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Identification
NameLevosimendan
Accession NumberDB00922  (APRD01296)
TypeSmall Molecule
GroupsApproved, Investigational
DescriptionLevosimendan 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.
Structure
Thumb
Synonyms
Levosimedan
Levosimendanum
Simdax
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
SimdaxNot Available
SimendanNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIC6T4514L4E
CAS number141505-33-1
WeightAverage: 280.2847
Monoisotopic: 280.107259036
Chemical FormulaC14H12N6O
InChI KeyWHXMKTBCFHIYNQ-SECBINFHSA-N
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
IUPAC Name
1-cyano-N-{4-[(4R)-4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl]phenyl}methanecarbohydrazonoyl cyanide
SMILES
C[C@@H]1CC(=O)NN=C1C1=CC=C(NN=C(C#N)C#N)C=C1
Pharmacology
IndicationFor short term treatment of acutely decompensated severe chronic heart failure (CHF). Also being investigated for use/treatment in heart disease.
Structured Indications Not Available
PharmacodynamicsLevosimendan 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.
Mechanism of actionLevosimendan 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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Troponin C, slow skeletal and cardiac musclesProteinyes
potentiator
HumanP63316 details
ATP-sensitive inward rectifier potassium channel 11Proteinyes
inducer
HumanQ14654 details
ATP-sensitive inward rectifier potassium channel 8Proteinyes
inducer
HumanQ15842 details
cGMP-inhibited 3',5'-cyclic phosphodiesterase AProteinunknown
inhibitor
HumanQ14432 details
Related Articles
AbsorptionThe bioavailability of oral levosimendan is 85 ± 6% in healthy volunteers and 84 ± 4% in patients.
Volume of distributionNot Available
Protein binding98% bound to plasma protein.
Metabolism

Complete metabolism, with some active metabolites (OR-1855 and OR-1896) possibly extending the drug's haemodynamic effects.

SubstrateEnzymesProduct
Levosimendan
Not Available
OR-1855Details
Levosimendan
Not Available
OR-1896Details
Route of eliminationNot Available
Half lifeEliminination half-life is approximately 1 hour.
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcebutololThe risk or severity of adverse effects can be increased when Acebutolol is combined with Levosimendan.Approved
AcetazolamideThe risk or severity of adverse effects can be increased when Levosimendan is combined with Acetazolamide.Approved, Vet Approved
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Levosimendan.Approved
AliskirenThe risk or severity of adverse effects can be increased when Aliskiren is combined with Levosimendan.Approved, Investigational
AmifostineThe risk or severity of adverse effects can be increased when Amifostine is combined with Levosimendan.Approved, Investigational
AmilorideThe risk or severity of adverse effects can be increased when Amiloride is combined with Levosimendan.Approved
AmiodaroneThe risk or severity of adverse effects can be increased when Amiodarone is combined with Levosimendan.Approved, Investigational
AmlodipineThe risk or severity of adverse effects can be increased when Amlodipine is combined with Levosimendan.Approved
AmobarbitalAmobarbital may increase the hypotensive activities of Levosimendan.Approved, Illicit
Amphotericin BThe risk or severity of adverse effects can be increased when Amphotericin B is combined with Levosimendan.Approved, Investigational
Amyl NitriteThe risk or severity of adverse effects can be increased when Amyl Nitrite is combined with Levosimendan.Approved
ApomorphineThe risk or severity of adverse effects can be increased when Apomorphine is combined with Levosimendan.Approved, Investigational
ApraclonidineThe risk or severity of adverse effects can be increased when Apraclonidine is combined with Levosimendan.Approved
AripiprazoleAripiprazole may increase the hypotensive activities of Levosimendan.Approved, Investigational
ArotinololThe risk or severity of adverse effects can be increased when Arotinolol is combined with Levosimendan.Approved
Arsenic trioxideThe risk or severity of adverse effects can be increased when Arsenic trioxide is combined with Levosimendan.Approved, Investigational
AtenololThe risk or severity of adverse effects can be increased when Atenolol is combined with Levosimendan.Approved
Azilsartan medoxomilThe risk or severity of adverse effects can be increased when Azilsartan medoxomil is combined with Levosimendan.Approved
BarbexacloneBarbexaclone may increase the hypotensive activities of Levosimendan.Experimental
BarbitalBarbital may increase the hypotensive activities of Levosimendan.Illicit
