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Systematic (IUPAC) name
Clinical data
AHFS/Drugs.com International Drug Names
Pharmacokinetic data
Bioavailability well absorbed
Metabolism metabolized quickly to hydroxyfasudil
Biological half-life 0.76 hours. Active metabolite (hydroxyfasudil) 4.66 hours.
CAS Number 103745-39-7 YesY
ATC code C04AX32
PubChem CID: 3547
KEGG D07941 YesY
Chemical data
Formula C14H17N3O2S
Molecular mass 291.36 g/mol
 YesY (what is this?)  (verify)

Fasudil hydrochloride (INN) is a potent Rho-kinase inhibitor and vasodilator.[1] Since it was discovered, it has been used for the treatment of cerebral vasospasm, which is often due to subarachnoid hemorrhage,[2] as well as to improve the cognitive decline seen in stroke victims. It has been found to be effective for the treatment of pulmonary hypertension.[3] It was demonstrated in February 2009 that fasudil could also be used to enhance memory and improve the prognosis of Alzheimers patients.[4]

It is approved for use in Japan and China, but has not been approved by the United States Food and Drug Administration or by the European Medicines Agency.

Molecular mechanism[edit]

Fasudil (HA-1077) is a selective RhoA/Rho kinase (ROCK) inhibitor.[5] ROCK is an enzyme that plays an important role in mediating vasoconstriction and vascular remodeling in the pathogenesis of PH. ROCK induces vasoconstriction by phosphorylating the myosin-binding subunit of myosin light chain (MLC) phosphatase, thus decreasing MLC phosphatase activity and enhancing vascular smooth muscle contraction.[5]

ACE expression[edit]

Angiotensin-converting enzyme (ACE) is an enzyme that catalyzes the conversion of angiotensin-I (Ang-I) to angiotensin-II (Ang-II). Ang-II is a peptide hormone which increases blood pressure by initiating vasoconstriction and aldosterone secretion. ROCK increases ACE expression and activity in PH. By inhibiting ROCK with fasudil, circulating ACE and Ang-II are reduced, leading to a decrease in pulmonary vascular pressure.[6]

eNOS expression[edit]

Endothelial nitric oxide synthase (eNOS) mediates the production of the vasodilator nitric oxide (NO). Pulmonary arterial cell cultures treated with fasudil showed a significant increase in eNOS mRNA levels in a dose dependent manner, and the half-life of eNOS mRNA increased 2-folds. These findings suggested that ROCK inhibition with fasudil increases eNOS expression by stabilizing eNOS mRNA, which contributed to an increase of NO level to enhance vasodilation.[7]

ERK activation[edit]

The proliferative effects of ROCK on vascular endothelial cells is due to the activation of extracellular signal-regulated kinase (ERK).[8] ERK mediates cell proliferation via the phosphorylation of p27Kip1, thus accelerating the degradation rate of p27Kip1.[9] p27Kip1 is a cyclin-dependent kinase (CDK) inhibitor which down-regulates cell cycle by binding cyclin-CDK complex.[10] Human pulmonary arterial smooth muscle cells treated with fasudil showed a decrease in cell proliferation in a dose-dependent manner. Fasudil also decreases ERK activities, as well as increases level of p27Kip1. This suggested that the anti-proliferative effects of fasudil is due to the decrease of ERK activities via the inhibition of ROCK.[8]

See also[edit]

  • Ripasudil, a fasudil derivative used to treat glaucoma and ocular hypertension


  1. ^ "Drug Found That Could Reduce Risk Of Alzheimer's". Science Daily. 
  2. ^ Shibuya M, Suzuki Y (Sep 1993). "[Treatment of cerebral vasospasm by a protein kinase inhibitor AT 877]". Nō to Shinkei = Brain and Nerve (in Japanese) 45 (9): 819–24. PMID 8217408. 
  3. ^ Doggrell SA (Sep 2005). "Rho-kinase inhibitors show promise in pulmonary hypertension". Expert Opinion on Investigational Drugs 14 (9): 1157–9. doi:10.1517/13543784.14.9.1157. PMID 16144499. 
  4. ^ Huentelman MJ, Stephan DA, Talboom J, Corneveaux JJ, Reiman DM, Gerber JD, Barnes CA, Alexander GE, Reiman EM, Bimonte-Nelson HA (Feb 2009). "Peripheral delivery of a ROCK inhibitor improves learning and working memory". Behavioral Neuroscience 123 (1): 218–23. doi:10.1037/a0014260. PMC 2701389. PMID 19170447. 
  5. ^ a b Nagumo H, Sasaki Y, Ono Y, Okamoto H, Seto M, Takuwa Y (Jan 2000). "Rho kinase inhibitor HA-1077 prevents Rho-mediated myosin phosphatase inhibition in smooth muscle cells". American Journal of Physiology. Cell Physiology 278 (1): C57–65. PMID 10644512. 
  6. ^ Ocaranza MP, Rivera P, Novoa U, Pinto M, González L, Chiong M, Lavandero S, Jalil JE (Apr 2011). "Rho kinase inhibition activates the homologous angiotensin-converting enzyme-angiotensin-(1-9) axis in experimental hypertension". Journal of Hypertension 29 (4): 706–15. doi:10.1097/HJH.0b013e3283440665. PMID 21330937. 
  7. ^ Takemoto M, Sun J, Hiroki J, Shimokawa H, Liao JK (Jul 2002). "Rho-kinase mediates hypoxia-induced downregulation of endothelial nitric oxide synthase". Circulation 106 (1): 57–62. PMID 12093770. 
  8. ^ a b Liu AJ, Ling F, Wang D, Wang Q, Lü XD, Liu YL (Oct 2011). "Fasudil inhibits platelet-derived growth factor-induced human pulmonary artery smooth muscle cell proliferation by up-regulation of p27kip¹ via the ERK signal pathway". Chinese Medical Journal 124 (19): 3098–104. PMID 22040563. 
  9. ^ Delmas C, Manenti S, Boudjelal A, Peyssonnaux C, Eychène A, Darbon JM (Sep 2001). "The p42/p44 mitogen-activated protein kinase activation triggers p27Kip1 degradation independently of CDK2/cyclin E in NIH 3T3 cells". The Journal of Biological Chemistry 276 (37): 34958–65. doi:10.1074/jbc.m101714200. PMID 11418594. 
  10. ^ Fouty BW, Rodman DM (Mar 2003). "Mevastatin can cause G1 arrest and induce apoptosis in pulmonary artery smooth muscle cells through a p27Kip1-independent pathway". Circulation Research 92 (5): 501–9. doi:10.1161/01.RES.0000061180.03813.0F. PMID 12600884.