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MedKoo Cat#: 318150 | Name: Levosimendan
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Levosimendan is a calcium sensitizer that can cause increased cardiac contractility by binding troponin C, promotes vasodilation by activating ATP-sensitive potassium channels on vascular smooth muscle cells, 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.

Chemical Structure

Levosimendan
CAS#141505-33-1

Theoretical Analysis

MedKoo Cat#: 318150

Name: Levosimendan

CAS#: 141505-33-1

Chemical Formula: C14H12N6O

Exact Mass: 280.1073

Molecular Weight: 280.28

Elemental Analysis: C, 59.99; H, 4.32; N, 29.98; O, 5.71

Price and Availability

Size Price Availability Quantity
10mg USD 350.00 2 Weeks
50mg USD 550.00 2 Weeks
1g USD 1,450.00 2 Weeks
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Related CAS #
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Synonym
Levosimendan; Simdax; Levosimendanum; Levosimedan; (-)-OR-1259; dextrosimendan; Levosimendan; OR 1259; OR-1259; OR-1855; Simadax; simendan;
IUPAC/Chemical Name
2-[[4-[(4R)-4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl]phenyl]hydrazinylidene]propanedinitrile
InChi Key
WHXMKTBCFHIYNQ-UHFFFAOYSA-N
InChi Code
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)
SMILES Code
CC1CC(=O)NN=C1C2=CC=C(C=C2)NN=C(C#N)C#N
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
Levosimendan (Simsndan; OR-1259) is a calcium sensitiser used in the management of acutely decompensated congestive heart failure.
In vitro activity:
The role of cardiac troponin C (cTnC) as a target protein for the calcium sensitization by levosimendan, pimobendan, MCI-154 and EMD 53998 was evaluated using purified recombinant human cTnC. Only levosimendan showed calcium-dependent and to a lesser extent magnesium-dependent retention in the cTnC column. The findings indicate that levosimendan binds both to the N-terminal and C-terminal domains of cTnC. Reference: J Mol Cell Cardiol. 1995 Sep;27(9):1859-66. https://pubmed.ncbi.nlm.nih.gov/8523447/
In vivo activity:
The electrophysiological effect of levosimendan, a novel Ca(2+)-sensitizing positive inotropic agent and vasodilator, was examined on rat mesenteric arterial myocytes using the patch clamp technique. Resting potential was significantly hyperpolarized with levosimendan, with an EC50 of 2.9 microM and maximal effect (19.5 +/- 3.5 mV; n = 12) at 10 microM. Levosimendan (10 microM) significantly increased the whole-cell outward current. Reference: Eur J Pharmacol. 1997 Aug 27;333(2-3):249-59. https://pubmed.ncbi.nlm.nih.gov/9314042/
Solvent mg/mL mM comments
Solubility
DMF 30.0 107.03
DMSO 43.7 155.79
Ethanol 10.0 36.68
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 280.28 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Gaballah M, Penttinen K, Kreutzer J, Mäki AJ, Kallio P, Aalto-Setälä K. Cardiac Ischemia On-a-Chip: Antiarrhythmic Effect of Levosimendan on Ischemic Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Cells. 2022 Mar 19;11(6):1045. doi: 10.3390/cells11061045. PMID: 35326497; PMCID: PMC8947267. 2. Haikala H, Kaivola J, Nissinen E, Wall P, Levijoki J, Lindén IB. Cardiac troponin C as a target protein for a novel calcium sensitizing drug, levosimendan. J Mol Cell Cardiol. 1995 Sep;27(9):1859-66. doi: 10.1016/0022-2828(95)90009-8. PMID: 8523447. 3. Yokoshiki H, Katsube Y, Sunagawa M, Sperelakis N. Levosimendan, a novel Ca2+ sensitizer, activates the glibenclamide-sensitive K+ channel in rat arterial myocytes. Eur J Pharmacol. 1997 Aug 27;333(2-3):249-59. doi: 10.1016/s0014-2999(97)01108-4. PMID: 9314042. 4. Edes I, Kiss E, Kitada Y, Powers FM, Papp JG, Kranias EG, Solaro RJ. Effects of Levosimendan, a cardiotonic agent targeted to troponin C, on cardiac function and on phosphorylation and Ca2+ sensitivity of cardiac myofibrils and sarcoplasmic reticulum in guinea pig heart. Circ Res. 1995 Jul;77(1):107-13. doi: 10.1161/01.res.77.1.107. PMID: 7788868.
