法舒地尔于1995年作为治疗蛛网膜下腔出血药物在日本上市,当时对它的定义是新型钙离子拮抗剂,直到Rho激酶(Rho associated kinase,ROCK)被发现后,它的作用机制才真正被阐明.它主要通过抑制ROCK起到强效扩张血管,保护缺血心脑组织的作用.近年来,越来越多的报道指出法舒地尔具有神经保护作用,它对中枢神经系统疾病如脊髓损伤、阿尔茨海默病、多发性硬化症、神经性疼痛等都有着显著的疗效.为提高法舒地尔对ROCK的选择性,对它的结构进行改造,得到一系列类似物,其中一些还显示出比法舒地尔更强的活性和更高的选择性.本文就法舒地尔其类似物对神经系统疾病潜在的治疗作用及联合用药进行了综述.%Fasudil, which is initially defined as a novel calcium antagonist, has been clinically applied since 1995 for the treatment of cerebral vasospasm after hemorrhage in the subarachnoid space in Japan. The mechanism of action has not been clarified until Rho kinase (ROCK) was found. This drug exerts strong vasodilative effect through inhibiting ROCK. Recently, increasing evidence indicates that fasudil as a neuroprotective agent can markedly exert therapeutic effect on central nervous system disorders, such as spinal cord injury, Alzheimer disease and multiple sclerosis, and so on. To improve the selectivity of fasudil to ROCK, a number of analogs have been synthesized based on its structure, and proved to be more potent or more selective than fasudil. Herein, the potential of fasudil in the treatment for central nervous system disorders and the study of its analogs were summarized. Moreover, the combination strategies of fasudil were also discussed.
展开▼
