Identification

Name
Disopyramide
Accession Number
DB00280  (APRD00507)
Type
Small Molecule
Groups
Approved
Description

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.

Structure
Thumb
Synonyms
  • Disopiramida
  • Disopyramidum
Product Ingredients
IngredientUNIICASInChI Key
Disopyramide phosphateN6BOM1935W22059-60-5CGDDQFMPGMYYQP-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NorpaceCapsule, gelatin coated150 mg/1OralG.D. Searle LLC Division of Pfizer Inc1977-09-01Not applicableUs
NorpaceCapsule, gelatin coated100 mg/1OralCarilion Materials Management1982-07-20Not applicableUs
NorpaceCapsule, gelatin coated100 mg/1OralG.D. Searle LLC Division of Pfizer Inc1977-09-01Not applicableUs
NorpaceCapsule, gelatin coated150 mg/1OralCarilion Materials Management1982-07-20Not applicableUs
NorpaceCapsule, gelatin coated150 mg/1OralPhysicians Total Care, Inc.1982-07-202012-06-30Us
Norpace Cap 100mgCapsule100 mgOralRoberts Pharmaceutical1994-12-311999-08-11Canada
Norpace Cap 150mgCapsule150 mgOralRoberts Pharmaceutical1994-12-311999-08-11Canada
Norpace CRCapsule, extended release150 mg/1OralG.D. Searle LLC Division of Pfizer Inc1982-07-20Not applicableUs
Norpace CRCapsule, extended release100 mg/1OralG.D. Searle LLC Division of Pfizer Inc1982-07-20Not applicableUs
Norpace CR 150mgTablet, extended release150 mgOralShire Biochem Inc1994-12-312004-04-30Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Disopyramide PhosphateCapsule150 mg/1OralPhysicians Total Care, Inc.1985-05-312002-06-30Us
Disopyramide PhosphateCapsule100 mg/1OralMayne Pharma Inc.2018-07-02Not applicableUs
Disopyramide PhosphateCapsule100 mg/1OralMed Pharma Co., Ltd.2011-07-052012-07-18Us
Disopyramide PhosphateCapsule150 mg/1OralGsms, Incorporated2018-01-12Not applicableUs
Disopyramide PhosphateCapsule150 mg/1OralAv Kare, Inc.2014-01-03Not applicableUs
Disopyramide PhosphateCapsule100 mg/1OralMayne Pharma2016-08-03Not applicableUs
Disopyramide PhosphateCapsule150 mg/1OralActavis Pharma Company1985-05-31Not applicableUs
Disopyramide PhosphateCapsule100 mg/1OralPhysicians Total Care, Inc.1985-05-312012-06-30Us
Disopyramide PhosphateCapsule150 mg/1OralTeva Pharmaceuticals USA, Inc.1990-09-30Not applicableUs00093 3129 01 nlmimage10 b32dd9fe
Disopyramide PhosphateCapsule100 mg/1OralAv Kare, Inc.2014-01-03Not applicableUs
International/Other Brands
Dicorantil (Sanofi) / Isorythm (SERP) / Lispine (Sawai Seiyaku) / Ritmodan (Sanofi)
Categories
UNII
GFO928U8MQ
CAS number
3737-09-5
Weight
Average: 339.4745
Monoisotopic: 339.231062565
Chemical Formula
C21H29N3O
InChI Key
UVTNFZQICZKOEM-UHFFFAOYSA-N
InChI
InChI=1S/C21H29N3O/c1-16(2)24(17(3)4)15-13-21(20(22)25,18-10-6-5-7-11-18)19-12-8-9-14-23-19/h5-12,14,16-17H,13,15H2,1-4H3,(H2,22,25)
IUPAC Name
4-[bis(propan-2-yl)amino]-2-phenyl-2-(pyridin-2-yl)butanamide
SMILES
CC(C)N(CCC(C(N)=O)(C1=CC=CC=C1)C1=NC=CC=C1)C(C)C

Pharmacology

Indication

For the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, ventricular pre-excitation and cardiac dysrhythmias. It is a Class Ia antiarrhythmic drug.

