Identification

Name
Quinidine
Accession Number
DB00908  (APRD00136)
Type
Small Molecule
Groups
Approved, Investigational
Description

An optical isomer of quinine, extracted from the bark of the Cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potential, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission.

Structure
Thumb
Synonyms
  • (+)-quinidine
  • (8R,9S)-Quinidine
  • (R)-(6-Methoxyquinolin-4-yl)((3S,4R,7S)-3-vinylquinuclidin-7-yl)methanol
  • (S)-(6-Methoxy-quinolin-4-yl)-((2R,5R)-5-vinyl-1-aza-bicyclo[2.2.2]oct-2-yl)-methanol
  • (S)-(6-Methoxyquinolin-4-yl)((2R,5R)-5-vinylquinuclidin-2-yl)methanol
  • 6-methoxy-α-(5-vinyl-2-quinuclidinyl)-4-quinolinemethanol
  • beta-Quinine
  • Chinidin
  • Chinidinum
  • CIN-QUIN
  • Conchinin
  • Conquinine
  • Pitayine
  • Quinidina
  • α-(6-methoxy-4-quinolyl)-5-vinyl-2-quinuclidinemethanol
  • β-quinine
Product Ingredients
IngredientUNIICASInChI Key
Quinidine gluconateR6875N380F7054-25-3XHKUDCCTVQUHJQ-LCYSNFERSA-N
Quinidine hydrochlorideS4P5V5597B1668-99-1LBSFSRMTJJPTCW-VJAUXQICSA-N
Quinidine polygalacturonateH0C54E9D6827555-34-6Not applicable
Quinidine sulfateJ13S2394HE6591-63-5LOUPRKONTZGTKE-UYVJDWJCSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo Quinidine Tab 200mgTablet200 mgOralApotex Corporation1979-12-312010-01-19Canada
Cardioquin TabletsTablet275 mgOralPurdue Pharma1961-12-312000-07-17Canada
Quinate Tab 325mgTablet325 mgOralRougier Pharma Division Of Ratiopharm Inc1979-12-312003-09-22Canada
Quinidex Extentabs Srt 300mgTablet, extended release300 mgOralAyerst Laboratories1991-12-311996-09-10Canada
Quinidex Extentabs Srt 300mgTablet, extended release300 mgOralWyeth Ayerst Canada Inc.1994-12-312001-10-29Canada
Quinidine 200 TabTablet200 mgOralPro Doc Limitee1982-12-312003-07-31Canada
Quinidine GluconateSolution80 mg/1mLIntravenousEli Lilly & Co. Ltd.1950-07-12Not applicableUs
Quinidine Gluconate for Inj 80mg/ml USPLiquid80 mgIntramuscular; IntravenousEli Lilly & Co. Ltd.1991-12-311997-08-13Canada
Quinidine Sulfate 200mgTablet200 mgOralRougier Pharma Division Of Ratiopharm Inc1970-12-311999-09-27Canada
Quinidine Sulfate Injection 190mg/mlSolution190 mgIntramuscularHospira, Inc.1981-12-31Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-quin-G Tab 325mgTablet325 mgOralApotex Corporation1985-12-312010-01-19Canada
Novo-quinidin 200mgTablet200 mgOralNovopharm Limited1966-12-312005-08-10Canada
Quinidine GluconateTablet, extended release324 mg/1OralSun Pharmaceutical Industries Limited1987-02-10Not applicableUs
Quinidine GluconateTablet, extended release324 mg/1OralPhysicians Total Care, Inc.1987-02-112012-06-30Us
Quinidine GluconateTablet, extended release324 mg/1OralRichmond Pharmaceuticals1987-02-10Not applicableUs
Quinidine GluconateTablet, extended release324 mg/1OralUDL Laboratories, Inc.2000-05-012014-10-31Us51079 02720180907 15195 1fmh780
Quinidine GluconateTablet, extended release324 mg/1OralCarilion Materials Management1987-02-10Not applicableUs53489 0141 05 nlmimage10 ba0e5d12
Quinidine SulfateTablet300 mg/1OralPhysicians Total Care, Inc.1983-09-262011-03-30Us
Quinidine SulfateTablet200 mg/1OralEon Labs, Inc.1976-11-24Not applicableUs
Quinidine SulfateTablet, film coated, extended release300 mg/1OralTeva1995-01-012016-03-31Us00093 9175 01 nlmimage10 b9355cea
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
NuedextaQuinidine sulfate (10 mg/1) + Dextromethorphan hydrobromide monohydrate (20 mg/1)Capsule, gelatin coatedOralAvanir Pharmaceuticals2010-12-01Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Quinidine GluconateQuinidine gluconate (324 mg/1)Tablet, extended releaseOralWatson Pharmaceuticals2007-02-17Not applicableUs
Quinidine SulfateQuinidine sulfate (100 mg/1)TabletOralMutual Pharmaceutical Company, Inc.2007-01-192007-01-19Us
International/Other Brands
Cardioquin / Kinidin / Quin-Release / Quinaglute / Quinalan / Quinicardine / Quinidex
Categories
UNII
ITX08688JL
CAS number
56-54-2
Weight
Average: 324.4168
Monoisotopic: 324.183778022
Chemical Formula
C20H24N2O2
InChI Key
LOUPRKONTZGTKE-LHHVKLHASA-N
InChI
InChI=1S/C20H24N2O2/c1-3-13-12-22-9-7-14(13)10-19(22)20(23)16-6-8-21-18-5-4-15(24-2)11-17(16)18/h3-6,8,11,13-14,19-20,23H,1,7,9-10,12H2,2H3/t13-,14-,19+,20-/m0/s1
IUPAC Name
(S)-[(2R,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl](6-methoxyquinolin-4-yl)methanol
SMILES
[H][C@@]12CCN(C[C@@H]1C=C)[C@]([H])(C2)[C@@H](O)C1=C2C=C(OC)C=CC2=NC=C1

