levosimendan 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
cardiac stimulants, pimobendan derivatives 1576 141505-33-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • levosimendan
  • (R)-Simendan
  • simdax
A hydrazone and pyridazine derivative; the levo-form is a phosphodiesterase III inhibitor, calcium-sensitizing agent, and inotropic agent that is used in the treatment of HEART FAILURE.
  • Molecular weight: 280.29
  • Formula: C14H12N6O
  • CLOGP: 1.90
  • LIPINSKI: 0
  • HAC: 7
  • HDO: 2
  • TPSA: 113.43
  • ALOGS: -3.50
  • ROTB: 3

Drug dosage:

DoseUnitRoute
11 mg P

ADMET properties:

PropertyValueReference
BA (Bioavailability) 85 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.24 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 3.80 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.02 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 1.10 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
kinase-safety-class ACVR2A,ACVR2B,ACVRL1,AKT2,ALK,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK4,CDK5,CDK9,DDR1,DYRK1B,EGFR,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,GRK3,GSK3B,ITK,JAK1,JAK2,MAP2K6,MAP3K14,MAP3K21,MAP3K7,MAP4K1,MAPK1,MAPK10,MAPK12,MAPK7,MAPK9,MARK4,MELK,MET,MTOR,NTRK2,PDK1,PDK2,PDK4,PDPK1,PIK3CB,PIK3CD,PIM1,PIM2,PIM3,PLK1,PLK2,PLK3,PLK4,PRKCD,PRKDC,SIK2,SIK3,STK33,SYK,TEK,TTK,ULK1 64
kinase-selectivity-class AXL,CAMK2D,CDK9,EIF2AK3,GRK2,MAP2K6,MAP3K14,MAPK7,STK33,TEK,TTK 11
pfas-class PFAS structural alert (1 = True, 0 = False) 0

Approvals:

None

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Lymphatic fistula 213.77 102.87 37 2599 1424 90624387
Femoral hernia incarcerated 212.60 102.87 37 2599 1471 90624340
Wound infection pseudomonas 201.74 102.87 37 2599 1986 90623825
Pancreatic steatosis 196.17 102.87 35 2601 1607 90624204
Arterial haemorrhage 193.58 102.87 37 2599 2486 90623325
Seroma 180.43 102.87 36 2600 3024 90622787
Haemarthrosis 170.87 102.87 36 2600 3958 90621853
Aortic valve stenosis 168.72 102.87 36 2600 4204 90621607
Tachyarrhythmia 160.01 102.87 36 2600 5370 90620441
Hepatic cyst 158.30 102.87 37 2599 6531 90619280
Diverticulum intestinal 156.09 102.87 39 2597 9103 90616708
Eructation 154.19 102.87 40 2596 10842 90614969
Wound dehiscence 151.99 102.87 35 2601 5787 90620024
Faecaloma 146.13 102.87 38 2598 10393 90615418
Inflammatory marker increased 145.85 102.87 37 2599 9177 90616634
Groin pain 144.88 102.87 39 2597 12174 90613637
Aortic arteriosclerosis 142.33 102.87 35 2601 7649 90618162
Cardiovascular disorder 136.44 102.87 38 2598 13454 90612357
Cardiogenic shock 134.41 102.87 43 2593 24425 90601386
Left ventricular dysfunction 133.29 102.87 38 2598 14631 90611180
Postoperative wound infection 132.04 102.87 37 2599 13389 90612422
Escherichia infection 130.28 102.87 38 2598 15857 90609954
Aplastic anaemia 127.91 102.87 36 2600 13233 90612578
Mitral valve incompetence 125.42 102.87 40 2596 22484 90603327
Anuria 123.98 102.87 36 2600 14782 90611029
Tricuspid valve incompetence 119.66 102.87 36 2600 16695 90609116
Osteopenia 108.38 102.87 36 2600 22966 90602845
Myelodysplastic syndrome 107.69 102.87 35 2601 20868 90604943
Pulmonary hypertension 107.61 102.87 42 2594 42481 90583330
Hiatus hernia 104.94 102.87 36 2600 25325 90600486
Haematuria 104.55 102.87 39 2597 34898 90590913

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Jugular vein distension 73.95 64.14 12 574 672 42620077