Associated Conditions
Pharmacodynamics

Disopyramide is an antiarrhythmic drug indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia that are life-threatening. In man, Disopyramide at therapeutic plasma levels shortens the sinus node recovery time, lengthens the effective refractory period of the atrium, and has a minimal effect on the effective refractory period of the AV node. Little effect has been shown on AV-nodal and His-Purkinje conduction times or QRS duration. However, prolongation of conduction in accessory pathways occurs.

Mechanism of action

Disopyramide is a Type 1A antiarrhythmic drug (ie, similar to procainamide and quinidine). It inhibits the fast sodium channels. In animal studies Disopyramide decreases the rate of diastolic depolarization (phase 4) in cells with augmented automaticity, decreases the upstroke velocity (phase 0) and increases the action potential duration of normal cardiac cells, decreases the disparity in refractoriness between infarcted and adjacent normally perfused myocardium, and has no effect on alpha- or beta-adrenergic receptors.

TargetActionsOrganism
ASodium channel protein type 5 subunit alpha
inhibitor
Human
UMuscarinic acetylcholine receptor M1
antagonist
Human
UMuscarinic acetylcholine receptor M2
antagonist
Human
UMuscarinic acetylcholine receptor M3
antagonist
Human
UPotassium voltage-gated channel subfamily D member 2
inhibitor
Human
UPotassium voltage-gated channel subfamily D member 3
inhibitor
Human
UPotassium voltage-gated channel subfamily H member 2
inhibitor
Human
UAlpha-1-acid glycoprotein 2Not AvailableHuman
Absorption

Nearly complete

Volume of distribution
Not Available
Protein binding

50%-65%

Metabolism

Hepatic

Route of elimination

In healthy men, about 50% of a given dose of disopyramide is excreted in the urine as the unchanged drug, about 20% as the mono-N-dealkylated metabolite and 10% as the other metabolites.

Half life

6.7 hours (range 4-10 hours)

Clearance
Not Available
Toxicity

LD50=580 mg/kg in rats

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Disopyramide Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Disopyramide.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Disopyramide.
1,10-PhenanthrolineThe therapeutic efficacy of Disopyramide can be decreased when used in combination with 1,10-Phenanthroline.
2,4-thiazolidinedioneThe risk or severity of hypoglycemia can be increased when Disopyramide is combined with 2,4-thiazolidinedione.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Disopyramide.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Disopyramide.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Disopyramide.
5-(2-methylpiperazine-1-sulfonyl)isoquinolineThe therapeutic efficacy of Disopyramide can be increased when used in combination with 5-(2-methylpiperazine-1-sulfonyl)isoquinoline.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Disopyramide.
6-Deoxyerythronolide B6-Deoxyerythronolide B may increase the QTc-prolonging activities of Disopyramide.
Food Interactions
  • Avoid alcohol.
  • Take without regard to meals.

References

Synthesis Reference

Cusic, J.W. and Sause, H.W.; U.S. Patent 3,225,054; December 21,1965; assigned to G.D. Searle & Co.

US3225054
General References
Not Available
External Links
Human Metabolome Database
HMDB0014425
KEGG Drug
D00303
KEGG Compound
C06965
PubChem Compound
3114
PubChem Substance
46508226
ChemSpider
3002
BindingDB
50028893
ChEBI
4657
ChEMBL
CHEMBL517
Therapeutic Targets Database
DAP000504
PharmGKB
PA449373
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Disopyramide
ATC Codes
C01BA03 — Disopyramide
AHFS Codes
  • 24:04.04.04 — Class IA Antiarrythmics

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentArrythmias / Cardiovascular Disease (CVD) / Heart Diseases / Nonvalvular Atrial Fibrillation1
3TerminatedTreatmentHeart Failure, Unspecified / Nonvalvular Atrial Fibrillation1
Not AvailableActive Not RecruitingTreatmentNonvalvular Atrial Fibrillation / Quality of Life1

