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

Stem definitionDrug idCAS RN
class I antiarrhythmics, disopyramide derivatives 926 3737-09-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • disopyramide
  • dicorantil
  • disopyramide phosphate
  • disopyramide tartrate
  • disopyramide monohydrochloride
  • disopyramide hydrochloride
A class I anti-arrhythmic agent (one that interferes directly with the depolarization of the cardiac membrane and thus serves as a membrane-stabilizing agent) with a depressant action on the heart similar to that of guanidine. It also possesses some anticholinergic and local anesthetic properties.
  • Molecular weight: 339.48
  • Formula: C21H29N3O
  • CLOGP: 2.58
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 1
  • TPSA: 59.22
  • ALOGS: -3.84
  • ROTB: 8
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.40 g O
0.40 g P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 1 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 55 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 5.89 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 83 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.52 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 0.90 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.16 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 7 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 -0.078 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 5.105 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 4.477 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 2.917 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 64.800 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 59.270 % High 1
herg hERG pIC50 5.020 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 1.069 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 3.972 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 59.500 % High 1
kinase-safety-class ACVR2A,ACVR2B,AKT2,AXL,BRAF,CAMK2B,CAMK2D,CDK5,CDK9,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,ITK,MAP3K7,MAPK12,MAPK7,NTRK2,PDK2,PDK4,PRKDC,SIK2,SIK3,TEK,TGFBR1 26
kinase-selectivity-class AXL,EIF2AK3,PDK4 3
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 3.758 High 1
mh-clint Mouse hepatocyte intrinsic clearance 24.155 High 1
mppb Mouse plasma protein binding (% unbound) 72.960 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 10.186 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 75.250 % High 1
rh-clint Rat hepatocyte intrinsic clearance 15.241 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 83.330 % High 1
rppb Rat plasma protein binding (% unbound) 67.380 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 864.968 uM High 1

Approvals:

DateAgencyCompanyOrphan
Sept. 1, 1977 FDA GD SEARLE LLC

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
Electrocardiogram QT prolonged 40.55 30.17 17 737 72439 90555254
Left atrial volume increased 40.53 30.17 5 749 62 90627631
Mitral valve stenosis 31.68 30.17 6 748 1353 90626340

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
Torsade de pointes 39.93 33.49 11 532 8583 42612209

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
Electrocardiogram QT prolonged 55.24 28.05 26 1201 108934 110479138
Bradycardia 46.50 28.05 26 1201 155491 110432581
Hypoglycaemia 41.90 28.05 22 1205 116082 110471990
Left atrial volume increased 36.93 28.05 5 1222 98 110587974
Torsade de pointes 34.73 28.05 12 1215 22588 110565484
Atrial fibrillation 30.33 28.05 23 1204 229619 110358453
Mitral valve stenosis 29.76 28.05 6 1221 1396 110586676

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC C01BA03 CARDIOVASCULAR SYSTEM
CARDIAC THERAPY
ANTIARRHYTHMICS, CLASS I AND III
Antiarrhythmics, class Ia
FDA EPC N0000175426 Antiarrhythmic
MeSH PA D000889 Anti-Arrhythmia Agents
MeSH PA D002317 Cardiovascular Agents
MeSH PA D026941 Sodium Channel Blockers
MeSH PA D049990 Membrane Transport Modulators
MeSH PA D061567 Voltage-Gated Sodium Channel Blockers
CHEBI has role CHEBI:35554 cardiovascular drug
CHEBI has role CHEBI:38070 anti-arrhythmia drug

Related Drugs by ATC class:

C01BA Antiarrhythmics, class Ia 7 drugs
ajmalinehydroquinidinelorajmineprajmaliumprocainamidequinidinesparteine

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

DiseaseRelationSNOMED_IDDOID
Ventricular arrhythmia indication 44103008
Paroxysmal supraventricular tachycardia off-label use 67198005
Atrial flutter contraindication 5370000
Hyperkalemia contraindication 14140009
Complete atrioventricular block contraindication 27885002
Hypokalemia contraindication 43339004
Low blood pressure contraindication 45007003
Chronic heart failure contraindication 48447003
Atrial fibrillation contraindication 49436004 DOID:0060224
Myocarditis contraindication 50920009 DOID:820
Acute nephropathy contraindication 58574008
Cardiomyopathy contraindication 85898001 DOID:0050700
Cardiogenic shock contraindication 89138009
Kidney disease contraindication 90708001 DOID:557
Myasthenia gravis contraindication 91637004 DOID:437
Prolonged QT interval contraindication 111975006
Second degree atrioventricular block contraindication 195042002
Decompensated cardiac failure contraindication 195111005
Disease of liver contraindication 235856003 DOID:409
Hypoglycemic disorder contraindication 237630007
Benign prostatic hyperplasia contraindication 266569009
Retention of urine contraindication 267064002
Angle-closure glaucoma contraindication 392291006 DOID:13550
Congenital long QT syndrome contraindication 442917000
Increased Intraocular Pressure after Ocular Procedure contraindication




