Pleiotropic effects of the rho-kinase inhibitor fasudil after subarachnoid hemorrhage: a review of preclinical and clinical studies

• Published in: Current vascular pharmacology Vol. 12; no. 5; p. 758
• Main Authors: Satoh, Shin-ichi, Ikegaki, Ichiro, Kawasaki, Koh, Asano, Toshio, Shibuya, Masato
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.01.2014
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - therapeutic use; Animals; Brain Ischemia - drug therapy; Brain Ischemia - enzymology; Clinical Trials as Topic - methods; Drug Evaluation, Preclinical - methods; Genetic Pleiotropy - drug effects; Genetic Pleiotropy - physiology; Humans; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - enzymology; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; rho-Associated Kinases - antagonists & inhibitors; rho-Associated Kinases - metabolism; Subarachnoid Hemorrhage - drug therapy; Subarachnoid Hemorrhage - enzymology; Treatment Outcome
• ISSN: 1875-6212
• DOI: 10.2174/1570161112666140613115813

There is growing evidence that Rho-kinase contributes to cardiovascular disease, which has made Rho-kinase a target for the treatment of human diseases. To date, the only Rho-kinase inhibitor employed clinically in humans is fasudil, which has been used for the prevention of cerebral vasospasm and subsequent ischemic injury after surgery for subarachnoid hemorrhage (SAH). A number of pathological processes, in particular hemodynamic dysfunctions and inflammatory reactions, are thought to be related in the pathogenesis of delayed cerebral vasospasm and subsequent ischemic injury after SAH. This review focuses on fasudil's pleiotropic therapeutic effects: amelioration of hemodynamic dysfunction and inflammation, and discusses in detail the clinical studies on fasudil administered after the occurrence of SAH.