| Identification | Back Directory | [Name]
Levosimendan | [CAS]
141505-33-1 | [Synonyms]
Simda
Simdax
OR-1259
LEVOSIMENDAN
(R)-Simendan
LevosimendanC14H12N60
(R)-2-[[4-(1,4,5,6-TETRAHYDRO-4-METHYL-6-OXO-3-PYRIDAZINYL)PHENYL] HYDROZONO]PRO
-2-[[4-(1，4，5，6-Tetrahydro-4-methyl-6-oxo-3-pyridazinyl)19henyl]hydrazono]Propandinitrile
R)-((4-(1,4,5,6-Tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl)hydrazono) propanedintrile
[[4-[(4R)-1,4,5,6-Terahydro-4-methyl-6-oxo-3-pyridazinyl]phenyl]hydrazono]propanedinitrile
(R)-2-(2-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)hydrazono)malononitrile
Mesoxalonitrile (-)-{p-[(R)-1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl]phenyl}hydrazone
Propanedinitrile, [[4-[(4R)-1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl]phenyl]hydrazono]-
2-[2-[4-[(4R)-1,4,5,6-Tetrahydro-4-methyl-6-oxo-3-pyridazinyl]phenyl]hydrazinylidene]-propanedinitrile
Propanedinitrile,2-[2-[4-[(4R)-1,4,5,6-tetrahydro-4-Methyl-6-oxo-3-pyridazinyl]phenyl]hydrazinylidene]- | [EINECS(EC#)]
663-528-6 | [Molecular Formula]
C14H12N6O | [MDL Number]
MFCD00867135 | [MOL File]
141505-33-1.mol | [Molecular Weight]
280.28 |
| Chemical Properties | Back Directory | [Appearance]
Yellow Crystalline Powder | [Melting point ]
216-219°C (dec.) | [alpha ]
D25 -566° (tetrahydrofurane/methanol) | [density ]
1.33±0.1 g/cm3(Predicted) | [storage temp. ]
-20°C Freezer | [solubility ]
DMSO: ≥20mg/mL | [form ]
powder | [pka]
6.3(at 25℃) | [color ]
yellow | [optical activity]
[α]/D -500 to -650°, c = 0.5 in THF |
| Hazard Information | Back Directory | [Chemical Properties]
Yellow Crystalline Powder | [Usage]
anesthetic | [Usage]
Bioactive enantiomer of racemate, Simendan. Positive inotropic agent with vasodilating activity. Cardiotonic | [Description]
Levosimendan was introduced in Sweden as an i.v. infusion for the treatment of acute
heart failure or refractory symptoms of chronic heart failure in cases where conventional
treatment (e.g., diuretic or ACE inhibitor) is not sufficient. Levosimendan is the (R)-
enantiomer of simendan that belongs to the same class as pimobendan (Boehringer
Ingelheim). Levosimendan is an innovative myofilament calcium sensitizer that increases
myocardial contractility by selectively binding to the N-terminus of troponin C and by
stabilizing the Ca2+-bound conformation of this contractile protein. It also activates
ventricular and arterial adenostne triphosphate-regulated potassium channels which
causes vasodilatation in vascular smooth muscle and protects myocardium against
infarction. Its low phosphodiesterase III inhibiting activity is probably not responsible for its
positive inotropic, lusitropic and dilating effects. Unlike other cardiotonic drugs,
levosimendan is able to produce positive inotropic effects without prolonging myocardial
relaxation or increasing the incidence of malignant arrythmias. It was clinically shown to
have a lower risk of mortality in patients with heart failure when compared to placebo and
dobutamine. Since it has a larger potential, levosimendan is currently under further clinical
evaluation as a chronic treatment for congestive heart failure. | [Originator]
Orion (Finland) | [Uses]
anesthetic | [Uses]
Bioactive enantiomer of racemate, Simendan. Positive inotropic agent with vasodilating activity. Cardiotonic | [Definition]
ChEBI: Levosimendan is a hydrazone, a pyridazinone and a nitrile. It has a role as a vasodilator agent, an EC 3.1.4.17 (3',5'-cyclic-nucleotide phosphodiesterase) inhibitor, a cardiotonic drug and an anti-arrhythmia drug. | [Brand name]
Simdax (Orion Pharmaceutica,
Finland). | [General Description]
Levosimendan is a calcium sensitizer that can cause increased cardiac contractility by binding troponin C (EC50 = 9 nM), promotes vasodilation by activating ATP-sensitive potassium channels on vascular smooth muscle cells (EC50 = 0.28 μM), and performs a cardioprotective function by prompting the opening of mitochondrial potassium channels in cardiomyocytes. It also has been reported to inhibit phosphodiesterases 3 and 4 in left ventricular cardiac tissue with IC50 values of 2.5 nM and 25 μM, respectively. | [Biochem/physiol Actions]
Levosimendan has a potential to inhibit both acute human immunodeficiency virus type 1 (HIV-1) replication and the reactivation of latent HIV-1 proviruses. Therefore, it is considered to be a promising anti-HIV-1 agent. | [Clinical Use]
Levosimendan is the bioactive enantiomer of racemate of Simendan. It acts as a positive inotropic agent with vasodilating activity. Levosimendan functions as a cardiotonic agent, promoting cardiac function and increasing blood vessel dilation. Levosimendan has been used for screening its anti-human immunodeficiency virus type 1 (HIV-1) property. It has also been used for screening its cytotoxic effects in TP53 mutant and wild-type lung adenocarcinoma cell lines. | [Mode of action]
Levosimendan is an innovative myofilament calcium sensitizer that increases myocardial contractility by selectively binding to the N-terminus of troponin C and by stabilizing the Ca2+-bound conformation of this contractile protein. It also activates ventricular and arterial adenostne triphosphate-regulated potassium channels which causes vasodilatation in vascular smooth muscle and protects myocardium against infarction. Its low phosphodiesterase III inhibiting activity is probably not responsible for its positive inotropic, lusitropic and dilating effects. Unlike other cardiotonic drugs, levosimendan is able to produce positive inotropic effects without prolonging myocardial relaxation or increasing the incidence of malignant arrythmias. It was clinically shown to have a lower risk of mortality in patients with heart failure when compared to placebo and dobutamine. Since it has a larger potential, levosimendan is currently under further clinical evaluation as a chronic treatment for congestive heart failure. |
| Safety Data | Back Directory | [Hazard Codes ]
Xn | [Risk Statements ]
20/21/22 | [Safety Statements ]
36/37 | [WGK Germany ]
3 | [RTECS ]
TY1570210 | [HS Code ]
2933.99.7500 | [Toxicity]
LD50 in male, female mice, male rats (mg/kg): 156, 152, 103 orally; 32, 50, 57 i.v. (Pagel) |
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