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 13.71 acidic
pKa2 9.79 Basic
pKa3 4.23 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
Sodium channel protein type 5 subunit alpha Ion channel BLOCKER WOMBAT-PK CHEMBL
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 4.04 WOMBAT-PK
Histamine H1 receptor GPCR Ki 5.57 WOMBAT-PK
Muscarinic acetylcholine receptor M1 GPCR WOMBAT-PK
Muscarinic acetylcholine receptor M2 GPCR WOMBAT-PK
Muscarinic acetylcholine receptor M3 GPCR WOMBAT-PK
G protein-activated inward rectifier potassium channel 4 Ion channel IC50 4.92 WOMBAT-PK
Solute carrier family 22 member 1 Transporter IC50 4.09 CHEMBL
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 Ion channel IC50 3.60 WOMBAT-PK

External reference:

IDSource
4019729 VUID
N0000147821 NUI
D00303 KEGG_DRUG
22059-60-5 SECONDARY_CAS_RN
203178 RXNORM
4017844 VANDF
4019729 VANDF
C0012702 UMLSCUI
CHEBI:4657 CHEBI
DP0 PDB_CHEM_ID
CHEMBL517 ChEMBL_ID
DB00280 DRUGBANK_ID
CHEMBL1201020 ChEMBL_ID
D004206 MESH_DESCRIPTOR_UI
3114 PUBCHEM_CID
7167 IUPHAR_LIGAND_ID
1307 INN_ID
GFO928U8MQ UNII
2690 MMSL
4622 MMSL
d00214 MMSL
000623 NDDF
000624 NDDF
372844004 SNOMEDCT_US
49565007 SNOMEDCT_US
76759004 SNOMEDCT_US
54687-36-4 SECONDARY_CAS_RN
GFO928U8MQ INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Norpace CR HUMAN PRESCRIPTION DRUG LABEL 1 0025-2732 CAPSULE, EXTENDED RELEASE 100 mg ORAL NDA 25 sections
Norpace CR HUMAN PRESCRIPTION DRUG LABEL 1 0025-2742 CAPSULE, EXTENDED RELEASE 150 mg ORAL NDA 25 sections
Norpace HUMAN PRESCRIPTION DRUG LABEL 1 0025-2752 CAPSULE, GELATIN COATED 100 mg ORAL NDA 25 sections
Norpace HUMAN PRESCRIPTION DRUG LABEL 1 0025-2762 CAPSULE, GELATIN COATED 150 mg ORAL NDA 25 sections
Disopyramide Phosphate HUMAN PRESCRIPTION DRUG LABEL 1 0093-3127 CAPSULE 100 mg ORAL ANDA 19 sections
Disopyramide Phosphate HUMAN PRESCRIPTION DRUG LABEL 1 0093-3129 CAPSULE 150 mg ORAL ANDA 19 sections
Disopyramide Phosphate HUMAN PRESCRIPTION DRUG LABEL 1 59762-0386 CAPSULE, GELATIN COATED 100 mg ORAL NDA AUTHORIZED GENERIC 28 sections
Disopyramide Phosphate HUMAN PRESCRIPTION DRUG LABEL 1 59762-0400 CAPSULE, GELATIN COATED 150 mg ORAL NDA AUTHORIZED GENERIC 28 sections
Norpace HUMAN PRESCRIPTION DRUG LABEL 1 68151-0526 CAPSULE, GELATIN COATED 100 mg ORAL NDA 26 sections
Norpace HUMAN PRESCRIPTION DRUG LABEL 1 68151-0527 CAPSULE, GELATIN COATED 150 mg ORAL NDA 26 sections
Disopyramide Phosphate HUMAN PRESCRIPTION DRUG LABEL 1 68151-0528 CAPSULE 150 mg ORAL ANDA 19 sections
Disopyramide Phosphate HUMAN PRESCRIPTION DRUG LABEL 1 68151-3858 CAPSULE 100 mg ORAL ANDA 19 sections
DISOPYRAMIDE PHOSPHATE HUMAN PRESCRIPTION DRUG LABEL 1 75907-026 CAPSULE 150 mg ORAL ANDA 26 sections
DISOPYRAMIDE PHOSPHATE HUMAN PRESCRIPTION DRUG LABEL 1 75907-027 CAPSULE 100 mg ORAL ANDA 26 sections