In vitro protocol:
1. Gaballah M, Penttinen K, Kreutzer J, Mäki AJ, Kallio P, Aalto-Setälä K. Cardiac Ischemia On-a-Chip: Antiarrhythmic Effect of Levosimendan on Ischemic Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Cells. 2022 Mar 19;11(6):1045. doi: 10.3390/cells11061045. PMID: 35326497; PMCID: PMC8947267. 2. Haikala H, Kaivola J, Nissinen E, Wall P, Levijoki J, Lindén IB. Cardiac troponin C as a target protein for a novel calcium sensitizing drug, levosimendan. J Mol Cell Cardiol. 1995 Sep;27(9):1859-66. doi: 10.1016/0022-2828(95)90009-8. PMID: 8523447.
In vivo protocol:
1. Yokoshiki H, Katsube Y, Sunagawa M, Sperelakis N. Levosimendan, a novel Ca2+ sensitizer, activates the glibenclamide-sensitive K+ channel in rat arterial myocytes. Eur J Pharmacol. 1997 Aug 27;333(2-3):249-59. doi: 10.1016/s0014-2999(97)01108-4. PMID: 9314042. 2. Edes I, Kiss E, Kitada Y, Powers FM, Papp JG, Kranias EG, Solaro RJ. Effects of Levosimendan, a cardiotonic agent targeted to troponin C, on cardiac function and on phosphorylation and Ca2+ sensitivity of cardiac myofibrils and sarcoplasmic reticulum in guinea pig heart. Circ Res. 1995 Jul;77(1):107-13. doi: 10.1161/01.res.77.1.107. PMID: 7788868.
1: Gürbüzel M, Sayar I, Cankaya M, Gürbüzel A, Demirtas L, Bakirci EM, Capoglu I. The preventive role of levosimendan against bleomycin-induced pulmonary fibrosis in rats. Pharmacol Rep. 2016 Apr;68(2):378-82. doi: 10.1016/j.pharep.2015.10.001. Epub 2015 Oct 23. PubMed PMID: 26922542. 2: Tarkia M, Stark C, Haavisto M, Kentala R, Vähäsilta T, Savunen T, Strandberg M, Saunavaara V, Tolvanen T, Teräs M, Pietilä M, Nyman L, Duvall E, Saukko P, Levijoki J, Roivainen A, Saraste A, Knuuti J. Effect of levosimendan therapy on myocardial infarct size and left ventricular function after acute coronary occlusion. Heart. 2016 Mar;102(6):465-71. doi: 10.1136/heartjnl-2015-308137. Epub 2016 Jan 13. PubMed PMID: 26762238. 3: Zhou C, Gong J, Chen D, Wang W, Liu M, Liu B. Levosimendan for Prevention of Acute Kidney Injury After Cardiac Surgery: A Meta-analysis of Randomized Controlled Trials. Am J Kidney Dis. 2016 Mar;67(3):408-16. doi: 10.1053/j.ajkd.2015.09.015. Epub 2015 Oct 27. PubMed PMID: 26518388. 4: Ertuna E, Turkseven S, Amanvermez D, Ayik F, Yagdi T, Yasa M. Effects of Levosimendan on Isolated Human Internal Mammary Artery and Saphenous Vein: Concurrent Use with Conventional Vasodilators. Fundam Clin Pharmacol. 2016 Feb 3. doi: 10.1111/fcp.12185. [Epub ahead of print] PubMed PMID: 26839979. 5: Sommer S, Leistner M, Aleksic I, Schimmer C, Alhussini K, Kanofsky P, Leyh RG, Sommer SP. Impact of levosimendan and ischaemia-reperfusion injury on myocardial subsarcolemmal mitochondrial respiratory chain, mitochondrial membrane potential, Ca2+ cycling and ATP synthesis†. Eur J Cardiothorac Surg. 2016 Feb;49(2):e54-62. doi: 10.1093/ejcts/ezv397. Epub 2015 Nov 18. PubMed PMID: 26586791. 6: Pollesello P, Parissis J, Kivikko M, Harjola VP. Levosimendan meta-analyses: Is there a pattern in the effect on mortality? Int J Cardiol. 2016 Feb 3;209:77-83. doi: 10.1016/j.ijcard.2016.02.014. [Epub ahead of print] Review. PubMed PMID: 26882190. 7: Pineda-Sanabria SE, Robertson IM, Sun YB, Irving M, Sykes BD. Probing the mechanism of cardiovascular drugs using a covalent levosimendan analog. J Mol Cell Cardiol. 2016 Feb 4;92:174-184. doi: 10.1016/j.yjmcc.2016.02.003. [Epub ahead of print] PubMed PMID: 26853943. 