Pharmacology

Indication

For the treatment of ventricular pre-excitation and cardiac dysrhythmias

Associated Conditions
Pharmacodynamics

Quinidine, a hydantoin anticonvulsant, is used alone or with phenobarbital or other anticonvulsants to manage tonic-clonic seizures, psychomotor seizures, neuropathic pain syndromes including diabetic neuropathy, digitalis-induced cardiac arrhythmias, and cardiac arrhythmias associated with QT-interval prolongation.

Mechanism of action

Quinidine acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. The antiarrhythmic actions are mediated through effects on sodium channels in Purkinje fibers. Quinidine may also act on the slow inward calcium current (ICa), the rapid (IKr) and slow (IKs) components of the delayed potassium rectifier current, the inward potassium rectifier current (IKI), the ATP-sensitive potassium channel (IKATP) and Ito.

TargetActionsOrganism
ASodium channel protein type 5 subunit alpha
inhibitor
Human
UPotassium channel subfamily K member 1
inhibitor
Human
UPotassium channel subfamily K member 6
inhibitor
Human
UPotassium voltage-gated channel subfamily H member 2
inhibitor
Human
UAlpha-1A adrenergic receptor
antagonist
Human
UAlpha-1B adrenergic receptor
antagonist
Human
UAlpha-1D adrenergic receptor
antagonist
Human
Absorption
Not Available
Volume of distribution
  • 2 to 3 L/kg
  • 0.5 L/kg [congestive heart failure]
  • 3 to 5 L/kg [cirrhosis of the liver]
Protein binding

80-88%

Metabolism
Route of elimination

When the urine pH is less than 7, about 20% of administered quinidine appears unchanged in the urine, but this fraction drops to as little as 5% when the urine is more alkaline.

Half life

6-8 hours

Clearance
  • 3 – 5 mL/min/kg [adults]
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Quinidine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of Quinidine can be decreased when used in combination with 1,10-Phenanthroline.
2-mercaptobenzothiazoleThe serum concentration of Quinidine can be increased when it is combined with 2-mercaptobenzothiazole.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Quinidine.
AbirateroneThe serum concentration of Quinidine can be increased when it is combined with Abiraterone.
AcebutololAcebutolol may increase the orthostatic hypotensive activities of Quinidine.
AcenocoumarolQuinidine may increase the anticoagulant activities of Acenocoumarol.
AcepromazineAcepromazine may increase the antihypertensive activities of Quinidine.
AceprometazineThe serum concentration of Aceprometazine can be increased when it is combined with Quinidine.
AcetaminophenThe serum concentration of Quinidine can be increased when it is combined with Acetaminophen.
AcetazolamideAcetazolamide may decrease the excretion rate of Quinidine which could result in a higher serum level.
Food Interactions
  • Preferably take on an ampty stomach.

References

Synthesis Reference

Jean Paul REMON, Chris Vervaet, "QUININE AND QUINIDINE SALTS, METHODS FOR MAKING THEM, AND PHARMACEUTICAL FORMULATIONS COMPRISING THEM." U.S. Patent US20090239900, issued September 24, 2009.

