Overview
Fasudil (HA-1077) is a small-molecule isoquinoline sulfonamide inhibitor of Rho-associated coiled-coil kinase (ROCK), the principal downstream effector of the small GTPase RhoA. It was developed by Asahi Kasei and approved in Japan in 1995 for the prevention and treatment of cerebral vasospasm following subarachnoid hemorrhage; it is also approved in China for similar indications. Fasudil is not FDA-approved in the United States.
ROCK signaling regulates cytoskeletal dynamics, smooth-muscle contraction, endothelial function, neuronal morphology, and immune cell migration. By inhibiting ROCK1 and ROCK2, fasudil produces vasodilation (particularly cerebral), reduces vascular smooth-muscle hyperreactivity, attenuates inflammatory cell trafficking, and promotes neurite outgrowth and axonal regeneration in preclinical models.
Beyond cerebral vasospasm, fasudil and related ROCK inhibitors have been studied in pulmonary arterial hypertension, stable angina, Raynaud's phenomenon, glaucoma, multiple sclerosis, amyotrophic lateral sclerosis (ALS), Alzheimer's disease, and spinal cord injury. ROCK inhibition has also drawn interest from longevity researchers because of its overlap with senescence and inflammation pathways, although direct lifespan data in mammals are limited.
Fasudil is generally well tolerated in its approved indication. Off-label use—particularly oral preparations sourced as research chemicals—is increasing in nootropic and longevity communities, but pharmacokinetics and safety of chronic oral dosing in healthy individuals have not been adequately characterized.
Quick facts
- Mechanism
- Rho-kinase (ROCK1/2) inhibitor with vasodilatory, anti-inflammatory, and neuroregenerative effects
- Primary use
- Cerebral vasospasm prevention; neuroprotection and longevity research
- Evidence
- moderate
- FDA
- Not approved
- Route
- Intravenous (approved) or oral (research / off-label in some regions)
- Typical results
- Reduces cerebral vasospasm-related ischemic events after subarachnoid hemorrhage; modulates vascular and CNS endpoints in early trials
Chemical information
Fasudil (C₁₄H₁₇N₃O₂S) is a longevity compound with a molecular weight of 291.37 g/mol. Its structural characteristics underpin its biological activity in longevity and anti-aging research.
How Fasudil works
Fasudil and its active metabolite hydroxyfasudil reversibly inhibit ROCK1 and ROCK2 by competing with ATP at their kinase domains. ROCK inhibition dephosphorylates myosin light chain in vascular smooth muscle (producing vasodilation), modulates actin cytoskeletal dynamics in neurons (promoting axonal sprouting), and reduces leukocyte adhesion-molecule expression and migration. Downstream effects include lowered vascular tone, enhanced endothelial nitric oxide signaling, and suppression of NF-κB-driven inflammation.
In cerebral vasospasm following subarachnoid hemorrhage, sustained vascular smooth-muscle contraction in cerebral arteries causes delayed ischemic deficits. Fasudil reverses this hypercontractile state, improves cerebral perfusion, and reduces symptomatic vasospasm and infarction in randomized trials.
In the central nervous system, ROCK inhibition antagonizes growth-cone collapse induced by myelin-associated inhibitors (Nogo-A, MAG, OMgp) and chondroitin sulfate proteoglycans, enabling axonal regeneration. Preclinical models of spinal cord injury, stroke, ALS, and Alzheimer's all show improved structural and functional outcomes with fasudil.
In endothelial cells, ROCK inhibition increases eNOS expression and stability, enhances NO bioavailability, and improves flow-mediated dilation—mechanisms that may explain benefits in pulmonary hypertension and atherosclerosis. ROCK signaling is also implicated in cellular senescence and SASP (senescence-associated secretory phenotype), providing a rationale for longevity exploration.
