TY - T1的药理、药效和安全性配置文件的ds - 5565,一种新型α<子> < /订阅>δ2配体(P7.301) JF -神经学乔-神经学六世- 82 - 10补充SP - P7.301盟Tomihisa Yokoyama盟Naohisa荒川A首页U -雪多芒盟Fumihiko松田Yutaka北野AU -井上达盟盟- Makoto Takahashi盟Naotoshi Yamamura AU - Kiyonori Kai Y1 - 2014/04/08 UR - //www.ez-admanager.com/content/82/10_Supplement/P7.301.abstract N2 -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。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 ER -