新型Rho激酶抑制剂DL08052的一般药理学研究  

General pharmacology of the new Rho kinase inhibitor DL0805-2

作　　者：陈俞材 张惠芳[1] 林溢煌 王丹姝[1] 王蕊[1] 焦晓臻[1] 谢平[1] 方莲花[1] 杜冠华[1] 

机构地区：[1]中国医学科学院北京协和医学院药物研究所,药物靶点研究和新药筛选北京市重点实验室,北京100050

出　　处：《中国新药杂志》2015年第18期2065-2072,共8页Chinese Journal of New Drugs

基　　金：国家“重大新药创制”科技重大专项(2013ZX09103001-008,2012ZX09103101-078,2013ZX09508104)

摘　　要：目的:新结构Rho激酶抑制剂DL0805-2是前期发现的抗高血压急症候选药物,实验拟观察DL0805-2对心血管系统、呼吸系统和中枢神经系统的影响。方法:将SD大鼠30只随机分成DL0805-2低、中、高剂量组(3,10和30 mg·kg-1)、法舒地尔(fasudil)对照组和空白对照组,观察DL0805-2对大鼠心血管系统和呼吸系统的影响。将ICR种小鼠30只随机分组同前,按体表面积换算成相应剂量,观察DL0805-2对小鼠中枢神经系统的作用。结果:DL0805-2对心率、心电、心功能、呼吸频率和幅度、自主活动和爬杆能力无明显影响,对血压有一定的降低作用。结论:DL0805-2对中枢神经系统、呼吸系统和心功能均无明显影响,对血压有短暂的降低作用。DL0805-2不良反应较小,值得进一步研究和开发。Objective： To investigate the effects of DL0805-2 on cardiovascular, respiratory, and nervous systems. Methods： Thirty Sprague-Dawley rats were equally randomized into five groups： three groups of DL0805- 2 （3, 10, 30 rag- kg- 1 ） , fasudil group （ 10 rag. kg-~ ） and solvent control group. The effects of DL0805-2 on car- diovascular and respiratory systems were observed. Thirty ICR mice were equally randomized into five groups as a- bove. The dose was converted according to the body surface area, and the effects of DL0805-2 on central nervous systems were observed. Results： DL0805-2 had no significant effect on heart rate, ECG, heart function, respirato- ry frequency and amplitude, locomotor activity and ability of climbing pole, but could decrease blood pressure. Conclusion： DL0805-2 has no significant effect on the central nervous system, respiratory system and heart func- tion in spite of temporary decreasing the blood pressure. Therefore, the side effect of DL0805-2 is small; it is wor- thy of further research and development, and clinical application.

关 键 词：DL0805-2 一般药理学 RHO激酶抑制剂 法舒地尔 超声心动图 

分 类 号：R972[医药卫生—药品]