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Identification
NameDisopyramide
Accession NumberDB00280  (APRD00507)
TypeSmall Molecule
GroupsApproved
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. [PubChem]

Structure
Thumb
Synonyms
Disopiramida
Disopyramidum
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Norpacecapsule, gelatin coated100 mg/1oralG.D. Searle LLC Division of Pfizer Inc1982-07-20Not applicableUs
Norpacecapsule, gelatin coated150 mg/1oralCarilion Materials Management1982-07-20Not applicableUs
Norpacecapsule, gelatin coated100 mg/1oralCarilion Materials Management1982-07-20Not applicableUs
Norpacecapsule, gelatin coated150 mg/1oralG.D. Searle LLC Division of Pfizer Inc1977-09-01Not applicableUs
Norpacecapsule, gelatin coated100 mg/1oralG.D. Searle LLC Division of Pfizer Inc1977-09-01Not applicableUs
Norpacecapsule, gelatin coated150 mg/1oralG.D. Searle LLC Division of Pfizer Inc1982-07-20Not applicableUs
Norpace Cap 100mgcapsule100 mgoralRoberts Pharmaceutical Canada Inc.1994-12-311999-08-11Canada
Norpace Cap 150mgcapsule150 mgoralRoberts Pharmaceutical Canada Inc.1994-12-311999-08-11Canada
Norpace CR 150mgtablet (extended-release)150 mgoralShire Biochem Inc1994-12-312004-04-30Canada
Rythmodancapsule150 mgoralSanofi Aventis Canada Inc2003-09-152012-05-24Canada
Rythmodancapsule100 mgoralSanofi Aventis Canada Inc2003-09-12Not applicableCanada
Rythmodan Cap 100mgcapsule100 mgoralRoussel Canada Inc.1977-12-311999-08-11Canada
Rythmodan Cap 150mgcapsule150 mgoralRoussel Canada Inc.1978-12-312000-07-28Canada
Rythmodan Capsules 100mgcapsule100 mgoralHoechst Roussel Canada Inc.1997-03-032007-07-31Canada
Rythmodan Capsules 150mgcapsule150 mgoralHoechst Roussel Canada Inc.1996-05-312005-08-01Canada
Rythmodan LA Tab 250mgtablet (extended-release)250 mgoralRoussel Canada Inc.1984-12-311997-08-05Canada
Rythmodan-LAtablet (extended-release)250 mgoralSanofi Aventis Canada Inc1999-04-302009-10-29Canada
Rythmodan-LA 250mgtablet (extended-release)250 mgoralHoechst Roussel Canada Inc.1995-12-312001-07-20Canada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Disopyramide Phosphatecapsule100 mg/1oralTeva Pharmaceuticals USA Inc1990-09-30Not applicableUs
Disopyramide Phosphatecapsule150 mg/1oralCarilion Materials Management1990-09-30Not applicableUs
Disopyramide Phosphatecapsule150 mg/1oralAv Kare, Inc.2014-01-03Not applicableUs
Disopyramide Phosphatecapsule100 mg/1oralAv Kare, Inc.2014-01-03Not applicableUs
Disopyramide Phosphatecapsule150 mg/1oralActavis Pharma, Inc.1985-05-31Not applicableUs
Disopyramide Phosphatecapsule100 mg/1oralActavis Pharma, Inc.1985-05-31Not applicableUs
Disopyramide Phosphatecapsule150 mg/1oralTeva Pharmaceuticals USA Inc1990-09-30Not applicableUs
Disopyramide Phosphatecapsule100 mg/1oralCarilion Materials Management1990-09-30Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
DicorantilSanofi
IsorythmSERP
LispineSawai Seiyaku
RitmodanSanofi
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Disopyramide phosphate
ThumbNot applicableDBSALT000899
Categories
UNIIGFO928U8MQ
CAS number3737-09-5
WeightAverage: 339.4745
Monoisotopic: 339.231062565
Chemical FormulaC21H29N3O
InChI KeyInChIKey=UVTNFZQICZKOEM-UHFFFAOYNA-N
InChI
InChI=1/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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyridines and derivatives
Sub ClassPheniramines
Direct ParentPheniramines
Alternative Parents
Substituents
  • Pheniramine
  • Phenylacetamide
  • Phenylpropylamine
  • Aralkylamine
  • Fatty acyl
  • Benzenoid
  • Fatty amide
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Tertiary aliphatic amine
  • Tertiary amine
  • Primary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, ventricular pre-excitation and cardiac dysrhythmias. It is a Class Ia antiarrhythmic drug.