Pharmacoeconomics

Manufacturers
  • Kv pharmaceutical co
  • Gd searle llc
  • Interpharm inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Superpharm corp
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
Packagers
  • Amerisource Health Services Corp.
  • Ethex Corp.
  • GD Searle LLC
  • Kaiser Foundation Hospital
  • KV Pharmaceutical Co.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmacia Inc.
  • Physicians Total Care Inc.
  • Sandhills Packaging Inc.
  • Teva Pharmaceutical Industries Ltd.
  • Watson Pharmaceuticals
Dosage forms
FormRouteStrength
CapsuleOral100 mg/1
CapsuleOral150 mg/1
Capsule, gelatin coatedOral100 mg/1
Capsule, gelatin coatedOral150 mg/1
CapsuleOral150 mg
Capsule, extended releaseOral100 mg/1
Capsule, extended releaseOral150 mg/1
Tablet, extended releaseOral150 mg
CapsuleOral100 mg
Tablet, extended releaseOral250 mg
Prices
Unit descriptionCostUnit
Norpace CR 150 mg 12 Hour Capsule2.35USD capsule
Norpace cr 150 mg capsule2.26USD capsule
Norpace CR 100 mg 12 Hour Capsule1.98USD capsule
Norpace 150 mg capsule1.94USD capsule
Norpace cr 100 mg capsule1.91USD capsule
Norpace 100 mg capsule1.62USD capsule
Disopyramide Phosphate 150 mg capsule0.96USD capsule
Disopyramide 150 mg capsule0.82USD capsule
Disopyramide Phosphate 100 mg capsule0.72USD capsule
Disopyramide 100 mg capsule0.69USD capsule
Rythmodan 150 mg Capsule0.43USD capsule
Rythmodan 100 mg Capsule0.3USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)94.5-95 °CCusic, J.W. and Sause, H.W.; U.S. Patent 3,225,054; December 21,1965; assigned to G.D. Searle & Co.
water solubility44.9 mg/LNot Available
logP2.58MANNHOLD,R ET AL. (1993)
Predicted Properties
PropertyValueSource
Water Solubility0.0493 mg/mLALOGPS
logP3.21ALOGPS
logP3.47ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)16.19ChemAxon
pKa (Strongest Basic)10.42ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area59.22 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity102.3 m3·mol-1ChemAxon
Polarizability38.82 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9529
Blood Brain Barrier+0.9508
Caco-2 permeable+0.557
P-glycoprotein substrateSubstrate0.5492
P-glycoprotein inhibitor INon-inhibitor0.8677
P-glycoprotein inhibitor IINon-inhibitor0.8535
Renal organic cation transporterInhibitor0.5702
CYP450 2C9 substrateNon-substrate0.7975
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6906
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8236
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8626
Ames testNon AMES toxic0.8258
CarcinogenicityNon-carcinogens0.8873
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.9764 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.996
hERG inhibition (predictor II)Inhibitor0.6168
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0005-2920000000-e596d22799910844ad71

