@article {YokoyamaP7.301作者= {Tomihisa Yokoyama Naohisa荒川和雪多芒Fumihiko松田和井上达Yutaka北野Makoto Takahashi和Naotoshi Yamamura和Kiyonori Kai}, title ={药理、药效和安全性配置文件的ds - 5565,一种新的α2δ配体(P7.301)},体积={82}={10}补充数量,elocation-id = {P7.301} ={2014},出版商= {Wolters Kluwer健康,公司代表美国神经病学学会},文摘={目的:澄清ds - 5565作为小说的特点α2δ配体,我们进行了实验使用普瑞巴林(调整)作为参考。首页背景:ds - 5565是一种镇痛药,结合α2δ亚基(α2δ-1和α2δ-2)压敏电阻器的Ca2 +渠道。α2δ-1是主要目标α2δ配体的镇痛效果。的贡献α2δ-2α2δ中枢神经系统副作用的配体仍有待阐明。设计/方法:亲和力、离解率研究和老鼠α2δ-1α2δ-2转染细胞。镇痛效果与冯·弗雷测试研究了链脲霉素(STZ)全身的糖尿病大鼠。中枢神经系统的副作用进行调查与rota-rod性能(RR)和运动活动(LA)的老鼠。血浆药物浓度测定质/ MS。结果:结合亲和力的ds - 5565α2δ-1和α2δ-2可比的调整。有趣的是ds - 5565显示比α2δ-2α2δ-1离解速率放缓,特别是α2δ-1而调整。ds - 5565显示强大的和持续的镇痛效果和ED50 ca 2.5毫克/公斤(ED50 forPGB: 29.3毫克/公斤)。 The plasma concentration of DS-5565 in the STZ rats was about 65-fold less than PGB. DS-5565 inhibited RR (ID50: 9.4 mg/kg) and LA (ID50: 43.9 mg/kg) and the ratios ID50/ED50 (CNS safety margin) were ca 3.8 in RR and ca 18 in LA. The ratios for PGB were 0.4 and 3.9, respectively. CONCLUSIONS: DS-5565 has superior analgesic effects with a wider CNS safety margin relative to PGB. These profiles of DS-5565 are possibly due to its unique binding characteristics to α2δ-1 and α2δ-2.Disclosure: Dr. Yokoyama has received personal compensation for activities with Daiichi Pharmaceutical Corp. as an employee. Dr. Arakawa has received personal compensation for activities with Daiichi Pharmaceutical Corporation as an employee. Dr. Domon has received personal compensation for activities with Daiichi Pharmaceutical Corp. as an employee. Dr. Matsuda has received personal compensation for activities with Daiichi Pharmaceutical Corp. Dr. Inoue has received personal compensation for activities with Daiichi Pharmaceutical Corp. as an employee. Dr. Kitano has received personal compensation for activities with Daiichi Pharmaceutical Corp. Dr. Takahashi has received personal compensation for activities with Daiichi Pharmaceutical Corp. as an employee. Dr. Yamamura has received personal compensation for activities with Daiichi Sankyo. Dr. has received personal compensation for activities with Daiichi Pharmaceutical Corp. as an employee.Thursday, May 1 2014, 3:00 pm-6:30 pm}, issn = {0028-3878}, URL = {//www.ez-admanager.com/content/82/10_Supplement/P7.301}, eprint = {//www.ez-admanager.com/content}, journal = {Neurology} }