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Lymphatic fistula 215.69 83.04 37 2945 1458 110584859
Femoral hernia incarcerated 215.34 83.04 37 2945 1472 110584845
Wound infection pseudomonas 198.03 83.04 37 2945 2374 110583943
Pancreatic steatosis 195.16 83.04 35 2947 1787 110584530
Arterial haemorrhage 181.05 83.04 37 2945 3782 110582535
Seroma 180.40 83.04 36 2946 3265 110583052
Aortic valve stenosis 156.93 83.04 36 2946 6314 110580003
Hepatic cyst 154.81 83.04 37 2945 7746 110578571
Haemarthrosis 151.79 83.04 36 2946 7293 110579024
Diverticulum intestinal 149.38 83.04 39 2943 11680 110574637
Tachyarrhythmia 147.51 83.04 36 2946 8225 110578092
Eructation 147.00 83.04 40 2942 14017 110572300
Wound dehiscence 143.71 83.04 35 2947 7927 110578390
Groin pain 138.75 83.04 39 2943 15389 110570928
Faecaloma 135.50 83.04 38 2944 14870 110571447
Aortic arteriosclerosis 132.67 83.04 35 2947 10903 110575414
Inflammatory marker increased 132.05 83.04 37 2945 14432 110571885
Postoperative wound infection 128.93 83.04 37 2945 15716 110570601
Mitral valve incompetence 128.42 83.04 44 2938 33285 110553032
Cardiogenic shock 125.76 83.04 50 2932 57288 110529029
Left ventricular dysfunction 122.57 83.04 39 2943 23454 110562863
Cardiovascular disorder 119.63 83.04 38 2944 22722 110563595
Escherichia infection 117.94 83.04 38 2944 23778 110562539
Osteopenia 112.28 83.04 36 2946 22173 110564144
Tricuspid valve incompetence 109.72 83.04 36 2946 23837 110562480
Aplastic anaemia 109.08 83.04 36 2946 24272 110562045
Anuria 109.03 83.04 36 2946 24305 110562012
Joint dislocation 108.22 83.04 39 2943 34151 110552166
Hiatus hernia 104.59 83.04 36 2946 27570 110558747
Pulmonary hypertension 100.03 83.04 42 2940 55178 110531139
Myelodysplastic syndrome 90.27 83.04 35 2947 37449 110548868

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC C01CX08 CARDIOVASCULAR SYSTEM
CARDIAC THERAPY
CARDIAC STIMULANTS EXCL. CARDIAC GLYCOSIDES
Other cardiac stimulants
MeSH PA D002316 Cardiotonic Agents
MeSH PA D002317 Cardiovascular Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D010726 Phosphodiesterase Inhibitors
MeSH PA D014665 Vasodilator Agents
MeSH PA D020011 Protective Agents
MeSH PA D058987 Phosphodiesterase 3 Inhibitors
CHEBI has role CHEBI:22587 antiviral agent
CHEBI has role CHEBI:35554 cardiovascular drug
CHEBI has role CHEBI:35620 vasodilator agent
CHEBI has role CHEBI:38070 anti-arrhythmia drug
CHEBI has role CHEBI:38147 cardiotonic drug
CHEBI has role CHEBI:50568 EC 3.1.4.17 (3,5-cyclic-nucleotide phosphodiesterase) inhibitor
CHEBI has role CHEBI:231911 renoprotective agent

Related Drugs by ATC class:

C01CX Other cardiac stimulants 3 drugs
angiotensinamideangiotensin IIxamoterol

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Congestive heart failure indication 42343007 DOID:6000




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 6.04 acidic
pKa2 11.34 acidic
pKa3 4.67 Basic
pKa4 4.04 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Troponin C, slow skeletal and cardiac muscles Cytosolic other OPENER Kd 3.16 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
cGMP-inhibited 3',5'-cyclic phosphodiesterase A Enzyme WOMBAT-PK
ATP-sensitive inward rectifier potassium channel 11 Ion channel WOMBAT-PK
ATP-sensitive inward rectifier potassium channel 8 Ion channel WOMBAT-PK

External reference:

IDSource
D04720 KEGG_DRUG
C0246904 UMLSCUI
CHEBI:50567 CHEBI
CHEMBL2051955 ChEMBL_ID
DB00922 DRUGBANK_ID
D000077464 MESH_DESCRIPTOR_UI
3033825 PUBCHEM_CID
7020 INN_ID
C6T4514L4E UNII
73107 RXNORM
009718 NDDF
442790008 SNOMEDCT_US
442795003 SNOMEDCT_US
C6T4514L4E INXIGHT DRUGS

Pharmaceutical products:

None