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Identification
Name Ouabain
Accession Number DB01092 (APRD00135)
Type small molecule
Groups approved
Description

A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like digitalis. It is commonly used in cell biological studies as an inhibitor of the NA-K(+)-exchanging ATPase. [PubChem]

Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
G-Strophanthin
Ouabagenin L-Rhamnoside
Ouabain Octahydrate
Ouabain, Octahydrate
Ouabaine
Strophanthin G
Strophanthin-G
Salts Not Available
Brand names
Name Company
Acocantherin
Astrobain
G-Strophicor
Gratibain
Gratus Strophanthin
Kombetin
Purostrophan
Rectobaina
Solufantina
Strodival
Strophalen
Strophoperm
Strophosan
Uabaina
Uabanin
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Brand mixtures Not Available
Categories
  • Enzyme Inhibitors
  • Cardiotonic Agents
CAS number 630-60-4
Weight Average: 584.6525
Monoisotopic: 584.283276872
Chemical Formula C29H44O12
InChI Key InChIKey=LPMXVESGRSUGHW-HBYQJFLCSA-N
InChI
InChI=1S/C29H44O12/c1-13-22(34)23(35)24(36)25(40-13)41-15-8-19(32)28(12-30)21-17(3-5-27(28,37)9-15)29(38)6-4-16(14-7-20(33)39-11-14)26(29,2)10-18(21)31/h7,13,15-19,21-25,30-32,34-38H,3-6,8-12H2,1-2H3/t13-,15-,16+,17+,18+,19+,21+,22-,23+,24+,25-,26+,27-,28+,29-/m0/s1
Plain Text
IUPAC Name
4-[(1S,2R,3R,5S,7S,10R,11S,14R,15R,17R)-3,7,11,17-tetrahydroxy-2-(hydroxymethyl)-15-methyl-5-{[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy}tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadecan-14-yl]-2,5-dihydrofuran-2-one
SMILES
[H][C@@]12CC[C@]3(O)C[C@H](C[C@@H](O)[C@]3(CO)[C@@]1([H])[C@H](O)C[C@]1(C)[C@H](CC[C@]21O)C1=CC(=O)OC1)O[C@@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@H]1O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Steroids and Steroid Derivatives
Substructures
  • Steroids and Steroid Derivatives
  • Carboxylic Acids and Derivatives
  • Glycerol and Derivatives
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Pyrans
  • Acetates
  • Acetals and Derivatives
  • Sterols
  • Lactones
  • Carbohydrates
  • Ethers
  • Bicyclohexanes
  • Alcohols and Polyols
  • Heterocyclic compounds
Pharmacology
Indication For the treatment of atrial fibrillation and flutter and heart failure
Pharmacodynamics Ouabain, a cardiac glycoside similar to digitoxin, is used to treat congestive heart failure and supraventricular arrhythmias due to reentry mechanisms, and to control ventricular rate in the treatment of chronic atrial fibrillation.
Mechanism of action Ouabain inhibits the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium and calcium concentrations. Increased intracellular concentrations of calcium may promote activation of contractile proteins (e.g., actin, myosin). Ouabain also acts on the electrical activity of the heart, increasing the slope of phase 4 depolarization, shortening the action potential duration, and decreasing the maximal diastolic potential.
Absorption Not Available
Volume of distribution Not Available
Protein binding 60%
Metabolism Not Available
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms Not Available
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 200 °C PhysProp
water solubility 1.03E+004 mg/L Not Available
logP -2.00 SANGSTER (1994)
Predicted Properties
Property Value Source
water solubility 4.61e+00 g/l ALOGPS
logP -1 ALOGPS
logP -2.8 ChemAxon
logS -2.1 ALOGPS
pKa (strongest acidic) 7.18 ChemAxon
pKa (strongest basic) -2.9 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 11 ChemAxon
hydrogen donor count 8 ChemAxon
polar surface area 206.6 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 140.83 ChemAxon
polarizability 59.93 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Gao J, Wymore RS, Wang Y, Gaudette GR, Krukenkamp IB, Cohen IS, Mathias RT: Isoform-specific stimulation of cardiac Na/K pumps by nanomolar concentrations of glycosides. J Gen Physiol. 2002 Apr;119(4):297-312. Pubmed
  2. Saunders R, Scheiner-Bobis G: Ouabain stimulates endothelin release and expression in human endothelial cells without inhibiting the sodium pump. Eur J Biochem. 2004 Mar;271(5):1054-62. Pubmed
  3. Hamlyn JM, Blaustein MP, Bova S, DuCharme DW, Harris DW, Mandel F, Mathews WR, Ludens JH: Identification and characterization of a ouabain-like compound from human plasma. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6259-63. Pubmed
  4. Hamlyn JM, Laredo J, Shah JR, Lu ZR, Hamilton BP: 11-hydroxylation in the biosynthesis of endogenous ouabain: multiple implications. Ann N Y Acad Sci. 2003 Apr;986:685-93. Pubmed
  5. Laredo J, Hamilton BP, Hamlyn JM: Ouabain is secreted by bovine adrenocortical cells. Endocrinology. 1994 Aug;135(2):794-7. Pubmed
External Links
Resource Link
KEGG Drug D00112 Link_out
KEGG Compound C01443 Link_out
PubChem Compound 439501 Link_out
PubChem Substance 46505479 Link_out
ChemSpider 388599 Link_out
ChEBI 472805 Link_out
ChEMBL 472805 Link_out
Therapeutic Targets Database DAP000465 Link_out
PharmGKB PA163522138 Link_out
Wikipedia http://en.wikipedia.org/wiki/Ouabain Link_out
ATC Codes
  • C01AC01
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Sodium/potassium-transporting ATPase alpha-1 chain