BarnidipineThe risk or severity of adverse effects can be increased when Barnidipine is combined with Levosimendan.Approved
BenazeprilThe risk or severity of adverse effects can be increased when Benazepril is combined with Levosimendan.Approved, Investigational
BendroflumethiazideThe risk or severity of adverse effects can be increased when Bendroflumethiazide is combined with Levosimendan.Approved
BepridilThe risk or severity of adverse effects can be increased when Bepridil is combined with Levosimendan.Approved, Withdrawn
BetaxololThe risk or severity of adverse effects can be increased when Betaxolol is combined with Levosimendan.Approved
BisoprololThe risk or severity of adverse effects can be increased when Bisoprolol is combined with Levosimendan.Approved
BortezomibThe risk or severity of adverse effects can be increased when Bortezomib is combined with Levosimendan.Approved, Investigational
BretyliumThe risk or severity of adverse effects can be increased when Bretylium is combined with Levosimendan.Approved
BrimonidineThe risk or severity of adverse effects can be increased when Brimonidine is combined with Levosimendan.Approved
BromocriptineThe risk or severity of adverse effects can be increased when Bromocriptine is combined with Levosimendan.Approved, Investigational
BumetanideThe risk or severity of adverse effects can be increased when Bumetanide is combined with Levosimendan.Approved
BupivacaineThe risk or severity of adverse effects can be increased when Bupivacaine is combined with Levosimendan.Approved, Investigational
CanagliflozinThe risk or severity of adverse effects can be increased when Canagliflozin is combined with Levosimendan.Approved
CandesartanThe risk or severity of adverse effects can be increased when Candesartan is combined with Levosimendan.Approved
CaptoprilThe risk or severity of adverse effects can be increased when Captopril is combined with Levosimendan.Approved
CarbetocinThe risk or severity of adverse effects can be increased when Carbetocin is combined with Levosimendan.Approved
CarteololThe risk or severity of adverse effects can be increased when Carteolol is combined with Levosimendan.Approved
CarvedilolThe risk or severity of adverse effects can be increased when Carvedilol is combined with Levosimendan.Approved, Investigational
ChlorothiazideThe risk or severity of adverse effects can be increased when Chlorothiazide is combined with Levosimendan.Approved, Vet Approved
ChlorpromazineThe risk or severity of adverse effects can be increased when Chlorpromazine is combined with Levosimendan.Approved, Vet Approved
ChlorthalidoneThe risk or severity of adverse effects can be increased when Chlorthalidone is combined with Levosimendan.Approved
CilazaprilThe risk or severity of adverse effects can be increased when Cilazapril is combined with Levosimendan.Approved
CilnidipineThe risk or severity of adverse effects can be increased when Cilnidipine is combined with Levosimendan.Approved
ClevidipineThe risk or severity of adverse effects can be increased when Clevidipine is combined with Levosimendan.Approved
ClofarabineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Levosimendan.Approved, Investigational
ClomipramineThe risk or severity of adverse effects can be increased when Clomipramine is combined with Levosimendan.Approved, Vet Approved
ClonidineThe risk or severity of adverse effects can be increased when Clonidine is combined with Levosimendan.Approved
ClozapineThe risk or severity of adverse effects can be increased when Clozapine is combined with Levosimendan.Approved
ConivaptanThe risk or severity of adverse effects can be increased when Conivaptan is combined with Levosimendan.Approved, Investigational
DapagliflozinThe risk or severity of adverse effects can be increased when Dapagliflozin is combined with Levosimendan.Approved
DesfluraneThe risk or severity of adverse effects can be increased when Desflurane is combined with Levosimendan.Approved
DexmedetomidineThe risk or severity of adverse effects can be increased when Dexmedetomidine is combined with Levosimendan.Approved, Vet Approved
DiclofenamideThe risk or severity of adverse effects can be increased when Diclofenamide is combined with Levosimendan.Approved
DiltiazemThe risk or severity of adverse effects can be increased when Diltiazem is combined with Levosimendan.Approved
DinutuximabThe risk or severity of adverse effects can be increased when Dinutuximab is combined with Levosimendan.Approved
DipyridamoleThe risk or severity of adverse effects can be increased when Dipyridamole is combined with Levosimendan.Approved
DoxazosinThe risk or severity of adverse effects can be increased when Doxazosin is combined with Levosimendan.Approved
