受体激动剂）可加速PTZ点燃。奇怪的抽搐是100%发生的。PTZ给药后8天。与5mg组相比，10mg组小鼠癫痫发作持续时间延长，注射后潜伏期缩短。这些结果表明，h3受体可能由于抑制组胺释放而加速惊厥发作。我们推测组胺h3受体拮抗剂可能抑制PTZ点燃的发生。这个实验是下一个项目。

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.