Tìm theo
Levosimendan
Các tên gọi khác (3) :
  • Levosimedan
  • Levosimendanum
  • Simdax
phosphodiesterase inhibitors, anti arrhythmia agents, cardiotonic agents, vasodilator agents
Thuốc Gốc
Small Molecule
CAS: 141505-33-1
ATC: C01CX08
CTHH: C14H12N6O
PTK: 280.2847
Levosimendan is a calcium sensitiser used in the management of acutely decompensated congestive heart failure. It increases the sensitivity of the heart to calcium, thus increasing cardiac contractility without a rise in intracellular calcium. Levosimendan exerts its effect by increasing calcium sensitivity of myocytes by binding to cardiac troponin C in a calcium-dependent manner. It also has a vasodilatory effect, by opening adenosine triphosphate (ATP)-sensitive potassium channels in vascular smooth muscle to cause smooth muscle relaxation.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C14H12N6O
Phân tử khối
280.2847
Monoisotopic mass
280.107259036
InChI
InChI=1S/C14H12N6O/c1-9-6-13(21)19-20-14(9)10-2-4-11(5-3-10)17-18-12(7-15)8-16/h2-5,9,17H,6H2,1H3,(H,19,21)/t9-/m1/s1
InChI Key
InChIKey=WHXMKTBCFHIYNQ-SECBINFHSA-N
IUPAC Name
1-cyano-N-{4-[(4R)-4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl]phenyl}methanecarbohydrazonoyl cyanide
Traditional IUPAC Name
levosimendan
SMILES
C[C@@H]1CC(=O)NN=C1C1=CC=C(NN=C(C#N)C#N)C=C1
Độ hòa tan
8.81e-02 g/l
logP
2.16
logS
-3.5
pKa (strongest acidic)
10.53
pKa (Strongest Basic)
4.91
PSA
113.43 Å2
Refractivity
77.63 m3·mol-1
Polarizability
28.67 Å3
Rotatable Bond Count
3
H Bond Acceptor Count
6
H Bond Donor Count
2
Physiological Charge
0
Number of Rings
2
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : Levosimendan is a new Ca2+-sensitizing inotropic agent. Ca2+ sensitizers represent a new class of inotropic agents, which overcome the disadvantages associated with currently available inotropic agents in as they are not associated with an increased risk of arrhythmias, cell injury and death due to Ca2+ overload in myocardial cells; they do not increase the activation energy; and they have the potential to reverse contractile dysfunction under pathophysiologic conditions, such as acidosis or myocardial stunning. Levosimendan has not been approved for use in the U.S. or Canada.
Cơ Chế Tác Dụng : Levosimendan is a calcium sensitiser used in the management of acutely decompensated congestive heart failure. It increases the sensitivity of the heart to calcium, thus increasing cardiac contractility without a rise in intracellular calcium. Levosimendan exerts its effect by increasing calcium sensitivity of myocytes by binding to cardiac troponin C in a calcium-dependent manner. It also has a vasodilatory effect, by opening adenosine triphosphate (ATP)-sensitive potassium channels in vascular smooth muscle to cause smooth muscle relaxation. Levosimendan appears to increase myofilament calcium sensitivity by binding to cardiac troponin C in a calcium-dependent manner. This stabilizes the calcium-induced conformational change of troponin C, thereby (1) changing actin-myosin cross-bridge kinetics apparently without increasing the cycling rate of the cross-bridges or myocardial ATP consumption, (2) increasing the effects of calcium on cardiac myofilaments during systole and (3) improving contraction at low energy cost (inotropic effect). Calcium concentration and, therefore, sensitization decline during diastole, allowing normal or improved diastolic relaxation. Levosimendan also leads to vasodilation through the opening of ATP-sensitive potassium channels. By these inotropic and vasodilatory actions, levosimendan increases cardiac output without increasing myocardial oxygen demand. Levosimendan also has a selective phosphodiesterase (PDE)-III inhibitory action that may contribute to the inotropic effect of this compound under certain experimental conditions. It has been reported that levosimendan may act preferentially as a Ca2+ sensitizer at lower concentrations, whereas at higher concentrations its action as a PDE-III inhibitor becomes more prominent in experimental animals and humans.
Dược Động Học :
▧ Absorption :
The bioavailability of oral levosimendan is 85 ± 6% in healthy volunteers and 84 ± 4% in patients.
▧ Protein binding :
98% bound to plasma protein.
▧ Metabolism :
Complete metabolism, with some active metabolites (OR-1855 and OR-1896) possibly extending the drug's haemodynamic effects.
▧ Half Life :
Eliminination half-life is approximately 1 hour.
Chỉ Định : For short term treatment of acutely decompensated severe chronic heart failure (CHF). Also being investigated for use/treatment in heart disease.
Dữ Kiện Thương Mại
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Simdax
  • Công ty :
    Sản phẩm biệt dược : Simendan
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00922
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=3033825
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46507149
ChemSpider
http://www.chemspider.com/Chemical-Structure.2298414.html
PharmGKB
http://www.pharmgkb.org/drug/PA164749138
Wikipedia
http://en.wikipedia.org/wiki/Levosimendan
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