Taxonomy

Description
This compound belongs to the class of organic compounds known as pheniramines. These are compounds containing a pheniramine moiety, which is structurally characterized by the presence of a 2-benzylpyridine linked to an dimethyl(propyl)amine to form a dimethyl[3-phenyl-3-(pyridin-2-yl)propyl]amine skeleton.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Pheniramines
Direct Parent
Pheniramines
Alternative Parents
Aralkylamines / Benzene and substituted derivatives / Heteroaromatic compounds / Trialkylamines / Carboximidic acids / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Hydrocarbon derivatives
Substituents
Pheniramine / Aralkylamine / Monocyclic benzene moiety / Benzenoid / Heteroaromatic compound / Tertiary amine / Tertiary aliphatic amine / Carboximidic acid derivative / Carboximidic acid / Azacycle
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
tertiary amino compound, monocarboxylic acid amide, pyridines (CHEBI:4657)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the pr...
Gene Name
SCN5A
Uniprot ID
Q14524
Uniprot Name
Sodium channel protein type 5 subunit alpha
Molecular Weight
226937.475 Da
References
  1. Sugao M, Fujiki A, Nishida K, Sakabe M, Tsuneda T, Iwamoto J, Mizumaki K, Inoue H: Repolarization dynamics in patients with idiopathic ventricular fibrillation: pharmacological therapy with bepridil and disopyramide. J Cardiovasc Pharmacol. 2005 Jun;45(6):545-9. [PubMed:15897781]
  2. Fujiki A, Sugao M, Nishida K, Sakabe M, Tsuneda T, Mizumaki K, Inoue H: Repolarization abnormality in idiopathic ventricular fibrillation: assessment using 24-hour QT-RR and QaT-RR relationships. J Cardiovasc Electrophysiol. 2004 Jan;15(1):59-63. [PubMed:15028073]
  3. Shimizu W, Antzelevitch C, Suyama K, Kurita T, Taguchi A, Aihara N, Takaki H, Sunagawa K, Kamakura S: Effect of sodium channel blockers on ST segment, QRS duration, and corrected QT interval in patients with Brugada syndrome. J Cardiovasc Electrophysiol. 2000 Dec;11(12):1320-9. [PubMed:11196553]
  4. 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
Unknown
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. Yamamoto N, Ozaki T, Keida Y, Ohtsuka M, Goto T: A comparison of the binding characteristics of class I antiarrhythmic agents for human muscarinic m1-m3 receptors. J Cardiovasc Pharmacol. 1999 Jul;34(1):53-9. [PubMed:10413067]
  2. Ishida Y, Mizukami M, Taniguchi T, Satake N, Fujiwara M, Shibata S: Anticholinergic action of disopyramide in intestinal smooth muscle of the guinea pig: inhibition of muscarinic receptors (M1 and M2). Jpn J Pharmacol. 1990 Feb;52(2):363-70. [PubMed:1690310]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
G-protein coupled acetylcholine receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM2
Uniprot ID
P08172
Uniprot Name
Muscarinic acetylcholine receptor M2
Molecular Weight
51714.605 Da
References
  1. Yamamoto N, Ozaki T, Keida Y, Ohtsuka M, Goto T: A comparison of the binding characteristics of class I antiarrhythmic agents for human muscarinic m1-m3 receptors. J Cardiovasc Pharmacol. 1999 Jul;34(1):53-9. [PubMed:10413067]
  2. Ishida Y, Mizukami M, Taniguchi T, Satake N, Fujiwara M, Shibata S: Anticholinergic action of disopyramide in intestinal smooth muscle of the guinea pig: inhibition of muscarinic receptors (M1 and M2). Jpn J Pharmacol. 1990 Feb;52(2):363-70. [PubMed:1690310]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM3
Uniprot ID
P20309
Uniprot Name
Muscarinic acetylcholine receptor M3
Molecular Weight
66127.445 Da
References
  1. Yamamoto N, Ozaki T, Keida Y, Ohtsuka M, Goto T: A comparison of the binding characteristics of class I antiarrhythmic agents for human muscarinic m1-m3 receptors. J Cardiovasc Pharmacol. 1999 Jul;34(1):53-9. [PubMed:10413067]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity
Specific Function
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Mediates the major part of the dendritic A-type current I(SA) in brai...
Gene Name
KCND2
Uniprot ID
Q9NZV8
Uniprot Name
Potassium voltage-gated channel subfamily D member 2
Molecular Weight
70535.825 Da
References
  1. Casis O, Sanchez-Chapula JA: Disopyramide, imipramine, and amitriptyline bind to a common site on the transient outward K+ channel. J Cardiovasc Pharmacol. 1998 Oct;32(4):521-6. [PubMed:9781919]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Metal ion binding