PharmacodynamicsDisopyramide 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 actionDisopyramide 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.
Related Articles
AbsorptionNearly complete
Volume of distributionNot Available
Protein binding50%-65%
Metabolism

Hepatic

SubstrateEnzymesProduct
Disopyramide
mono-isopropyl-disopyramideDetails
Route of eliminationIn 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 life6.7 hours (range 4-10 hours)
ClearanceNot Available
ToxicityLD50=580 mg/kg in rats
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Disopyramide Action PathwayDrug actionSMP00325
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
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
Dosage forms
FormRouteStrength
Capsuleoral100 mg/1
Capsuleoral150 mg/1
Capsule, gelatin coatedoral100 mg/1
Capsule, gelatin coatedoral150 mg/1
Capsuleoral150 mg
Tablet (extended-release)oral150 mg
Capsuleoral100 mg
Tablet (extended-release)oral250 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.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point94.5-95 °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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
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 ReferencesNot Available
External Links
ATC CodesC01BA03
AHFS Codes
  • 24:04.04.04
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcebutololDisopyramide may increase the bradycardic activities of Acebutolol.
AcetohexamideAcetohexamide may increase the hypoglycemic activities of Disopyramide.
Acetylsalicylic acidAcetylsalicylic acid may increase the hypoglycemic activities of Disopyramide.
AclidiniumAclidinium may increase the anticholinergic activities of Disopyramide.
AlogliptinAlogliptin may increase the hypoglycemic activities of Disopyramide.
AmiodaroneAmiodarone may increase the QTc-prolonging activities of Disopyramide.
AprepitantThe serum concentration of Disopyramide can be increased when it is combined with Aprepitant.
AtenololDisopyramide may increase the bradycardic activities of Atenolol.
BetaxololDisopyramide may increase the bradycardic activities of Betaxolol.
BexaroteneThe serum concentration of Disopyramide can be decreased when it is combined with Bexarotene.
BisoprololDisopyramide may increase the bradycardic activities of Bisoprolol.
BosentanThe serum concentration of Disopyramide can be decreased when it is combined with Bosentan.
Botulinum Toxin Type ADisopyramide may increase the anticholinergic activities of Botulinum Toxin Type A.
Botulinum Toxin Type BDisopyramide may increase the anticholinergic activities of Botulinum Toxin Type B.
CanagliflozinCanagliflozin may increase the hypoglycemic activities of Disopyramide.
CarteololDisopyramide may increase the bradycardic activities of Carteolol.
CarvedilolDisopyramide may increase the bradycardic activities of Carvedilol.
ChlorpropamideChlorpropamide may increase the hypoglycemic activities of Disopyramide.
Cimetropium BromideDisopyramide may increase the anticholinergic activities of Cimetropium Bromide.
CitalopramCitalopram may increase the QTc-prolonging activities of Disopyramide.
ClarithromycinClarithromycin may increase the QTc-prolonging activities of Disopyramide.
ConivaptanThe serum concentration of Disopyramide can be increased when it is combined with Conivaptan.
DabrafenibThe serum concentration of Disopyramide can be decreased when it is combined with Dabrafenib.
DeferasiroxThe serum concentration of Disopyramide can be decreased when it is combined with Deferasirox.
DihydrotestosteroneDihydrotestosterone may increase the hypoglycemic activities of Disopyramide.
DofetilideDofetilide may increase the QTc-prolonging activities of Disopyramide.
DronabinolDisopyramide may increase the tachycardic activities of Dronabinol.
EluxadolineDisopyramide may increase the activities of Eluxadoline.