US20090239900
General References
Not Available
External Links
Human Metabolome Database
HMDB0015044
KEGG Drug
D08458
KEGG Compound
C06527
PubChem Compound
441074
PubChem Substance
46505356
ChemSpider
389880
BindingDB
50121975
ChEBI
28593
ChEMBL
CHEMBL1294
Therapeutic Targets Database
DAP000515
PharmGKB
PA451209
IUPHAR
2342
Guide to Pharmacology
GtP Drug Page
HET
QDN
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Quinidine
ATC Codes
C01BA01 — QuinidineC01BA51 — Quinidine, combinations excl. psycholepticsC01BA71 — Quinidine, combinations with psycholeptics
AHFS Codes
  • 24:04.00 — Cardiac Drugs
  • 24:04.04.04 — Class IA Antiarrythmics
PDB Entries
4wnu
FDA label
Download (615 KB)
MSDS
Download (73 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers2
1CompletedBasic ScienceDrug Induced Constipation1
1CompletedBasic ScienceHealthy Adult Male and Female Volunteers1
1CompletedTreatmentDrug-induced Surface ECG Changes1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentMajor Depressive Disorder (MDD)1
1RecruitingBasic ScienceNASH - Nonalcoholic Steatohepatitis1
1TerminatedTreatmentHealthy Volunteers1
2CompletedTreatmentAcute Agitation / Alzheimer's Disease (AD)1
2CompletedTreatmentAmyotrophic Lateral Sclerosis (ALS)1
2CompletedTreatmentAutism, Early Infantile1
2CompletedTreatmentCentral Neuropathic Pain / Disseminated Sclerosis1
2CompletedTreatmentDyskinesias / Parkinson's Disease (PD)1
2CompletedTreatmentEpisodic Migraine1
2CompletedTreatmentMajor Depressive Disorder (MDD) / Treatment Resistant1
2, 3RecruitingPreventionArrythmias1
3CompletedPreventionArrythmias / Cardiovascular Disease (CVD) / Heart Arrest / Heart Diseases / Myocardial Infarction / Severe ventricular arrhythmias1
3CompletedTreatmentArrythmias / Cardiovascular Disease (CVD) / Death, Sudden,Cardiac / Heart Diseases / Severe ventricular arrhythmias / Ventricular Arrythmias / Ventricular Tachycardia (VT)1
3CompletedTreatmentArrythmias / Cardiovascular Disease (CVD) / Heart Diseases / Nonvalvular Atrial Fibrillation1
3CompletedTreatmentPseudobulbar Affect (PBA)1
4Active Not RecruitingSupportive CareAlzheimer's Disease (AD) / Pseudobulbar Affect (PBA)1
4TerminatedNot AvailablePseudobulbar Affect (Involuntary Laughing and/or Crying)1
4Unknown StatusTreatmentDementias / Pseudobulbar Affect (PBA) / Strokes / Traumatic Brain Injury (TBI)1

Pharmacoeconomics

Manufacturers
  • Eli lilly and co
  • Warner chilcott div warner lambert co
  • Bayer healthcare pharmaceuticals inc
  • Lannett co inc
  • Watson laboratories inc
  • Ascot hosp pharmaceuticals inc div travenol laboratories inc
  • Halsey drug co inc
  • Mutual pharmaceutical co inc
  • Roxane laboratories inc
  • Sandoz inc
  • Superpharm corp
  • Pharmaceutical research assoc inc
  • Solvay pharmaceuticals
  • Wyeth pharmaceuticals inc
  • Teva pharmaceuticals usa
  • Barr laboratories inc
  • Clonmel healthcare ltd
  • Contract pharmacal corp
  • Elkins sinn div ah robins co inc
  • Everylife
  • Impax laboratories inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • King pharmaceuticals inc
  • Kv pharmaceutical co
  • Lederle laboratories div american cyanamid co
  • L perrigo co
  • Pharmavite pharmaceuticals
  • Purepac pharmaceutical co
  • Scherer laboratories inc
  • Usl pharma inc
  • Valeant pharmaceuticals international
  • Vangard laboratories inc div midway medical co
  • Vintage pharmaceuticals inc
  • West ward pharmaceutical corp
  • Whiteworth towne paulsen inc
  • Key pharmaceuticals inc sub schering plough corp
  • Schering corp
Packagers
  • Amend
  • Amerisource Health Services Corp.
  • Apotheca Inc.
  • Consolidated Midland Corp.
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Eli Lilly & Co.
  • Eon Labs
  • H and H Laboratories
  • Heartland Repack Services LLC