Pharmacological action: yes
Actions: inhibitor

This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients

Organism class: human
UniProt ID: P05023 Link_out
Gene: ATP1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mentre P, Debey P: An unexpected effect of an ouabain-sensitive ATPase activity on the amount of antigen-antibody complexes formed in situ. Cell Mol Biol (Noisy-le-grand). 1999 Sep;45(6):781-91. Pubmed
  2. Qazzaz HM, El-Masri MA, Stolowich NJ, Valdes R Jr: Two biologically active isomers of dihydroouabain isolated from a commercial preparation. Biochim Biophys Acta. 1999 Nov 16;1472(3):486-97. Pubmed
  3. Tao QF, Hollenberg NK, Graves SW: Sodium pump inhibition and regional expression of sodium pump alpha-isoforms in lens. Hypertension. 1999 Nov;34(5):1168-74. Pubmed
  4. Hawke TJ, Willmets RG, Lindinger MI: K+ transport in resting rat hind-limb skeletal muscle in response to paraxanthine, a caffeine metabolite. Can J Physiol Pharmacol. 1999 Nov;77(11):835-43. Pubmed
  5. Almotrefi AA, Basco C, Moorji A, Dzimiri N: Class I antiarrhythmic drug effects on ouabain binding to guinea pig cardiac Na+ -K+ ATPase. Can J Physiol Pharmacol. 1999 Nov;77(11):866-70. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Enzymes

1. 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

Transporters

1. Solute carrier organic anion transporter family member 1A2

Actions: substrate, 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. Li L, Lee TK, Meier PJ, Ballatori N: Identification of glutathione as a driving force and leukotriene C4 as a substrate for oatp1, the hepatic sinusoidal organic solute transporter. J Biol Chem. 1998 Jun 26;273(26):16184-91. Pubmed
  2. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B: Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33. Pubmed
  3. Bossuyt X, Muller M, Meier PJ: Multispecific amphipathic substrate transport by an organic anion transporter of human liver. J Hepatol. 1996 Nov;25(5):733-8. Pubmed
  4. Hagenbuch B, Adler ID, Schmid TE: Molecular cloning and functional characterization of the mouse organic-anion-transporting polypeptide 1 (Oatp1) and mapping of the gene to chromosome X. Biochem J. 2000 Jan 1;345 Pt 1:115-20. Pubmed
  5. Bossuyt X, Muller M, Hagenbuch B, Meier PJ: Polyspecific drug and steroid clearance by an organic anion transporter of mammalian liver. J Pharmacol Exp Ther. 1996 Mar;276(3):891-6. Pubmed
  6. Eckhardt U, Schroeder A, Stieger B, Hochli M, Landmann L, Tynes R, Meier PJ, Hagenbuch B: Polyspecific substrate uptake by the hepatic organic anion transporter Oatp1 in stably transfected CHO cells. Am J Physiol. 1999 Apr;276(4 Pt 1):G1037-42. Pubmed

2. 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
  2. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. Pubmed

3. Solute carrier organic anion transporter family member 4C1

Actions: substrate

Organic anion transporter, capable of transporting pharmacological substances such as digoxin, ouabain, thyroxine, methotrexate and cAMP. May participate in the regulation of membrane transport of ouabain. Involved in the uptake of the dipeptidyl peptidase-4 inhibitor sitagliptin and hence may play a role in its transport into and out of renal proximal tubule cells. May be involved in the first step of the transport pathway of digoxin and various compounds into the urine in the kidney. May be involved in sperm maturation by enabling directed movement of organic anions and compounds within or between cells. This ion- transporting process is important to maintain the strict epididymal homeostasis necessary for sperm maturation. May have a role in secretory functions since seminal vesicle epithelial cells are assumed to secrete proteins involved in decapacitation by modifying surface proteins to facilitate the acquisition of the ability to fertilize the egg

UniProt ID: Q6ZQN7 Link_out
Gene: SLCO4C1 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mikkaichi T, Suzuki T, Onogawa T, Tanemoto M, Mizutamari H, Okada M, Chaki T, Masuda S, Tokui T, Eto N, Abe M, Satoh F, Unno M, Hishinuma T, Inui K, Ito S, Goto J, Abe T: Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3569-74. Epub 2004 Mar 1. Pubmed

4. Solute carrier organic anion transporter family member 1B3

Actions: substrate

Mediates the Na(+)-independent transport of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotrexate and sulfobromophthalein (BSP)

UniProt ID: Q9NPD5 Link_out
Gene: SLCO1B3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B: Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33. Pubmed

5. Solute carrier organic anion transporter family member 1C1

Actions: substrate

Mediates the Na(+)-independent high affinity transport of organic anions such as the thyroid hormones thyroxine (T4) and rT3. Other potential substrates, such as triiodothyronine (T3), 17-beta-glucuronosyl estradiol, estrone-3-sulfate and sulfobromophthalein (BSP) are transported with much lower efficiency

UniProt ID: Q9NYB5 Link_out
Gene: SLCO1C1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Pizzagalli F, Hagenbuch B, Stieger B, Klenk U, Folkers G, Meier PJ: Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter. Mol Endocrinol. 2002 Oct;16(10):2283-96. Pubmed

6. Solute carrier organic anion transporter family member 1B1

Actions: substrate

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. van Montfoort JE, Schmid TE, Adler ID, Meier PJ, Hagenbuch B: Functional characterization of the mouse organic-anion-transporting polypeptide 2. Biochim Biophys Acta. 2002 Aug 19;1564(1):183-8. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19