ErythromycinErythromycin may increase the QTc-prolonging activities of Disopyramide.
EsmololDisopyramide may increase the bradycardic activities of Esmolol.
EtravirineThe serum concentration of Disopyramide can be decreased when it is combined with Etravirine.
FingolimodFingolimod may increase the arrhythmogenic activities of Disopyramide.
FluconazoleThe metabolism of Disopyramide can be decreased when combined with Fluconazole.
FosaprepitantThe serum concentration of Disopyramide can be increased when it is combined with Fosaprepitant.
FosphenytoinDisopyramide may increase the QTc-prolonging activities of Fosphenytoin.
Fusidic AcidThe serum concentration of Disopyramide can be increased when it is combined with Fusidic Acid.
GliclazideGliclazide may increase the hypoglycemic activities of Disopyramide.
GlimepirideGlimepiride may increase the hypoglycemic activities of Disopyramide.
GliquidoneGliquidone may increase the hypoglycemic activities of Disopyramide.
Glucagon recombinantThe risk or severity of adverse effects can be increased when Disopyramide is combined with Glucagon recombinant.
GlyburideGlyburide may increase the hypoglycemic activities of Disopyramide.
GoserelinGoserelin may increase the QTc-prolonging activities of Disopyramide.
IdelalisibThe serum concentration of Disopyramide can be increased when it is combined with Idelalisib.
Insulin AspartInsulin Aspart may increase the hypoglycemic activities of Disopyramide.
Insulin DetemirInsulin Detemir may increase the hypoglycemic activities of Disopyramide.
Insulin GlargineInsulin Glargine may increase the hypoglycemic activities of Disopyramide.
Insulin GlulisineInsulin Glulisine may increase the hypoglycemic activities of Disopyramide.
Insulin HumanInsulin Regular may increase the hypoglycemic activities of Disopyramide.
Insulin LisproInsulin Lispro may increase the hypoglycemic activities of Disopyramide.
Ipratropium bromideIpratropium bromide may increase the anticholinergic activities of Disopyramide.
ItoprideThe therapeutic efficacy of Itopride can be decreased when used in combination with Disopyramide.
ItraconazoleThe serum concentration of Disopyramide can be increased when it is combined with Itraconazole.
IvabradineIvabradine may increase the QTc-prolonging activities of Disopyramide.
IvacaftorThe serum concentration of Disopyramide can be increased when it is combined with Ivacaftor.
KetoconazoleThe serum concentration of Disopyramide can be increased when it is combined with Ketoconazole.
LabetalolDisopyramide may increase the bradycardic activities of Labetalol.
LeuprolideLeuprolide may increase the QTc-prolonging activities of Disopyramide.
LidocaineDisopyramide may increase the arrhythmogenic activities of Lidocaine.
LinagliptinLinagliptin may increase the hypoglycemic activities of Disopyramide.
LuliconazoleThe serum concentration of Disopyramide can be increased when it is combined with Luliconazole.
LurasidoneLurasidone may increase the QTc-prolonging activities of Disopyramide.
MetforminMetformin may increase the hypoglycemic activities of Disopyramide.
MetoprololDisopyramide may increase the bradycardic activities of Metoprolol.
MifepristoneMifepristone may increase the QTc-prolonging activities of Disopyramide.
MitotaneThe serum concentration of Disopyramide can be decreased when it is combined with Mitotane.
MorphineThe risk or severity of adverse effects can be increased when Disopyramide is combined with Morphine.
NadololDisopyramide may increase the bradycardic activities of Nadolol.
NebivololDisopyramide may increase the bradycardic activities of Nebivolol.
NelfinavirThe metabolism of Disopyramide can be decreased when combined with Nelfinavir.
NetupitantThe serum concentration of Disopyramide can be increased when it is combined with Netupitant.
OctreotideOctreotide may increase the QTc-prolonging activities of Disopyramide.
OxandroloneOxandrolone may increase the hypoglycemic activities of Disopyramide.
PalbociclibThe serum concentration of Disopyramide can be increased when it is combined with Palbociclib.
ParoxetineParoxetine may increase the hypoglycemic activities of Disopyramide.