  • Kaiser Foundation Hospital
  • Major Pharmaceuticals
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • PD-Rx Pharmaceuticals Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Qualitest
  • Resource Optimization and Innovation LLC
  • Richmond Pharmacy
  • Sandhills Packaging Inc.
  • Southwood Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
  • UDL Laboratories
  • Watson Pharmaceuticals
Dosage forms
FormRouteStrength
TabletOral275 mg
Capsule, gelatin coatedOral
TabletOral325 mg
Tablet, extended releaseOral300 mg
SolutionIntravenous80 mg/1mL
Tablet, extended releaseOral324 mg/1
LiquidIntramuscular; Intravenous80 mg
TabletOral100 mg/1
TabletOral200 mg/1
TabletOral300 mg/1
Tablet, film coated, extended releaseOral300 mg/1
SolutionIntramuscular190 mg
TabletOral195 mg
TabletOral200 mg
Prices
Unit descriptionCostUnit
Quinidine gluc 80 mg/ml vial2.16USD ml
Quinidine sulfate crystals1.58USD g
QuiNIDine Gluconate CR 324 mg Controlled Release Tabs0.97USD tab
Quinidine gluc er 324 mg tab0.93USD each
Quinidine Sulfate 300 mg0.41USD tablet
Quinidine sulfate 300 mg tablet0.4USD tablet
Quinidine Sulfate 200 mg0.22USD tablet
Quinidine sulfate 200 mg tablet0.21USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7659282No2006-08-132026-08-13Us
US8227484No2003-07-172023-07-17Us
USRE38115No1996-01-262016-01-26Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)174 °CPhysProp
water solubility140 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP3.44HANSCH,C ET AL. (1995)
logS-3.37ADME Research, USCD
Caco2 permeability-4.69ADME Research, USCD
pKa8.56 (at 25 °C)SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.334 mg/mLALOGPS
logP2.82ALOGPS
logP2.51ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)13.89ChemAxon
pKa (Strongest Basic)9.05ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area45.59 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity94.69 m3·mol-1ChemAxon
Polarizability35.82 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9836
Blood Brain Barrier+0.9382
Caco-2 permeable+0.8867
P-glycoprotein substrateSubstrate0.7863
P-glycoprotein inhibitor IInhibitor0.8208
P-glycoprotein inhibitor IIInhibitor0.8387
Renal organic cation transporterInhibitor0.762
CYP450 2C9 substrateNon-substrate0.7898
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.5754
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7225
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.972
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.0596 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.5884
hERG inhibition (predictor II)Inhibitor0.538
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (2.96 KB)
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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-0bt9-0908000000-f7ff24907014d8850472
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-08fr-0907000000-f6d31042d549da6bcfd0
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-0bt9-0709000000-2c0e665e2c3031c8e517
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-00di-0009133000-a893d9e0e441c597fac3
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-00di-0009001000-0a0220fd8eeb9e62bc20
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-0a4i-0469000000-3679f13f09481b3563c8
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-0a4i-0459000000-60c4a39356a4afeef2d2
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-0a4i-0239000000-644b48bb63dd87dac231
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03di-0910000000-b0045fccdbe90e598912
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-0229000000-f88b510f13aab6a2bb44
MS/MS Spectrum - , positiveLC-MS/MSsplash10-02ta-3900000000-46a157d2899290cbf4ab
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0200-2952000000-2777ab3374ec2b052b2e