Specific Function
Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated...
Gene Name
KCND3
Uniprot ID
Q9UK17
Uniprot Name
Potassium voltage-gated channel subfamily D member 3
Molecular Weight
73450.53 Da
References
  1. Casis O, Sanchez-Chapula JA: Disopyramide, imipramine, and amitriptyline bind to a common site on the transient outward K+ channel. J Cardiovasc Pharmacol. 1998 Oct;32(4):521-6. [PubMed:9781919]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...
Gene Name
KCNH2
Uniprot ID
Q12809
Uniprot Name
Potassium voltage-gated channel subfamily H member 2
Molecular Weight
126653.52 Da
References
  1. Chiu PJ, Marcoe KF, Bounds SE, Lin CH, Feng JJ, Lin A, Cheng FC, Crumb WJ, Mitchell R: Validation of a [3H]astemizole binding assay in HEK293 cells expressing HERG K+ channels. J Pharmacol Sci. 2004 Jul;95(3):311-9. [PubMed:15272206]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various hydrophobic ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and ava...
Gene Name
ORM2
Uniprot ID
P19652
Uniprot Name
Alpha-1-acid glycoprotein 2
Molecular Weight
23602.43 Da
References
  1. Herve F, Duche JC, d'Athis P, Marche C, Barre J, Tillement JP: Binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main genetic variants of human alpha 1-acid glycoprotein: evidence for drug-binding differences between the variants and for the presence of two separate drug-binding sites on alpha 1-acid glycoprotein. Pharmacogenetics. 1996 Oct;6(5):403-15. [PubMed:8946472]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Echizen H, Tanizaki M, Tatsuno J, Chiba K, Berwick T, Tani M, Gonzalez FJ, Ishizaki T: Identification of CYP3A4 as the enzyme involved in the mono-N-dealkylation of disopyramide enantiomers in humans. Drug Metab Dispos. 2000 Aug;28(8):937-44. [PubMed:10901704]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Zhang L, Fitzloff JF, Engel LC, Cook CS: Species difference in stereoselective involvement of CYP3A in the mono-N-dealkylation of disopyramide. Xenobiotica. 2001 Feb;31(2):73-83. [PubMed:11407536]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Zhang L, Fitzloff JF, Engel LC, Cook CS: Species difference in stereoselective involvement of CYP3A in the mono-N-dealkylation of disopyramide. Xenobiotica. 2001 Feb;31(2):73-83. [PubMed:11407536]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Other/unknown
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. Chu JS, Kishion S, Nomura A, Miyazaki K: Serum alpha 1-acid glycoprotein, sialic acid, and protein binding of disopyramide in normal subjects and cardiac patients. Zhongguo Yao Li Xue Bao. 1997 Sep;18(5):408-10. [PubMed:10322928]
  2. Hanada K, Ohta T, Hirai M, Arai M, Ogata H: Enantioselective binding of propranolol, disopyramide, and verapamil to human alpha(1)-acid glycoprotein. J Pharm Sci. 2000 Jun;89(6):751-7. [PubMed:10824133]
  3. Nakagawa T, Kishino S, Itoh S, Sugawara M, Miyazaki K: Differential binding of disopyramide and warfarin enantiomers to human alpha(1)-acid glycoprotein variants. Br J Clin Pharmacol. 2003 Dec;56(6):664-9. [PubMed:14616427]
  4. Haughey DB, Steinberg I, Lee MH: Protein binding of disopyramide--displacement by mono-N-dealkyldisopyramide and variation with source of alpha-1-acid glycoprotein. J Pharm Pharmacol. 1985 Apr;37(4):285-8. [PubMed:2860235]
  5. Brunner F, Muller WE: Prazosin binding to human alpha 1-acid glycoprotein (orosomucoid), human serum albumin, and human serum. Further characterization of the 'single drug binding site' of orosomucoid. J Pharm Pharmacol. 1985 May;37(5):305-9. [PubMed:2862237]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. Zhang L, Schaner ME, Giacomini KM: Functional characterization of an organic cation transporter (hOCT1) in a transiently transfected human cell line (HeLa). J Pharmacol Exp Ther. 1998 Jul;286(1):354-61. [PubMed:9655880]
  2. Urakami Y, Okuda M, Masuda S, Akazawa M, Saito H, Inui K: Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules. Pharm Res. 2001 Nov;18(11):1528-34. [PubMed:11758759]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. Urakami Y, Okuda M, Masuda S, Akazawa M, Saito H, Inui K: Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules. Pharm Res. 2001 Nov;18(11):1528-34. [PubMed:11758759]

Drug created on June 13, 2005 07:24 / Updated on November 20, 2018 13:19