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

Stem definitionDrug idCAS RN
potassium channel blockers 4365 794466-70-9

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • RSD1235
  • vernakalant
  • vernakalant hydrochloride
  • brinavess
  • vernakalant HCl
Vernakalant is an antiarrhythmic medicine that acts preferentially in the atria to prolong atrial refractoriness and to rate-dependently slow impulse conduction. These anti-fibrillatory actions on refractoriness and conduction are thought to suppress re-entry, and are potentiated in the atria during atrial fibrillation. The relative selectivity of vernakalant on atrial versus ventricular refractoriness is postulated to result from the block of currents that are expressed in the atria, but not in the ventricles, as well as the unique electrophysiologic condition of the fibrillating atria. However, blockade of cationic currents, including hERG channels and cardiac voltage-dependent sodium channels, which are present in the ventricles has been documented.
  • Molecular weight: 349.47
  • Formula: C20H31NO4
  • CLOGP: 2.53
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 1
  • TPSA: 51.16
  • ALOGS: -3.35
  • ROTB: 7

Drug dosage:

DoseUnitRoute
0.20 g P

ADMET properties:

PropertyValueReference
Vd (Volume of distribution) 1.80 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 8.29 mL/min/kg Lombardo F, Berellini G, Obach RS
t_half (Half-life) 3.13 hours Lombardo F, Berellini G, Obach RS
BA (Bioavailability) 20 %

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 0.497 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 2.500 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 10.280 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 9.354 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 73.500 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 77.170 % High 1
herg hERG pIC50 4.653 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 5.408 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 23.823 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 67.230 % High 1
kinase-safety-class ACVR2A,ACVR2B,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK4,CDK5,CDK9,EIF2AK3,EPHB4,ERBB2,GRK2,ITK,MAPK7,MET,NTRK2,PDK2,PDK4,PIM2,PRKDC,SIK2,TEK,TGFBR1,ZAP70 26
kinase-selectivity-class AXL,EIF2AK3,EPHB4,ERBB2,GRK2,PDK4,PIK3CD,PRKDC 8
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 2.951 High 1
mh-clint Mouse hepatocyte intrinsic clearance 71.614 High 1
mppb Mouse plasma protein binding (% unbound) 76.810 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 7.430 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 83.930 % High 1
rh-clint Rat hepatocyte intrinsic clearance 73.114 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 90.700 % High 1
rppb Rat plasma protein binding (% unbound) 77.330 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 909.913 uM High 1

Approvals:

DateAgencyCompanyOrphan
Sept. 1, 2010 EMA Cardiome UK Limited

FDA Adverse Event Reporting System (Female)

None

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
Sinus arrest 25.52 22.33 3 3 2153 42619176

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
Sinus arrest 26.35 23.91 3 3 4239 110585054

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC C01BG11 CARDIOVASCULAR SYSTEM
CARDIAC THERAPY
ANTIARRHYTHMICS, CLASS I AND III
Other antiarrhythmics, class I and III
CHEBI has role CHEBI:38070 anti-arrhythmia drug

Related Drugs by ATC class:

C01BG Other antiarrhythmics, class I and III 2 drugs
cibenzolinemoracizine

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

DiseaseRelationSNOMED_IDDOID
Atrial fibrillation indication 49436004 DOID:0060224




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.61 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
Potassium voltage-gated channel subfamily A member 5 Ion channel BLOCKER IC50 4.88 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Sodium channel protein type 5 subunit alpha Ion channel IC50 4.73 CHEMBL
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 5.16 CHEMBL
Potassium voltage-gated channel subfamily D member 2 Ion channel IC50 4.30 CHEMBL

External reference:

IDSource
D06665 KEGG_DRUG
748810-28-8 SECONDARY_CAS_RN
C2001572 UMLSCUI
CHEBI:135956 CHEBI
CHEMBL2111112 ChEMBL_ID
CHEMBL2107383 ChEMBL_ID
DB06217 DRUGBANK_ID
C524581 MESH_SUPPLEMENTAL_RECORD_UI
8733 INN_ID
9G468C8B13 UNII
9930049 PUBCHEM_CID
014756 NDDF
014757 NDDF
18311811000001108 SNOMEDCT_US
698874004 SNOMEDCT_US
9G468C8B13 INXIGHT DRUGS

Pharmaceutical products:

None