Taxonomy

Description
This compound belongs to the class of organic compounds known as cinchona alkaloids. These are alkaloids structurally characterized by the presence of the cinchonan skeleton, which consists of a quinoline linked to an azabicyclo[2.2.2]octane moiety.
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Cinchona alkaloids
Sub Class
Not Available
Direct Parent
Cinchona alkaloids
Alternative Parents
4-quinolinemethanols / Quinuclidines / Anisoles / Aralkylamines / Alkyl aryl ethers / Pyridines and derivatives / Piperidines / Heteroaromatic compounds / Trialkylamines / Secondary alcohols
show 5 more
Substituents
Cinchonan-skeleton / 4-quinolinemethanol / Quinoline / Anisole / Quinuclidine / Alkyl aryl ether / Aralkylamine / Piperidine / Pyridine / Benzenoid
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
cinchona alkaloid (CHEBI:28593)

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. Stokoe KS, Thomas G, Goddard CA, Colledge WH, Grace AA, Huang CL: Effects of flecainide and quinidine on arrhythmogenic properties of Scn5a+/Delta murine hearts modelling long QT syndrome 3. J Physiol. 2007 Jan 1;578(Pt 1):69-84. Epub 2006 Oct 5. [PubMed:17023504]
  2. Itoh H, Shimizu M, Takata S, Mabuchi H, Imoto K: A novel missense mutation in the SCN5A gene associated with Brugada syndrome bidirectionally affecting blocking actions of antiarrhythmic drugs. J Cardiovasc Electrophysiol. 2005 May;16(5):486-93. [PubMed:15877619]
  3. Grant AO: Electrophysiological basis and genetics of Brugada syndrome. J Cardiovasc Electrophysiol. 2005 Sep;16 Suppl 1:S3-7. [PubMed:16138883]
  4. Napolitano C, Priori SG: Brugada syndrome. Orphanet J Rare Dis. 2006 Sep 14;1:35. [PubMed:16972995]
  5. Ohgo T, Okamura H, Noda T, Satomi K, Suyama K, Kurita T, Aihara N, Kamakura S, Ohe T, Shimizu W: Acute and chronic management in patients with Brugada syndrome associated with electrical storm of ventricular fibrillation. Heart Rhythm. 2007 Jun;4(6):695-700. Epub 2007 Feb 20. [PubMed:17556186]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  7. Sheets MF, Fozzard HA, Lipkind GM, Hanck DA: Sodium channel molecular conformations and antiarrhythmic drug affinity. Trends Cardiovasc Med. 2010 Jan;20(1):16-21. doi: 10.1016/j.tcm.2010.03.002. [PubMed:20685573]
  8. Tella SR, Goldberg SR: Monoamine transporter and sodium channel mechanisms in the rapid pressor response to cocaine. Pharmacol Biochem Behav. 1998 Feb;59(2):305-12. [PubMed:9476974]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium channel activity
Specific Function
Ion channel that contributes to passive transmembrane potassium transport and to the regulation of the resting membrane potential in brain astrocytes, but also in kidney and in other tissues (PubMe...
Gene Name
KCNK1
Uniprot ID
O00180
Uniprot Name
Potassium channel subfamily K member 1
Molecular Weight
38142.775 Da
References
  1. Lesage F, Guillemare E, Fink M, Duprat F, Lazdunski M, Romey G, Barhanin J: TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure. EMBO J. 1996 Mar 1;15(5):1004-11. [PubMed:8605869]
  2. Fink M, Duprat F, Lesage F, Reyes R, Romey G, Heurteaux C, Lazdunski M: Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel. EMBO J. 1996 Dec 16;15(24):6854-62. [PubMed:9003761]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Potassium ion leak channel activity
Specific Function
Exhibits outward rectification in a physiological K(+) gradient and mild inward rectification in symmetrical K(+) conditions.
Gene Name
KCNK6
Uniprot ID
Q9Y257
Uniprot Name
Potassium channel subfamily K member 6
Molecular Weight
33746.8 Da
References
  1. Patel AJ, Maingret F, Magnone V, Fosset M, Lazdunski M, Honore E: TWIK-2, an inactivating 2P domain K+ channel. J Biol Chem. 2000 Sep 15;275(37):28722-30. [PubMed:10887187]
  2. Guerard NC, Traebert M, Suter W, Dumotier BM: Selective block of IKs plays a significant role in MAP triangulation induced by IKr block in isolated rabbit heart. J Pharmacol Toxicol Methods. 2008 Jul-Aug;58(1):32-40. doi: 10.1016/j.vascn.2008.05.129. Epub 2008 Jun 8. [PubMed:18582585]
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. Po SS, Wang DW, Yang IC, Johnson JP Jr, Nie L, Bennett PB: Modulation of HERG potassium channels by extracellular magnesium and quinidine. J Cardiovasc Pharmacol. 1999 Feb;33(2):181-5. [PubMed:10028924]
  2. Dong DL, Li Z, Wang HZ, Du ZM, Song WH, Yang BF: Acidification alters antiarrhythmic drug blockade of the ether-a-go-go-related Gene (HERG) Channels. Basic Clin Pharmacol Toxicol. 2004 May;94(5):209-12. [PubMed:15125690]
  3. Wolpert C, Schimpf R, Giustetto C, Antzelevitch C, Cordeiro J, Dumaine R, Brugada R, Hong K, Bauersfeld U, Gaita F, Borggrefe M: Further insights into the effect of quinidine in short QT syndrome caused by a mutation in HERG. J Cardiovasc Electrophysiol. 2005 Jan;16(1):54-8. [PubMed:15673388]
  4. Lin C, Ke X, Cvetanovic I, Ranade V, Somberg J: The influence of extracellular acidosis on the effect of IKr blockers. J Cardiovasc Pharmacol Ther. 2005 Mar;10(1):67-76. [PubMed:15821840]
  5. Lin C, Cvetanovic I, Ke X, Ranade V, Somberg J: A mechanism for the potential proarrhythmic effect of acidosis, bradycardia, and hypokalemia on the blockade of human ether-a-go-go-related gene (HERG) channels. Am J Ther. 2005 Jul-Aug;12(4):328-36. [PubMed:16041196]
