levosimendan Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
cardiac stimulants, pimobendan derivatives	1576	141505-33-1

Description:

Molecule

Description

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:

Dose	Unit	Route
11	mg	P

ADMET properties:

Property	Value	Reference
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

Approvals:

None

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Lymphatic fistula	118.58	97.83	21	1409	877	46683755
Femoral hernia incarcerated	118.32	97.83	21	1409	888	46683744
Pancreatic steatosis	116.22	97.83	21	1409	984	46683648
Arterial haemorrhage	111.01	97.83	22	1408	1696	46682936
Wound infection pseudomonas	108.46	97.83	21	1409	1434	46683198
Cardiogenic shock	101.82	97.83	32	1398	16352	46668280
Seroma	100.70	97.83	21	1409	2086	46682546
Haemarthrosis	98.83	97.83	22	1408	2971	46681661
Aortic valve stenosis	97.89	97.83	22	1408	3102	46681530

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event

Pharmacologic Action:

Source	Code	Description
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	D058987	Phosphodiesterase 3 Inhibitors
MeSH PA	D010726	Phosphodiesterase Inhibitors
MeSH PA	D020011	Protective Agents
MeSH PA	D014665	Vasodilator Agents
CHEBI has role	CHEBI:35620	vasodilator
CHEBI has role	CHEBI:38070	antiarrhythmic agent
CHEBI has role	CHEBI:38147	cardiotonic drugs
CHEBI has role	CHEBI:50568	cyclic nucleotide phosphodiesterase inhibitor

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Congestive heart failure	indication	42343007	DOID:6000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (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:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Troponin C, slow skeletal and cardiac muscles	Cytosolic other	P63316	TNNC1_HUMAN	OPENER	Kd	3.15		SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE
ATP-sensitive inward rectifier potassium channel 8	Ion channel	Q15842	KCNJ8_HUMAN					WOMBAT-PK
ATP-sensitive inward rectifier potassium channel 11	Ion channel	Q14654	KCJ11_HUMAN					WOMBAT-PK
cGMP-inhibited 3',5'-cyclic phosphodiesterase A	Enzyme	Q14432	PDE3A_HUMAN					WOMBAT-PK

External reference:

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

Pharmaceutical products:

None