DuloxetineLevosimendan may increase the orthostatic hypotensive activities of Duloxetine.Approved
EfonidipineThe risk or severity of adverse effects can be increased when Efonidipine is combined with Levosimendan.Approved
EmpagliflozinThe risk or severity of adverse effects can be increased when Empagliflozin is combined with Levosimendan.Approved
EnalaprilThe risk or severity of adverse effects can be increased when Enalapril is combined with Levosimendan.Approved, Vet Approved
EnalaprilatThe risk or severity of adverse effects can be increased when Enalaprilat is combined with Levosimendan.Approved
EplerenoneThe risk or severity of adverse effects can be increased when Eplerenone is combined with Levosimendan.Approved
EpoprostenolThe risk or severity of adverse effects can be increased when Epoprostenol is combined with Levosimendan.Approved
EprosartanThe risk or severity of adverse effects can be increased when Eprosartan is combined with Levosimendan.Approved
EsmololThe risk or severity of adverse effects can be increased when Esmolol is combined with Levosimendan.Approved
Etacrynic acidThe risk or severity of adverse effects can be increased when Etacrynic acid is combined with Levosimendan.Approved
FelodipineThe risk or severity of adverse effects can be increased when Felodipine is combined with Levosimendan.Approved, Investigational
FenoldopamThe risk or severity of adverse effects can be increased when Fenoldopam is combined with Levosimendan.Approved
FimasartanThe risk or severity of adverse effects can be increased when Fimasartan is combined with Levosimendan.Approved
FosinoprilThe risk or severity of adverse effects can be increased when Fosinopril is combined with Levosimendan.Approved
FurosemideThe risk or severity of adverse effects can be increased when Furosemide is combined with Levosimendan.Approved, Vet Approved
GuanfacineThe risk or severity of adverse effects can be increased when Guanfacine is combined with Levosimendan.Approved, Investigational
HalothaneThe risk or severity of adverse effects can be increased when Halothane is combined with Levosimendan.Approved, Vet Approved
HexobarbitalHexobarbital may increase the hypotensive activities of Levosimendan.Approved
HydralazineThe risk or severity of adverse effects can be increased when Hydralazine is combined with Levosimendan.Approved
HydrochlorothiazideThe risk or severity of adverse effects can be increased when Hydrochlorothiazide is combined with Levosimendan.Approved, Vet Approved
HydroflumethiazideThe risk or severity of adverse effects can be increased when Hydroflumethiazide is combined with Levosimendan.Approved
IloprostThe risk or severity of adverse effects can be increased when Iloprost is combined with Levosimendan.Approved, Investigational
ImidaprilThe risk or severity of adverse effects can be increased when Imidapril is combined with Levosimendan.Investigational
ImipramineThe risk or severity of adverse effects can be increased when Imipramine is combined with Levosimendan.Approved
IndapamideThe risk or severity of adverse effects can be increased when Indapamide is combined with Levosimendan.Approved
IndoraminThe risk or severity of adverse effects can be increased when Indoramin is combined with Levosimendan.Withdrawn
IrbesartanThe risk or severity of adverse effects can be increased when Irbesartan is combined with Levosimendan.Approved, Investigational
IsocarboxazidThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Levosimendan.Approved
IsofluraneThe risk or severity of adverse effects can be increased when Isoflurane is combined with Levosimendan.Approved, Vet Approved
Isosorbide DinitrateThe risk or severity of adverse effects can be increased when Isosorbide Dinitrate is combined with Levosimendan.Approved
Isosorbide MononitrateThe risk or severity of adverse effects can be increased when Isosorbide Mononitrate is combined with Levosimendan.Approved
IsoxsuprineThe risk or severity of adverse effects can be increased when Isoxsuprine is combined with Levosimendan.Approved, Withdrawn
IsradipineThe risk or severity of adverse effects can be increased when Isradipine is combined with Levosimendan.Approved
LabetalolThe risk or severity of adverse effects can be increased when Labetalol is combined with Levosimendan.Approved
LacidipineThe risk or severity of adverse effects can be increased when Lacidipine is combined with Levosimendan.Approved
LercanidipineThe risk or severity of adverse effects can be increased when Lercanidipine is combined with Levosimendan.Approved, Investigational
LevobunololThe risk or severity of adverse effects can be increased when Levobunolol is combined with Levosimendan.Approved