  6. Guerard NC, Traebert M, Suter W, Dumotier BM: Selective block of IKs plays a significant role in MAP triangulation induced by IKr block in isolated rabbit heart. J Pharmacol Toxicol Methods. 2008 Jul-Aug;58(1):32-40. doi: 10.1016/j.vascn.2008.05.129. Epub 2008 Jun 8. [PubMed:18582585]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Shibata K, Hirasawa A, Foglar R, Ogawa S, Tsujimoto G: Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors. Circulation. 1998 Apr 7;97(13):1227-30. [PubMed:9570190]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. Shibata K, Hirasawa A, Foglar R, Ogawa S, Tsujimoto G: Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors. Circulation. 1998 Apr 7;97(13):1227-30. [PubMed:9570190]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Alpha1-adrenergic receptor activity
Specific Function
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name
ADRA1D
Uniprot ID
P25100
Uniprot Name
Alpha-1D adrenergic receptor
Molecular Weight
60462.205 Da
References
  1. Shibata K, Hirasawa A, Foglar R, Ogawa S, Tsujimoto G: Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors. Circulation. 1998 Apr 7;97(13):1227-30. [PubMed:9570190]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
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. Ludwig E, Schmid J, Beschke K, Ebner T: Activation of human cytochrome P-450 3A4-catalyzed meloxicam 5'-methylhydroxylation by quinidine and hydroquinidine in vitro. J Pharmacol Exp Ther. 1999 Jul;290(1):1-8. [PubMed:10381752]
  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. Ekins S, Bravi G, Wikel JH, Wrighton SA: Three-dimensional-quantitative structure activity relationship analysis of cytochrome P-450 3A4 substrates. J Pharmacol Exp Ther. 1999 Oct;291(1):424-33. [PubMed:10490933]
  4. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
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
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Details
3. Cytochrome P450 2D6
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. 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]
  2. Berka K, Anzenbacherova E, Hendrychova T, Lange R, Masek V, Anzenbacher P, Otyepka M: Binding of quinidine radically increases the stability and decreases the flexibility of the cytochrome P450 2D6 active site. J Inorg Biochem. 2012 May;110:46-50. doi: 10.1016/j.jinorgbio.2012.02.010. Epub 2012 Feb 22. [PubMed:22459173]
  3. Hutzler JM, Walker GS, Wienkers LC: Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9. doi: 10.1021/tx025674x. [PubMed:12703961]
  4. von Moltke LL, Greenblatt DJ, Duan SX, Daily JP, Harmatz JS, Shader RI: Inhibition of desipramine hydroxylation (Cytochrome P450-2D6) in vitro by quinidine and by viral protease inhibitors: relation to drug interactions in vivo. J Pharm Sci. 1998 Oct;87(10):1184-9. doi: 10.1021/js980197h. [PubMed:9758674]
  5. Bramer SL, Suri A: Inhibition of CYP2D6 by quinidine and its effects on the metabolism of cilostazol. Clin Pharmacokinet. 1999;37 Suppl 2:41-51. [PubMed:10702886]
  6. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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. 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]
  2. Ching MS, Blake CL, Malek NA, Angus PW, Ghabrial H: Differential inhibition of human CYP1A1 and CYP1A2 by quinidine and quinine. Xenobiotica. 2001 Nov;31(11):757-67. doi: 10.1080/00498250110065603 . [PubMed:11765139]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. 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]
  2. Nielsen TL, Rasmussen BB, Flinois JP, Beaune P, Brosen K: In vitro metabolism of quinidine: the (3S)-3-hydroxylation of quinidine is a specific marker reaction for cytochrome P-4503A4 activity in human liver microsomes. J Pharmacol Exp Ther. 1999 Apr;289(1):31-7. [PubMed:10086984]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vitamin d 24-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 oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. 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]
  2. van Montfoort JE, Hagenbuch B, Fattinger KE, Muller M, Groothuis GM, Meijer DK, Meier PJ: Polyspecific organic anion transporting polypeptides mediate hepatic uptake of amphipathic type II organic cations. J Pharmacol Exp Ther. 1999 Oct;291(1):147-52. [PubMed:10490898]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. 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]
  2. Spracklin DK, Thummel KE, Kharasch ED: Human reductive halothane metabolism in vitro is catalyzed by cytochrome P450 2A6 and 3A4. Drug Metab Dispos. 1996 Sep;24(9):976-83. [PubMed:8886607]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. 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]
  2. Nielsen TL, Rasmussen BB, Flinois JP, Beaune P, Brosen K: In vitro metabolism of quinidine: the (3S)-3-hydroxylation of quinidine is a specific marker reaction for cytochrome P-4503A4 activity in human liver microsomes. J Pharmacol Exp Ther. 1999 Apr;289(1):31-7. [PubMed:10086984]
  3. Sai Y, Dai R, Yang TJ, Krausz KW, Gonzalez FJ, Gelboin HV, Shou M: Assessment of specificity of eight chemical inhibitors using cDNA-expressed cytochromes P450. Xenobiotica. 2000 Apr;30(4):327-43. [PubMed:10821163]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [PubMed:26721703]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
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. Li JH, Xu JQ, Cao XM, Ni L, Li Y, Zhuang YY, Gong JB: Influence of the ORM1 phenotypes on serum unbound concentration and protein binding of quinidine. Clin Chim Acta. 2002 Mar;317(1-2):85-92. [PubMed:11814462]
  2. McCollam PL, Crouch MA, Arnaud P: Caucasian versus African-American differences in orosomucoid: potential implications for therapy. Pharmacotherapy. 1998 May-Jun;18(3):620-6. [PubMed:9620113]

