Chemical Properties
White Crystalline Solid
Uses
vasodilator (cerebral), Ca antagonist
Uses
A potent calcium antagonist vasodilator which is considered to act by employing different mechanisms from the usual calcium channel blockers since it inhibits (1) calcium ionophore A23187 induced co
ntraction in arterial strips and (2) phenylephrine induced contraction in calcium free media suggesting that its site of action is in the intracellular space. Also reported to potently inhibit Rho-
associated Kinase (ROCK IC50= 10.7 uM).
Uses
Fasudil is a protein kinase A inhibitor and may be used in medicinal combinations for hepatitis treatment.
Definition
ChEBI: Fasudil is an isoquinoline substituted by a (1,4-diazepan-1-yl)sulfonyl group at position 5. It is a Rho-kinase inhibitor and its hydrochloride hydrate form is approved for the treatment of cerebral vasospasm and cerebral ischemia. It has a role as a geroprotector, an EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor, a vasodilator agent, a nootropic agent, a neuroprotective agent, an antihypertensive agent and a calcium channel blocker. It is a N-sulfonyldiazepane and a member of isoquinolines. It is a conjugate base of a fasudil(1+).
General Description
A cell-permeable, reversible, and ATP-competitive Ca
2+ antagonist with anti-vasospastic properties. Inhibits protein kinase A (K
i = 1.6 μM), protein kinase G (K
i = 1.6 μM), and myosin light chain kinase (K
i = 3.6 μM). Also reported to potently inhibit Rho-associated kinase (ROCK; IC
50 = 10.7 μM). Prevents apoptosis and enhances the survival and cloning efficiency of dissociated hES cells without affecting their pluripotency.
Biological Activity
Cyclic nucleotide-dependent protein kinase inhibitor and Rho-associated kinase inhibitor (IC50 = 10.7 μM). Ca2+ antagonist and vasodilator. Also inhibits proliferation of vascular smooth muscle cells.
Biochem/physiol Actions
Cell permeable: yes
in vitro
the inhibitory effects of fasudil on contractile responses to various agonists were examined on strips of rabbit aorta. the concentration-response curves to 5-hydroxytryptamine, prostaglandin f2alpha, histamine, angiotensin ii, noradrenaline and dopamine were concentration-dependently shifted to the right in the presence of fasudil [1].
in vivo
intra-coronary administration of fasudil to dog dose-dependently increased coronary blood flow, with no effect on mean blood pressure or heart rate. intra-coronary infusion of atropine, diphenhydramine or propranolol did not modify the in vivo coronary vasodilator response to fasudil [1].
References
[1] asano t, suzuki t, tsuchiya m, satoh s, ikegaki i, shibuya m, suzuki y, hidaka h. vasodilator actions of ha1077 in vitro and in vivo putatively mediated by the inhibition of protein kinase. br j pharmacol. 1989 dec;98(4):1091-100.
[2] zhao j, zhou d, guo j, ren z, zhou l, wang s, zhang y, xu b, zhao k, wang r, mao y, xu b, zhang x; fasudil aneurysmal subarachnoid hemorrhage study group. efficacy and safety of fasudil in patients with subarachnoid hemorrhage: final results of a randomized trial of fasudil versus nimodipine. neurol med chir (tokyo). 2011;51(10):679-83.