LevobupivacaineThe risk or severity of adverse effects can be increased when Levobupivacaine is combined with Levosimendan.Approved
LevodopaLevosimendan may increase the orthostatic hypotensive activities of Levodopa.Approved
LisinoprilThe risk or severity of adverse effects can be increased when Lisinopril is combined with Levosimendan.Approved, Investigational
LofexidineThe risk or severity of adverse effects can be increased when Levosimendan is combined with Lofexidine.Approved, Investigational
LosartanThe risk or severity of adverse effects can be increased when Losartan is combined with Levosimendan.Approved
MannitolThe risk or severity of adverse effects can be increased when Mannitol is combined with Levosimendan.Approved, Investigational
MecamylamineThe risk or severity of adverse effects can be increased when Mecamylamine is combined with Levosimendan.Approved
MethazolamideThe risk or severity of adverse effects can be increased when Methazolamide is combined with Levosimendan.Approved
MethohexitalMethohexital may increase the hypotensive activities of Levosimendan.Approved
MethyclothiazideThe risk or severity of adverse effects can be increased when Methyclothiazide is combined with Levosimendan.Approved
MethyldopaThe risk or severity of adverse effects can be increased when Methyldopa is combined with Levosimendan.Approved
MethylphenobarbitalMethylphenobarbital may increase the hypotensive activities of Levosimendan.Approved
MetipranololThe risk or severity of adverse effects can be increased when Metipranolol is combined with Levosimendan.Approved
MetolazoneThe risk or severity of adverse effects can be increased when Metolazone is combined with Levosimendan.Approved
MetoprololThe risk or severity of adverse effects can be increased when Metoprolol is combined with Levosimendan.Approved, Investigational
MinoxidilThe risk or severity of adverse effects can be increased when Minoxidil is combined with Levosimendan.Approved
MoexiprilThe risk or severity of adverse effects can be increased when Moexipril is combined with Levosimendan.Approved
MorphineThe risk or severity of adverse effects can be increased when Levosimendan is combined with Morphine.Approved, Investigational
MoxonidineThe risk or severity of adverse effects can be increased when Levosimendan is combined with Moxonidine.Approved
NabiloneThe risk or severity of adverse effects can be increased when Levosimendan is combined with Nabilone.Approved, Investigational
NadololThe risk or severity of adverse effects can be increased when Nadolol is combined with Levosimendan.Approved
NebivololThe risk or severity of adverse effects can be increased when Nebivolol is combined with Levosimendan.Approved, Investigational
NesiritideThe risk or severity of adverse effects can be increased when Nesiritide is combined with Levosimendan.Approved, Investigational
NicardipineThe risk or severity of adverse effects can be increased when Nicardipine is combined with Levosimendan.Approved
NicorandilNicorandil may increase the hypotensive activities of Levosimendan.Approved
NifedipineThe risk or severity of adverse effects can be increased when Nifedipine is combined with Levosimendan.Approved
NilvadipineThe risk or severity of adverse effects can be increased when Levosimendan is combined with Nilvadipine.Approved
NimodipineThe risk or severity of adverse effects can be increased when Nimodipine is combined with Levosimendan.Approved
NisoldipineThe risk or severity of adverse effects can be increased when Nisoldipine is combined with Levosimendan.Approved
NitrendipineThe risk or severity of adverse effects can be increased when Levosimendan is combined with Nitrendipine.Approved
Nitric OxideThe risk or severity of adverse effects can be increased when Levosimendan is combined with Nitric Oxide.Approved
NitroglycerinThe risk or severity of adverse effects can be increased when Nitroglycerin is combined with Levosimendan.Approved, Investigational
NitroprussideThe risk or severity of adverse effects can be increased when Nitroprusside is combined with Levosimendan.Approved
ObinutuzumabThe risk or severity of adverse effects can be increased when Levosimendan is combined with Obinutuzumab.Approved
OlmesartanThe risk or severity of adverse effects can be increased when Olmesartan is combined with Levosimendan.Approved, Investigational
OxprenololThe risk or severity of adverse effects can be increased when Levosimendan is combined with Oxprenolol.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Levosimendan is combined with Paclitaxel.Approved, Vet Approved