Transporters

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, Akazawa M, Saito H, Okuda M, Inui K: cDNA cloning, functional characterization, and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney. J Am Soc Nephrol. 2002 Jul;13(7):1703-10. [PubMed:12089365]
  2. Arndt P, Volk C, Gorboulev V, Budiman T, Popp C, Ulzheimer-Teuber I, Akhoundova A, Koppatz S, Bamberg E, Nagel G, Koepsell H: Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1. Am J Physiol Renal Physiol. 2001 Sep;281(3):F454-68. [PubMed:11502595]
  3. Urakami Y, Okuda M, Masuda S, Saito H, Inui KI: Functional characteristics and membrane localization of rat multispecific organic cation transporters, OCT1 and OCT2, mediating tubular secretion of cationic drugs. J Pharmacol Exp Ther. 1998 Nov;287(2):800-5. [PubMed:9808712]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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. van Montfoort JE, Muller M, Groothuis GM, Meijer DK, Koepsell H, Meier PJ: Comparison of "type I" and "type II" organic cation transport by organic cation transporters and organic anion-transporting polypeptides. J Pharmacol Exp Ther. 2001 Jul;298(1):110-5. [PubMed:11408531]
  2. Bednarczyk D, Ekins S, Wikel JH, Wright SH: Influence of molecular structure on substrate binding to the human organic cation transporter, hOCT1. Mol Pharmacol. 2003 Mar;63(3):489-98. [PubMed:12606755]
  3. Zhang L, Dresser MJ, Gray AT, Yost SC, Terashita S, Giacomini KM: Cloning and functional expression of a human liver organic cation transporter. Mol Pharmacol. 1997 Jun;51(6):913-21. [PubMed:9187257]
  4. 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]
  5. Zhang L, Gorset W, Dresser MJ, Giacomini KM: The interaction of n-tetraalkylammonium compounds with a human organic cation transporter, hOCT1. J Pharmacol Exp Ther. 1999 Mar;288(3):1192-8. [PubMed:10027858]
  6. Sandhu P, Lee W, Xu X, Leake BF, Yamazaki M, Stone JA, Lin JH, Pearson PG, Kim RB: Hepatic uptake of the novel antifungal agent caspofungin. Drug Metab Dispos. 2005 May;33(5):676-82. Epub 2005 Feb 16. [PubMed:15716364]
  7. Sinclair CJ, Chi KD, Subramanian V, Ward KL, Green RM: Functional expression of a high affinity mammalian hepatic choline/organic cation transporter. J Lipid Res. 2000 Nov;41(11):1841-8. [PubMed:11060354]
  8. Arndt P, Volk C, Gorboulev V, Budiman T, Popp C, Ulzheimer-Teuber I, Akhoundova A, Koppatz S, Bamberg E, Nagel G, Koepsell H: Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1. Am J Physiol Renal Physiol. 2001 Sep;281(3):F454-68. [PubMed:11502595]
  9. Urakami Y, Okuda M, Masuda S, Saito H, Inui KI: Functional characteristics and membrane localization of rat multispecific organic cation transporters, OCT1 and OCT2, mediating tubular secretion of cationic drugs. J Pharmacol Exp Ther. 1998 Nov;287(2):800-5. [PubMed:9808712]
  10. Martel F, Vetter T, Russ H, Grundemann D, Azevedo I, Koepsell H, Schomig E: Transport of small organic cations in the rat liver. The role of the organic cation transporter OCT1. Naunyn Schmiedebergs Arch Pharmacol. 1996 Aug-Sep;354(3):320-6. [PubMed:8878062]
  11. Busch AE, Quester S, Ulzheimer JC, Gorboulev V, Akhoundova A, Waldegger S, Lang F, Koepsell H: Monoamine neurotransmitter transport mediated by the polyspecific cation transporter rOCT1. FEBS Lett. 1996 Oct 21;395(2-3):153-6. [PubMed:8898084]
  12. Busch AE, Quester S, Ulzheimer JC, Waldegger S, Gorboulev V, Arndt P, Lang F, Koepsell H: Electrogenic properties and substrate specificity of the polyspecific rat cation transporter rOCT1. J Biol Chem. 1996 Dec 20;271(51):32599-604. [PubMed:8955087]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Symporter activity
Specific Function
Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cat...
Gene Name
SLC22A5
Uniprot ID
O76082
Uniprot Name
Solute carrier family 22 member 5
Molecular Weight
62751.08 Da
References
  1. Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. [PubMed:10525100]
  2. Ohashi R, Tamai I, Nezu Ji J, Nikaido H, Hashimoto N, Oku A, Sai Y, Shimane M, Tsuji A: Molecular and physiological evidence for multifunctionality of carnitine/organic cation transporter OCTN2. Mol Pharmacol. 2001 Feb;59(2):358-66. [PubMed:11160873]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Choo EF, Leake B, Wandel C, Imamura H, Wood AJ, Wilkinson GR, Kim RB: Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes. Drug Metab Dispos. 2000 Jun;28(6):655-60. [PubMed:10820137]
  2. Gao J, Murase O, Schowen RL, Aube J, Borchardt RT: A functional assay for quantitation of the apparent affinities of ligands of P-glycoprotein in Caco-2 cells. Pharm Res. 2001 Feb;18(2):171-6. [PubMed:11405287]
  3. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. [PubMed:11716514]
  4. Tang F, Horie K, Borchardt RT: Are MDCK cells transfected with the human MDR1 gene a good model of the human intestinal mucosa? Pharm Res. 2002 Jun;19(6):765-72. [PubMed:12134945]
  5. Horie K, Tang F, Borchardt RT: Isolation and characterization of Caco-2 subclones expressing high levels of multidrug resistance protein efflux transporter. Pharm Res. 2003 Feb;20(2):161-8. [PubMed:12636153]
  6. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [PubMed:12699389]
  7. Weiss J, Dormann SM, Martin-Facklam M, Kerpen CJ, Ketabi-Kiyanvash N, Haefeli WE: Inhibition of P-glycoprotein by newer antidepressants. J Pharmacol Exp Ther. 2003 Apr;305(1):197-204. [PubMed:12649369]
