Description
Fasudil hydrochloride, a novel calcium antagonistic vasodilator, was marketed
for the treatment of cerebral vasospasm following subarachnoid hemorrhage
(SAH). Fasudil is also a potent inhibitor of myosin light chain kinase and protein kinase
C. In contrast to other calcium channel blockers, which regulate the influx of calcium
ions through the cell membrane but not involved in the intracellular regulatory
mechanism of the calcium, fasudil was suggested to have an intracellular mode of
action in relaxing vascular smooth muscle. In patients with neurological deficits due to
vasospasm, fasudil decreased the occurrence of angiographic severe and
symptomatic vasospasm and cerebral infarction without decreasing systemic blood
pressure. Fasudil is reportedly in clinical trials for acute ischemic stroke, sequelae of
cerebral vascular diseases and angina pectoris.
Originator
Asahi Chemical (Japan)
Application
Fasudil hydrochloride (HA-1077) is a prodrug of hydroxyfasudil [H1745 (HCl salt)], which is a potent and selective Rho kinase (a protein phosphatase) inhibitor. Hydroxyfasudil inhibits phosphorylation of myosin light chain, the final step in the vascular smooth muscle contractile mechanism, by inhibiting Rho kinase. Fasudil has been used as a vasodilator for the treatment of cerebral vasospasm. (The product is for research purpose only.)
Uses
vasodilator, potent Rho-kinase inhibitor
Definition
ChEBI: Fasudil hydrochloride is a hydrochloride obtained by reaction of fasudil with one equivalent of hydrochloric acid. It has a role as an antihypertensive agent, a calcium channel blocker, an EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor, a neuroprotective agent, a nootropic agent and a vasodilator agent. It contains a fasudil(1+).
Biological Activity
Fasudil hydrochloride is a cyclic nucleotide-dependent protein kinase inhibitor and Rho-associated kinase inhibitor (IC50 = 10.7 μM). Fasudil suppresses MMP-2 expression and induces apoptosis in glioblastoma cells in vivo. Fasudil is a Ca2+ antagonist, vasodilator and inhibits proliferation of vascular smooth muscle cells. Fasudil binds to α-synuclein to reduce aggregate formation in cellular models of Parkinson's disease, also displays neuroprotective properties and increases survival of dopaminergic neurons in vivo.
References
1) Davies et al. (2000), Specificity and mechanism of action of some commonly used protein kinase inhibitors; Biochem. J., 351 95
2) Anwar et al. (2013), Signal transduction and modulating pathways in tryptamine-evoked vasopressor responses of the rat isolated perfused mesenteric bed; Vascul. Pharmacol., 58 140
3) Jiang et al. (2012), Fasudil, a rho-kinase inhibitor, attenuates bleomycin-induced pulmonary fibrosis in mice; Int. J. Mol. Sci., 13 8293