PapaverineThe risk or severity of adverse effects can be increased when Papaverine is combined with Levosimendan.Approved
PenbutololThe risk or severity of adverse effects can be increased when Penbutolol is combined with Levosimendan.Approved, Investigational
PentobarbitalPentobarbital may increase the hypotensive activities of Levosimendan.Approved, Vet Approved
PerindoprilThe risk or severity of adverse effects can be increased when Perindopril is combined with Levosimendan.Approved
PhenelzineThe risk or severity of adverse effects can be increased when Levosimendan is combined with Phenelzine.Approved
PhenobarbitalPhenobarbital may increase the hypotensive activities of Levosimendan.Approved
PhenoxybenzamineThe risk or severity of adverse effects can be increased when Levosimendan is combined with Phenoxybenzamine.Approved
PhentolamineThe risk or severity of adverse effects can be increased when Levosimendan is combined with Phentolamine.Approved
PindololThe risk or severity of adverse effects can be increased when Pindolol is combined with Levosimendan.Approved
PipamperoneThe risk or severity of adverse effects can be increased when Levosimendan is combined with Pipamperone.Approved
PramipexoleThe risk or severity of adverse effects can be increased when Levosimendan is combined with Pramipexole.Approved, Investigational
PrazosinThe risk or severity of adverse effects can be increased when Prazosin is combined with Levosimendan.Approved
PrimidonePrimidone may increase the hypotensive activities of Levosimendan.Approved, Vet Approved
PropofolThe risk or severity of adverse effects can be increased when Levosimendan is combined with Propofol.Approved, Investigational, Vet Approved
PropranololThe risk or severity of adverse effects can be increased when Propranolol is combined with Levosimendan.Approved, Investigational
QuetiapineThe risk or severity of adverse effects can be increased when Quetiapine is combined with Levosimendan.Approved
QuinaprilThe risk or severity of adverse effects can be increased when Quinapril is combined with Levosimendan.Approved, Investigational
RamiprilThe risk or severity of adverse effects can be increased when Ramipril is combined with Levosimendan.Approved
RasagilineThe risk or severity of adverse effects can be increased when Levosimendan is combined with Rasagiline.Approved
RemifentanilThe risk or severity of adverse effects can be increased when Levosimendan is combined with Remifentanil.Approved
ReserpineThe risk or severity of adverse effects can be increased when Reserpine is combined with Levosimendan.Approved
RiociguatThe risk or severity of adverse effects can be increased when Riociguat is combined with Levosimendan.Approved
RisperidoneLevosimendan may increase the hypotensive activities of Risperidone.Approved, Investigational
RopiniroleThe risk or severity of adverse effects can be increased when Levosimendan is combined with Ropinirole.Approved, Investigational
RopivacaineThe risk or severity of adverse effects can be increased when Levosimendan is combined with Ropivacaine.Approved
RotigotineThe risk or severity of adverse effects can be increased when Levosimendan is combined with Rotigotine.Approved
SacubitrilThe risk or severity of adverse effects can be increased when Levosimendan is combined with Sacubitril.Approved
SecobarbitalSecobarbital may increase the hypotensive activities of Levosimendan.Approved, Vet Approved
SelegilineThe risk or severity of adverse effects can be increased when Levosimendan is combined with Selegiline.Approved, Investigational, Vet Approved
SevofluraneThe risk or severity of adverse effects can be increased when Levosimendan is combined with Sevoflurane.Approved, Vet Approved
Sodium NitriteThe risk or severity of adverse effects can be increased when Levosimendan is combined with Sodium Nitrite.Approved
SotalolThe risk or severity of adverse effects can be increased when Sotalol is combined with Levosimendan.Approved
SpironolactoneThe risk or severity of adverse effects can be increased when Spironolactone is combined with Levosimendan.Approved
StreptokinaseThe risk or severity of adverse effects can be increased when Levosimendan is combined with Streptokinase.Approved
SufentanilThe risk or severity of adverse effects can be increased when Levosimendan is combined with Sufentanil.Approved, Investigational
TamsulosinThe risk or severity of adverse effects can be increased when Levosimendan is combined with Tamsulosin.Approved, Investigational
TelmisartanThe risk or severity of adverse effects can be increased when Telmisartan is combined with Levosimendan.Approved, Investigational
TerazosinThe risk or severity of adverse effects can be increased when Terazosin is combined with Levosimendan.Approved