  8. Tanigawara Y, Okamura N, Hirai M, Yasuhara M, Ueda K, Kioka N, Komano T, Hori R: Transport of digoxin by human P-glycoprotein expressed in a porcine kidney epithelial cell line (LLC-PK1). J Pharmacol Exp Ther. 1992 Nov;263(2):840-5. [PubMed:1359120]
  9. Ito T, Yano I, Tanaka K, Inui KI: Transport of quinolone antibacterial drugs by human P-glycoprotein expressed in a kidney epithelial cell line, LLC-PK1. J Pharmacol Exp Ther. 1997 Aug;282(2):955-60. [PubMed:9262363]
  10. Kim RB, Fromm MF, Wandel C, Leake B, Wood AJ, Roden DM, Wilkinson GR: The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Invest. 1998 Jan 15;101(2):289-94. [PubMed:9435299]
  11. Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. [PubMed:14985103]
  12. Jutabha P, Wempe MF, Anzai N, Otomo J, Kadota T, Endou H: Xenopus laevis oocytes expressing human P-glycoprotein: probing trans- and cis-inhibitory effects on [3H]vinblastine and [3H]digoxin efflux. Pharmacol Res. 2010 Jan;61(1):76-84. doi: 10.1016/j.phrs.2009.07.002. Epub 2009 Jul 21. [PubMed:19631272]
  13. Dahan A, Amidon GL: Small intestinal efflux mediated by MRP2 and BCRP shifts sulfasalazine intestinal permeability from high to low, enabling its colonic targeting. Am J Physiol Gastrointest Liver Physiol. 2009 Aug;297(2):G371-7. doi: 10.1152/ajpgi.00102.2009. Epub 2009 Jun 18. [PubMed:19541926]
  14. Dahan A, Sabit H, Amidon GL: The H2 receptor antagonist nizatidine is a P-glycoprotein substrate: characterization of its intestinal epithelial cell efflux transport. AAPS J. 2009 Jun;11(2):205-13. doi: 10.1208/s12248-009-9092-5. Epub 2009 Mar 25. [PubMed:19319690]
  15. Smith BJ, Doran AC, McLean S, Tingley FD 3rd, O'Neill BT, Kajiji SM: P-glycoprotein efflux at the blood-brain barrier mediates differences in brain disposition and pharmacodynamics between two structurally related neurokinin-1 receptor antagonists. J Pharmacol Exp Ther. 2001 Sep;298(3):1252-9. [PubMed:11504828]
  16. Adachi Y, Suzuki H, Sugiyama Y: Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8. [PubMed:11785684]
  17. Neuhoff S, Ungell AL, Zamora I, Artursson P: pH-dependent bidirectional transport of weakly basic drugs across Caco-2 monolayers: implications for drug-drug interactions. Pharm Res. 2003 Aug;20(8):1141-8. [PubMed:12948010]
  18. Troutman MD, Thakker DR: Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res. 2003 Aug;20(8):1210-24. [PubMed:12948019]
  19. Faassen F, Vogel G, Spanings H, Vromans H: Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs. Int J Pharm. 2003 Sep 16;263(1-2):113-22. [PubMed:12954186]
  20. Fromm MF, Kim RB, Stein CM, Wilkinson GR, Roden DM: Inhibition of P-glycoprotein-mediated drug transport: A unifying mechanism to explain the interaction between digoxin and quinidine [seecomments]. Circulation. 1999 Feb 2;99(4):552-7. [PubMed:9927403]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. van Montfoort JE, Muller M, Groothuis GM, Meijer DK, Koepsell H, Meier PJ: Comparison of "type I" and "type II" organic cation transport by organic cation transporters and organic anion-transporting polypeptides. J Pharmacol Exp Ther. 2001 Jul;298(1):110-5. [PubMed:11408531]
  2. Cvetkovic M, Leake B, Fromm MF, Wilkinson GR, Kim RB: OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos. 1999 Aug;27(8):866-71. [PubMed:10421612]
  3. Shitara Y, Sugiyama D, Kusuhara H, Kato Y, Abe T, Meier PJ, Itoh T, Sugiyama Y: Comparative inhibitory effects of different compounds on rat oatpl (slc21a1)- and Oatp2 (Slc21a5)-mediated transport. Pharm Res. 2002 Feb;19(2):147-53. [PubMed:11883641]
  4. van Montfoort JE, Hagenbuch B, Fattinger KE, Muller M, Groothuis GM, Meijer DK, Meier PJ: Polyspecific organic anion transporting polypeptides mediate hepatic uptake of amphipathic type II organic cations. J Pharmacol Exp Ther. 1999 Oct;291(1):147-52. [PubMed:10490898]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H: Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86. [PubMed:11306713]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. Tang F, Horie K, Borchardt RT: Are MDCK cells transfected with the human MRP2 gene a good model of the human intestinal mucosa? Pharm Res. 2002 Jun;19(6):773-9. [PubMed:12134946]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Symporter activity
Specific Function
Sodium-ion dependent, low affinity carnitine transporter. Probably transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without...
Gene Name
SLC22A4
Uniprot ID
Q9H015
Uniprot Name
Solute carrier family 22 member 4
Molecular Weight
62154.48 Da
References
  1. Yabuuchi H, Tamai I, Nezu J, Sakamoto K, Oku A, Shimane M, Sai Y, Tsuji A: Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther. 1999 May;289(2):768-73. [PubMed:10215651]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Nozawa T, Tamai I, Sai Y, Nezu J, Tsuji A: Contribution of organic anion transporting polypeptide OATP-C to hepatic elimination of the opioid pentapeptide analogue [D-Ala2, D-Leu5]-enkephalin. J Pharm Pharmacol. 2003 Jul;55(7):1013-20. [PubMed:12906759]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Wilson A. (2016). New horizons in predictive drug metabolism and pharmacokinetics. The Royal Society of Chemistry. [ISBN:978-1-84973-828-6]

Drug created on June 13, 2005 07:24 / Updated on September 24, 2018 02:40