8: Axelsson B, Häggmark S, Svenmarker S, Johansson G, Gupta A, Tydén H, Wouters P, Haney M. Effects of Combined Milrinone and Levosimendan Treatment on Systolic and Diastolic Function During Postischemic Myocardial Dysfunction in a Porcine Model. J Cardiovasc Pharmacol Ther. 2016 Feb 1. pii: 1074248416628675. [Epub ahead of print] PubMed PMID: 26837238. 9: Varvarousi G, Xanthos T, Sarafidou P, Katsioula E, Georgiadou M, Eforakopoulou M, Pavlou H. Role of levosimendan in the management of subarachnoid hemorrhage. Am J Emerg Med. 2016 Feb;34(2):298-306. doi: 10.1016/j.ajem.2015.11.024. Epub 2015 Nov 25. Review. PubMed PMID: 26669277. 10: Sahu MK, Das A, Malik V, Subramanian A, Singh SP, Hote M. Comparison of levosimendan and nitroglycerine in patients undergoing coronary artery bypass graft surgery. Ann Card Anaesth. 2016 Jan-Mar;19(1):52-8. doi: 10.4103/0971-9784.173020. PubMed PMID: 26750674. 11: Mardiguian S, Kivikko M, Heringlake M, Smare C, Bertranou E, Apajasalo M, Pollesello P. Cost-benefits of incorporating levosimendan into cardiac surgery practice: German base case. J Med Econ. 2016 Jan 8:1-8. [Epub ahead of print] PubMed PMID: 26707159. 12: Freixa X, Hernández M, Farrero M, Sitges M, Jiménez G, Regueiro A, Fita G, Tatjer I, Andrea R, Martín-Yuste V, Brugaletta S, Masotti M, Sabaté M. Levosimendan as an adjunctive therapy to MitraClip implantation in patients with severe mitral regurgitation and left ventricular dysfunction. Int J Cardiol. 2016 Jan 1;202:517-8. doi: 10.1016/j.ijcard.2015.09.056. Epub 2015 Sep 25. PubMed PMID: 26440466. 13: Silvetti S, Nieminen MS. Repeated or intermittent levosimendan treatment in advanced heart failure: An updated meta-analysis. Int J Cardiol. 2016 Jan 1;202:138-43. doi: 10.1016/j.ijcard.2015.08.188. Epub 2015 Aug 28. PubMed PMID: 26386941. 14: Guerrero Orriach JL, Galán Ortega M, Ramírez Fernandez A, Ariza Villanueva D, Florez Vela A, Moreno Cortés I, Rubio Navarro M, Cruz Mañas J. Assessing the effect of preoperative levosimendan on renal function in patients with right ventricular dysfunction. J Clin Monit Comput. 2016 Jan 13. [Epub ahead of print] PubMed PMID: 26762127. 15: Schlürmann CN, Reinöhl J, Kalbhenn J. [Levosimendan for septic shock with takotsubo cardiomyopathy]. Anaesthesist. 2016 Jan;65(1):46-9. doi: 10.1007/s00101-015-0114-7. German. PubMed PMID: 26620046. 16: Akhtar MS, Pillai KK, Hassan Q, Ansari SH, Ali J, Akhtar M, Najmi AK. Levosimendan suppresses oxidative injury, apoptotic signaling and mitochondrial degeneration in streptozotocin-induced diabetic cardiomyopathy. Clin Exp Hypertens. 2016 Jan;38(1):10-22. doi: 10.3109/10641963.2015.1047947. Epub 2015 Jul 24. PubMed PMID: 26207881. 17: Hillgaard TK, Andersen A, Andersen S, Vildbrad MD, Ringgaard S, Nielsen JM, Nielsen-Kudsk JE. Levosimendan prevents pressure-overload induced right ventricular failure. J Cardiovasc Pharmacol. 2015 Dec 15. [Epub ahead of print] PubMed PMID: 26674544. 18: Nieto Estrada VH, Molano Franco DL, Valencia Moreno AA, Rojas Gambasica JA, Jaller Bornacelli YE, Martinez Del Valle A. Reversion of Severe Mitral Insufficiency in Peripartum Cardiomyopathy Using Levosimendan. J Clin Med Res. 2015 Dec;7(12):998-1001. doi: 10.14740/jocmr2323w. Epub 2015 Oct 23. PubMed PMID: 26566415; PubMed Central PMCID: PMC4625822. 19: Okada M, Yamawaki H. Levosimendan inhibits interleukin-1β-induced apoptosis through activation of Akt and inhibition of inducible nitric oxide synthase in rat cardiac fibroblasts. Eur J Pharmacol. 2015 Dec 15;769:86-92. doi: 10.1016/j.ejphar.2015.10.056. Epub 2015 Oct 31. PubMed PMID: 26528797. 20: Gong B, Li Z, Yat Wong PC. Levosimendan Treatment for Heart Failure: A Systematic Review and Meta-Analysis. J Cardiothorac Vasc Anesth. 2015 Dec;29(6):1415-25. doi: 10.1053/j.jvca.2015.03.023. Epub 2015 Mar 26. PubMed PMID: 26275522.