- ROCK1/2 inhibition: Competitive ATP-site inhibitor of Rho-kinase
- Vasodilation: Dephosphorylates myosin light chain in vascular smooth muscle
- Axonal regeneration: Reverses growth-cone collapse driven by myelin inhibitors
- Endothelial protection: Increases eNOS expression and NO bioavailability
- Anti-inflammatory: Reduces leukocyte adhesion and NF-κB activation
Pharmacokinetics
| Parameter | Value | Significance |
|---|---|---|
| Molecular Mass | 291.37 g/mol | Small isoquinoline sulfonamide |
| IV half-life | ~30–50 minutes (parent); ~7–8 hours (hydroxyfasudil) | Active metabolite extends pharmacodynamic effect |
| Oral bioavailability | Low (~25–35%, based on limited data) | Approved formulation is IV; oral dosing is research-only |
| Metabolism | Hepatic, primarily to hydroxyfasudil (active) | Hydroxyfasudil contributes substantially to clinical effect |
| Elimination | Renal and biliary | Caution in hepatic or renal impairment |
Dosing & administration
Fasudil dosing varies by indication and individual factors. No FDA-approved dosing exists for this compound; protocols in the literature derive from limited clinical or preclinical data and practitioner experience.
Any use should be conducted under qualified medical supervision with appropriate monitoring of safety markers.
Important: These dosing ranges are not FDA-approved. Any use should be under qualified medical supervision.
Side effects & safety
Safety data for Fasudil is primarily derived from preclinical studies and limited human data. Long-term effects in humans remain incompletely characterized.
Common
- • Headache
- • Facial flushing and warmth
- • Hypotension and dizziness
- • Mild hepatic enzyme elevation
- • Nausea
Serious / potential risks
- • Symptomatic hypotension
- • Intracranial hemorrhage in vulnerable patients
- • Bradycardia and conduction disturbances (rare)
- • Hepatic injury (rare; monitor LFTs with prolonged use)
- • Unknown long-term safety of chronic oral use
Drug interactions
| Medication | Interaction | Recommendation |
|---|---|---|
| Antihypertensives | Additive blood-pressure lowering | Monitor for hypotension at initiation |
| Anticoagulants/antiplatelets | Theoretical additive bleeding risk | Monitor closely in post-SAH or perioperative settings |
| Other vasodilators (nitrates, PDE5 inhibitors) | Additive vasodilation and hypotension | Use with caution |
| CYP-modulating drugs | Limited data on hepatic metabolism interactions | Pharmacovigilance with chronic dosing |
Storage & handling
Lyophilized (powder)
- • Store at -20°C to 4°C (freezer or refrigerator)
- • Protect from light and moisture
- • Stable for 12–24 months when stored properly
- • Keep in original sealed container until reconstitution
Reconstituted solution
- • Refrigerate at 2–8°C after reconstitution
- • Use bacteriostatic water for multi-dose reconstitution
- • Typical stability: 14–28 days refrigerated
- • Do not freeze reconstituted solution
Cost & availability
| Source | Cost | Notes |
|---|---|---|
| Research suppliers | Varies widely | Quality and purity vary significantly between sources |
| Compounding pharmacies | Prescription required | Higher quality assurance and purity testing |
The bottom line
Fasudil is a longevity compound with research interest in rock inhibition, cerebral vasospasm, neuroprotection. While preclinical evidence is encouraging, it remains investigational and is not FDA-approved. Any use should be under qualified medical supervision.
Best for
- • Researchers studying longevity and anti-aging research
- • Individuals interested in rock inhibition under medical guidance
Not for
- • Self-administration without medical supervision
- • Pregnant or breastfeeding individuals
- • Individuals with contraindicated conditions
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Frequently asked questions
References
- [1] Shibuya M, Suzuki Y, Sugita K, et al.. Effect of AT877 on cerebral vasospasm after aneurysmal subarachnoid hemorrhage. J Neurosurg (1992). doi: 10.3171/jns.1992.76.4.0571 PMID: 1545245
- [2] Olson MF.. Applications for ROCK kinase inhibition. Curr Opin Cell Biol (2008). doi: 10.1016/j.ceb.2008.01.005 PMID: 18282695
- [3] Tönges L, Frank T, Tatenhorst L, et al.. Inhibition of rho kinase enhances survival of dopaminergic neurons and attenuates axonal loss in a mouse model of Parkinson's disease. Brain (2012). doi: 10.1093/brain/aws254 PMID: 23065793
- [4] Koch JC, Tatenhorst L, Roser AE, et al.. ROCK inhibition in models of neurodegeneration and its potential for clinical translation. Pharmacol Ther (2018). doi: 10.1016/j.pharmthera.2018.03.008 PMID: 29621594