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Identification
Name Quinidine
Accession Number DB00908 (APRD00136)
Type small molecule
Groups approved
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. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Quinidine Gluconate
  • Quinidine Sulfate
Brand names
  • Apo-Quinidine
  • Biquin Durules
  • Cardioquin
  • Chinidin
  • Cin-Quin
  • Coccinine
  • Conchinin
  • Conchinine
  • Conquinine
  • Duraquin
  • Kinidin
  • Novoquinidin
  • Pitayin
  • Pitayine
  • Quin-Release
  • Quinact
  • Quinaglute
  • Quinaglute Dura-Tabs
  • Quinalan
  • Quinate
  • Quinatime
  • Quindine
  • Quinicardine
  • Quinidex
  • Quinidex Extentabs
  • Quinora
Brand name mixtures Not Available
Categories
  • Enzyme Inhibitors
  • Antiarrhythmic Agents
  • Antimalarials
  • Muscarinic Antagonists
  • Adrenergic alpha-Antagonists
  • Anti-Arrhythmia Agents
CAS number 56-54-2
Weight Average: 324.4168
Monoisotopic: 324.183778022
Chemical Formula C20H24N2O2
InChI Key InChIKey=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
Plain Text
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=CC=NC2=C1C=C(OC)C=C2
Plain Text
Mass Spec show (3 KB)
Taxonomy
Kingdom Organic
Classes
  • Alkaloids and Alkaloid Derivatives
Substructures
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Phenols and Derivatives
  • Pyridines and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Hydroxyquinolines
  • Aliphatic and Aryl Amines
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Alkaloids and Alkaloid Derivatives
  • (Iso)quinolines and Derivatives
  • Alcohols and Polyols
  • Phenyl Esters
  • Piperidines
Pharmacology
Indication For the treatment of ventricular pre-excitation and cardiac dysrhythmias
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.
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
Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 3A4 3-Hydroxyquinidine 3-hydroxylation 4 0
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
Pathway Name SMPDB ID
Smp00323 Quinidine Pathway SMP00323
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
Dosage forms
Form Route Strength
Solution Intramuscular
Tablet Oral
Tablet, extended release Oral
Prices
Unit description Cost Unit
Quinidine gluc 80 mg/ml vial 2.16 USD ml
Quinidine sulfate crystals 1.58 USD g
QuiNIDine Gluconate CR 324 mg Controlled Release Tabs 0.97 USD tab
Quinidine gluc er 324 mg tab 0.93 USD each
Quinidine Sulfate 300 mg 0.41 USD tablet
Quinidine sulfate 300 mg tablet 0.4 USD tablet
Quinidine Sulfate 200 mg 0.22 USD tablet
Quinidine sulfate 200 mg tablet 0.21 USD tablet
Patents Not Available
Properties
State solid
Melting point 174 oC
Experimental Properties
Property Value Source
water solubility 140 mg/L PhysProp
logP 2.6 PhysProp
logS -3.37 [ADME Research, USCD] PhysProp
Caco2 permeability -4.69 [ADME Research, USCD] BiGG
pKa 8.56 Various sources
Predicted Properties
Property Value Source
water solubility 3.34e-01 g/l ALOGPS
logP 2.82 ALOGPS
logP 2.51 ChemAxon Molconvert
logS -2.99 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 45.59 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 94.69 ChemAxon Molconvert
polarizability 35.82 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C06527 Link_out
PubChem Compound 441074 Link_out
PubChem Substance 46505356 Link_out
ChemSpider 389880 Link_out
ChEBI 28593 Link_out
ChEMBL 28593 Link_out
Therapeutic Targets Database DAP000515 Link_out
PharmGKB PA451209 Link_out
Drug Product Database 497525 Link_out
RxList http://www.rxlist.com/cgi/generic/quinidine.htm Link_out
Drugs.com http://www.drugs.com/cdi/quinidine-gluconate-controlled-release-tablets.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Quinidine Link_out
ATC Codes
  • C01BA01
AHFS Codes
  • 24:04.04.04
PDB Entries Not Available
FDA label show (614.9 KB)
MSDS show (73 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Preferably take on an ampty stomach.
Targets

1. Sodium channel protein type 5 subunit alpha

Pharmacological action: yes
Actions: inhibitor

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 responsible for the initial upstroke of the action potential in the electrocardiogram