PegvisomantPegvisomant may increase the hypoglycemic activities of Disopyramide.
PenbutololDisopyramide may increase the bradycardic activities of Penbutolol.
PhenelzinePhenelzine may increase the hypoglycemic activities of Disopyramide.
PhenobarbitalThe serum concentration of Disopyramide can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Disopyramide can be decreased when it is combined with Phenytoin.
PindololDisopyramide may increase the bradycardic activities of Pindolol.
Potassium ChlorideDisopyramide may increase the ulcerogenic activities of Potassium Chloride.
PramlintidePramlintide may increase the anticholinergic activities of Disopyramide.
ProcyclidineThe risk or severity of adverse effects can be increased when Procyclidine is combined with Disopyramide.
PropafenonePropafenone may increase the arrhythmogenic activities of Disopyramide.
PropranololDisopyramide may increase the bradycardic activities of Propranolol.
RamosetronDisopyramide may increase the activities of Ramosetron.
RepaglinideRepaglinide may increase the hypoglycemic activities of Disopyramide.
RifampicinThe serum concentration of Disopyramide can be decreased when it is combined with Rifampicin.
SaxagliptinSaxagliptin may increase the hypoglycemic activities of Disopyramide.
SecretinThe therapeutic efficacy of Secretin can be decreased when used in combination with Disopyramide.
SiltuximabThe serum concentration of Disopyramide can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Disopyramide can be increased when it is combined with Simeprevir.
SparfloxacinSparfloxacin may increase the hypoglycemic activities of Disopyramide.
St. John's WortThe serum concentration of Disopyramide can be decreased when it is combined with St. John's Wort.
StiripentolThe serum concentration of Disopyramide can be increased when it is combined with Stiripentol.
SulpirideThe therapeutic efficacy of Sulpiride can be decreased when used in combination with Disopyramide.
TacrineThe therapeutic efficacy of Disopyramide can be decreased when used in combination with Tacrine.
TelithromycinTelithromycin may increase the QTc-prolonging activities of Disopyramide.
TestosteroneTestosterone may increase the hypoglycemic activities of Disopyramide.
TimololDisopyramide may increase the bradycardic activities of Timolol.
TiotropiumDisopyramide may increase the anticholinergic activities of Tiotropium.
TocilizumabThe serum concentration of Disopyramide can be decreased when it is combined with Tocilizumab.
TolbutamideTolbutamide may increase the hypoglycemic activities of Disopyramide.
TopiramateThe risk or severity of adverse effects can be increased when Disopyramide is combined with Topiramate.
TranylcypromineTranylcypromine may increase the hypoglycemic activities of Disopyramide.
TrichlormethiazideThe serum concentration of Trichlormethiazide can be increased when it is combined with Disopyramide.
UmeclidiniumUmeclidinium may increase the anticholinergic activities of Disopyramide.
VerapamilThe risk or severity of adverse effects can be increased when Verapamil is combined with Disopyramide.
VildagliptinVildagliptin may increase the hypoglycemic activities of Disopyramide.
Food Interactions
  • Avoid alcohol.
  • Take without regard to meals.

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 protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is respon...
Gene Name:
SCN5A
Uniprot ID:
Q14524
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 action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM1
Uniprot ID:
P11229
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 action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then trigge...
Gene Name:
CHRM2
Uniprot ID:
P08172
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 action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM3
Uniprot ID:
P20309
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 brain neurons (By similarity). This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the firs...
Gene Name:
KCND2
Uniprot ID:
Q9NZV8
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 by interactions with other alpha subunits and with regulatory subunits.
Gene Name:
KCND3
Uniprot ID:
Q9UK17
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 ]

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
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 ]

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 the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction.
Gene Name:
ORM1
Uniprot ID:
P02763
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-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine...
Gene Name:
SLC22A1
Uniprot ID:
O15245
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, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridiniu...
Gene Name:
SLC22A2
Uniprot ID:
O15244
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 ]
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Drug created on June 13, 2005 07:24 / Updated on April 15, 2014 12:23