Development of a new antiepileptic agent without hypnotic effects

Research Project

Project/Area Number	11557059
Research Category	Grant-in-Aid for Scientific Research (B).
Allocation Type	Single-year Grants
Section	展開研究
Research Field	Pediatrics
Research Institution	Tohoku University
Principal Investigator	IINUMA Kazuie Tohoku University, Department of Pediatrics Professor, 大学院・医学系研究科, 教授 (80004927)
Co-Investigator(Kenkyū-buntansha)	MASUDA Yoshinobu Dainippon Pharmaceutical Co.Chief Researcher, 創薬研究所, 主任研究員 YOKOYAMA Hiroyuki Tohoku University, Department of Pediatrics Research Associate, 医学部・附属病院, 助手 (40271952) HAGINOYA Kazuhiro Tohoku University, Department of Pediatrics Lecturer, 大学院・医学系研究科, 講師 (00208414)
Project Period (FY)	1999 – 2000
Project Status	Completed (Fiscal Year 2000)
Budget Amount *help	¥1,200,000 (Direct Cost: ¥1,200,000) Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywords	PTZ kindling / methylhistamine / H3-receptor / H1受容体ノックアウトマウス
Research Abstract	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.