ThalidomideThe risk or severity of adverse effects can be increased when Levosimendan is combined with Thalidomide.Approved, Investigational, Withdrawn
ThiamylalThiamylal may increase the hypotensive activities of Levosimendan.Approved, Vet Approved
ThiopentalThiopental may increase the hypotensive activities of Levosimendan.Approved, Vet Approved
ThioridazineThe risk or severity of adverse effects can be increased when Levosimendan is combined with Thioridazine.Approved
TimololThe risk or severity of adverse effects can be increased when Timolol is combined with Levosimendan.Approved
TizanidineThe risk or severity of adverse effects can be increased when Tizanidine is combined with Levosimendan.Approved
TolazolineThe risk or severity of adverse effects can be increased when Levosimendan is combined with Tolazoline.Approved, Vet Approved
TolcaponeThe risk or severity of adverse effects can be increased when Levosimendan is combined with Tolcapone.Approved, Withdrawn
TorasemideThe risk or severity of adverse effects can be increased when Torasemide is combined with Levosimendan.Approved
TrandolaprilThe risk or severity of adverse effects can be increased when Trandolapril is combined with Levosimendan.Approved
TranylcypromineThe risk or severity of adverse effects can be increased when Levosimendan is combined with Tranylcypromine.Approved
TretinoinThe risk or severity of adverse effects can be increased when Levosimendan is combined with Tretinoin.Approved, Investigational, Nutraceutical
TriamtereneThe risk or severity of adverse effects can be increased when Triamterene is combined with Levosimendan.Approved
ValsartanThe risk or severity of adverse effects can be increased when Valsartan is combined with Levosimendan.Approved, Investigational
VerapamilThe risk or severity of adverse effects can be increased when Verapamil is combined with Levosimendan.Approved
Food InteractionsNot Available
References
Synthesis Reference

Dharmaraj Ramachandra Rao, Rajendra Narayanrao Kankan, Manjinder Singh Phull, Ashwini Amol Sawant, “Process for Preparing Levosimendan and Intermediates for Use in the Process.” U.S. Patent US20120165524, issued June 28, 2012.

US20120165524
General References
  1. Mebazaa A, Nieminen MS, Packer M, Cohen-Solal A, Kleber FX, Pocock SJ, Thakkar R, Padley RJ, Poder P, Kivikko M: Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial. JAMA. 2007 May 2;297(17):1883-91. [PubMed:17473298 ]
  2. Kasikcioglu HA, Cam N: A review of levosimendan in the treatment of heart failure. Vasc Health Risk Manag. 2006;2(4):389-400. [PubMed:17323593 ]
External Links
ATC CodesC01CX08
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (57.1 KB)
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9764
Blood Brain Barrier+0.9248
Caco-2 permeable+0.5602
P-glycoprotein substrateNon-substrate0.5083
P-glycoprotein inhibitor INon-inhibitor0.5867
P-glycoprotein inhibitor IINon-inhibitor0.9615
Renal organic cation transporterNon-inhibitor0.8403
CYP450 2C9 substrateNon-substrate0.7037
CYP450 2D6 substrateNon-substrate0.8349
CYP450 3A4 substrateSubstrate0.6149
CYP450 1A2 substrateInhibitor0.8301
CYP450 2C9 inhibitorNon-inhibitor0.7083
CYP450 2D6 inhibitorNon-inhibitor0.8979
CYP450 2C19 inhibitorNon-inhibitor0.5965
CYP450 3A4 inhibitorNon-inhibitor0.8412
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5918
Ames testNon AMES toxic0.6333
CarcinogenicityNon-carcinogens0.6764
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6188 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9745
hERG inhibition (predictor II)Non-inhibitor0.854
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0881 mg/mLALOGPS
logP2.69ALOGPS
logP2.16ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)10.53ChemAxon
pKa (Strongest Basic)4.91ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area113.43 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity77.63 m3·mol-1ChemAxon
Polarizability28.67 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylhydrazines. These are compounds containing a phenylhydrazide moiety, which consists of a hydrazide substituent attached to a phenyl group.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenylhydrazines
Direct ParentPhenylhydrazines
Alternative Parents
Substituents
  • Phenylhydrazine
  • Pyridazinone
  • Pyridazine
  • Hydrazone
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Nitrile
  • Carbonitrile
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
potentiator
General Function:
Troponin t binding
Specific Function:
Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components: Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments.