Organism class: human
UniProt ID: Q14524 Link_out
Gene: SCN5A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. Grant AO: Electrophysiological basis and genetics of Brugada syndrome. J Cardiovasc Electrophysiol. 2005 Sep;16 Suppl 1:S3-7. Pubmed
  4. Napolitano C, Priori SG: Brugada syndrome. Orphanet J Rare Dis. 2006 Sep 14;1:35. Pubmed
  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
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  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. Pubmed
  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

2. Potassium channel subfamily K member 1

Pharmacological action: unknown
Actions: inhibitor

Weakly inward rectifying potassium channel

Organism class: human
UniProt ID: O00180 Link_out
Gene: KCNK1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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

3. Potassium channel subfamily K member 6

Pharmacological action: unknown
Actions: inhibitor

Exhibits outward rectification in a physiological K(+) gradient and mild inward rectification in symmetrical K(+) conditions

Organism class: human
UniProt ID: Q9Y257 Link_out
Gene: KCNK6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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. Epub 2008 Jun 8. Pubmed

4. Potassium voltage-gated channel subfamily H member 2

Pharmacological action: unknown
Actions: inhibitor

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 delayed rectifying potassium current in heart (IKr). Isoform 3 has no channel activity by itself, but modulates channel characteristics when associated with isoform 1

Organism class: human
UniProt ID: Q12809 Link_out
Gene: KCNH2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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
  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
  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. Epub 2008 Jun 8. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate, inhibitor, inducer

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 xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. 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. Epub 2009 Nov 24. Pubmed
  4. 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

2. Cytochrome P450 3A7

Actions: substrate

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 unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

3. Cytochrome P450 2D6

Actions: inhibitor

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 antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  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. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 1A2

Actions: inhibitor

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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 2E1

Actions: substrate

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 or carcinogenic forms

UniProt ID: P05181 Link_out
Gene: CYP2E1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 1A1

Actions: inhibitor

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 unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P04798 Link_out
Gene: CYP1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed

7. Cytochrome P450 2B6

Actions: inhibitor

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 unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20813 Link_out
Gene: CYP2B6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed

8. Cytochrome P450 2C8

Actions: substrate

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 unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed

9. Cytochrome P450 2C9

Actions: substrate, inhibitor

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 unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed
Transporters

1. Solute carrier family 22 member 2

Actions: inhibitor

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-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity

UniProt ID: O15244 Link_out
Gene: SLC22A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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

2. Solute carrier family 22 member 1

Actions: substrate, inhibitor

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, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin- dependent kinase II and LCK tyrosine kinase

UniProt ID: O15245 Link_out
Gene: SLC22A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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

3. Organic cation/carnitine transporter 2

Actions: inhibitor

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 cations such as tetraethylammonium (TEA) without the involvement of sodium. Also Relative uptake activity ratio of carnitine to TEA is 11.3

UniProt ID: O76082 Link_out
Gene: SLC22A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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

4. Bile salt export pump

Actions: inhibitor

Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes

UniProt ID: O95342 Link_out
Gene: ABCB11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites. Pharm Res. 2003 Apr;20(4):537-44. Pubmed

5. Multidrug resistance protein 1

Actions: substrate, inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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. Epub 2009 Jul 21. Pubmed
  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. Epub 2009 Jun 18. Pubmed
  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. Epub 2009 Mar 25. Pubmed
  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
  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
  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
  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
  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
  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

6. Solute carrier organic anion transporter family member 1A2

Actions: inhibitor

Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity)

UniProt ID: P46721 Link_out
Gene: SLCO1A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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

7. Solute carrier family 22 member 8

Actions: inhibitor

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, fexofenadine. Transports benzylpenicillin (PCG), estrone- 3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA)

UniProt ID: Q8TCC7 Link_out
Gene: SLC22A8 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

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

8. Canalicular multispecific organic anion transporter 1

Actions: inhibitor

Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter

UniProt ID: Q92887 Link_out
Gene: ABCC2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

9. Organic cation/carnitine transporter 1

Actions: inhibitor

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 the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 1.78. A key substrate of this transporter seems to be ergothioneine (ET)

UniProt ID: Q9H015 Link_out
Gene: SLC22A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

10. Solute carrier organic anion transporter family member 1B1

Actions: inhibitor

Mediates the Na(+)-independent transport of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. May play an important role in the clearance of bile acids and organic anions from the liver

UniProt ID: Q9Y6L6 Link_out
Gene: SLCO1B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Carriers

1. Alpha-1-acid glycoprotein 1

Appears to function in modulating the activity of the immune system during the acute-phase reaction

UniProt ID: P02763 Link_out
Gene: ORM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
Comments
Drug created on June 13, 2005 07:24 / Updated on August 12, 2011 09:01

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.