Fasudil HCl

Fasudil is a class of calcium antagonists. Fasudil produces a competitive inhibition of the Ca²⁺-induced contraction of the depolarized rabbit aorta. Fasudil is able to inhibit contractile responses to KCl, phenylephnne (PHE) and prostaglandin (PG) F2a. ^[2]

Fasudil also exhibits vasodilator actions by inhibition of 5-hydroxytryptamine, noradrenaline, histamine, angiotensin, and dopamine induced spiral strips contraction. ^[3]

Fasudil induces disorganization of actin stress fiber and cell migration inhibition. ^[4]

Fasudil inhibits hepatic stellate cells spreading, the formation of stress fibers, and expression of α-SMA with concomitant suppression of cell growth, but does not induce apoptosis. Fasudil suppresses the LPA-induced phosphorylation of ERK1/2, JNK and p38 MAPK. ^[5]

Intra-coronary injection of Fasudil to dogs (30 μg i.a.) produces an approximate 50% increase in CBF. Fasudil (0.01, 0.03, 0.1 and 0.3 mg/kg, bolus, i.v.) dose-dependently decreases MBP and increases HR, VBF, CBF, RBF, and FBF. A total dose of 1.0 ng/mL Fasudil increases cardiac output. The infusion of Fasudil i.v. produces a significant fall in MBP, left ventricular systolic pressure and total peripheral resistance with an increase in HR and cardiac output, but without significant changes in right atrial pressure, dP/dt or left ventricular minute work in dogs. ^[3]

Fasudil administration displays protectable effects on cardiovascular disease and reduces the activation of JNK and attenuates mitochondrial-nuclear translocation of AIF under ischemic injury. ^[6]

The oral administration of Fasudil (a dosage of 100 mg/kg/day) significantly reduces incidence and mean maximum clinical score of EAE in SJL/J mice immunized with PLP p139-151. Treatment of mice with Fasudil suppresses the proliferative response of splenocytes to the antigen. Oral administration of Fasudil decreases inflammation, demyelination, axonal loss and APP positivein spinal cord of Fasudil-treated mice. ^[7]

• Cyclic AMP-dependent protein kinase activity assay

  Cyclic AMP-dependent protein kinase activity is assayed in a reaction mixture containing, in a final volume of 0.2 mL, 50 mM Tris-HCl (pH 7.0), 10 mM magnesium acetate, 2 mM EGTA, 1 μM cyclic AMP or absence of cyclic AMP, 3.3 to 20 μM [r-³²P] ATP (4×10⁵ c.p.m.), 0.5 μg of the enzyme, 100 μg of histone H₂B and compound. The mixture is incubated at 30 ℃ for 5 min. The reaction is terminated by adding 1mL of ice-cold 20% trichloroacetic acid after adding 500 μg of bovine serum albumin as a carrier protein. The sample is centrifuged at 3000 r.p.m. for 15min, the pellet is resuspended in ice-cold 10% trichloro-acetic acid solution and the centrifugation-resuspension cycle is repeated three times. The final pellet is dissolved in 1 mL of 1 N NaOH and radioactivity is measured with a liquid scintillation counter.

• Animal Models

  Mongrel dogs

• Dosages

  0.01, 0.03, 0.1 and 0.3 mg/kg

• Administration

  i.v.