Gene Name:
TNNC1
Uniprot ID:
P63316
Molecular Weight:
18402.36 Da
References
  1. Kleerekoper Q, Putkey JA: Drug binding to cardiac troponin C. J Biol Chem. 1999 Aug 20;274(34):23932-9. [PubMed:10446160 ]
  2. Levijoki J, Pollesello P, Kaivola J, Tilgmann C, Sorsa T, Annila A, Kilpelainen I, Haikala H: Further evidence for the cardiac troponin C mediated calcium sensitization by levosimendan: structure-response and binding analysis with analogs of levosimendan. J Mol Cell Cardiol. 2000 Mar;32(3):479-91. [PubMed:10731446 ]
  3. Sorsa T, Heikkinen S, Abbott MB, Abusamhadneh E, Laakso T, Tilgmann C, Serimaa R, Annila A, Rosevear PR, Drakenberg T, Pollesello P, Kilpelainen I: Binding of levosimendan, a calcium sensitizer, to cardiac troponin C. J Biol Chem. 2001 Mar 23;276(12):9337-43. Epub 2000 Dec 11. [PubMed:11113122 ]
  4. Sorsa T, Pollesello P, Permi P, Drakenberg T, Kilpelainen I: Interaction of levosimendan with cardiac troponin C in the presence of cardiac troponin I peptides. J Mol Cell Cardiol. 2003 Sep;35(9):1055-61. [PubMed:12967628 ]
  5. Lehmann A, Boldt J, Lang J, Isgro F, Blome M: [Is levosimendan an inoprotective drug in patients with acute coronary syndrome undergoing surgical revascularization?]. Anasthesiol Intensivmed Notfallmed Schmerzther. 2003 Sep;38(9):577-82. [PubMed:12975736 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inducer
General Function:
Voltage-gated potassium channel activity
Specific Function:
This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectific...
Gene Name:
KCNJ11
Uniprot ID:
Q14654
Molecular Weight:
43540.375 Da
References
  1. Yildiz O: Vasodilating mechanisms of levosimendan: involvement of K+ channels. J Pharmacol Sci. 2007 May;104(1):1-5. Epub 2007 Apr 24. [PubMed:17452812 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inducer
General Function:
Inward rectifier potassium channel activity
Specific Function:
This potassium channel is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward...
Gene Name:
KCNJ8
Uniprot ID:
Q15842
Molecular Weight:
47967.455 Da
References
  1. Yildiz O: Vasodilating mechanisms of levosimendan: involvement of K+ channels. J Pharmacol Sci. 2007 May;104(1):1-5. Epub 2007 Apr 24. [PubMed:17452812 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Metal ion binding
Specific Function:
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.
Gene Name:
PDE3A
Uniprot ID:
Q14432
Molecular Weight:
124978.06 Da
References
  1. Szilagyi S, Pollesello P, Levijoki J, Haikala H, Bak I, Tosaki A, Borbely A, Edes I, Papp Z: Two inotropes with different mechanisms of action: contractile, PDE-inhibitory and direct myofibrillar effects of levosimendan and enoximone. J Cardiovasc Pharmacol. 2005 Sep;46(3):369-76. [PubMed:16116344 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23