Identification

Name
Ethanolamine Oleate
Accession Number
DB06689
Type
Small Molecule
Groups
Approved
Description

Ethanolamine Oleate is a mild sclerosing agent. It is composed of ethanolamine, a basic substance, which when combined with oleic acid forms a clear, straw to pale yellow colored, deliquescent oleate.

Structure
Thumb
Synonyms
  • beta-Hydroxyethylammonium oleate
  • Ethanolamine oleate
  • Monoethanolamine oleate
  • Oldamin
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EthamolinInjection, solution50 mg/mLIntravenousQOL Medical, LLC.1998-12-22Not applicableUs
Ethanolamine Oleate Inj 50mg/mlLiquid50 mgIntravenousBlock Drug Company (Canada) Ltd.1992-12-312001-04-17Canada
International/Other Brands
Ethamolin / Monolate / Moramin / Neosclerol / Oldamin / Varicetin
Categories
UNII
U4RY8MRX7C
CAS number
2272-11-9
Weight
Average: 343.5444
Monoisotopic: 343.308644183
Chemical Formula
C20H41NO3
InChI Key
KGWDUNBJIMUFAP-KVVVOXFISA-N
InChI
InChI=1S/C18H34O2.C2H7NO/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18(19)20;3-1-2-4/h9-10H,2-8,11-17H2,1H3,(H,19,20);4H,1-3H2/b10-9-;
IUPAC Name
(9Z)-octadec-9-enoic acid; 2-aminoethan-1-ol
SMILES
NCCO.CCCCCCCC\C=C/CCCCCCCC(O)=O

Pharmacology

Indication

For the treatment of patients with esophageal varices that have recently bled, to prevent rebleeding.

Structured Indications
Pharmacodynamics

When injected intravenously, ethanolamine oleate acts primarily by irritation of the intimal endothelium of the vein and produces a sterile dose-related inflammatory response. This results in fibrosis and possible occlusion of the vein. Ethanolamine oleate also rapidly diffuses through the venous wall and produces a dose-related extravascular inflammatory reaction.

Mechanism of action

The oleic acid component of ethanolamine oleate is responsible for the inflammatory response, and may also activate coagulation in vivo by release of tissue factor and activation of Hageman factor. The ethanolamine component, however, may inhibit fibrin clot formation by chelating calcium, so that a procoagulant action of ethanolamine oleate has not been demonstrated.

TargetActionsOrganism
UCalcium ions
chelator
Human
UCoagulation factor XII
activator
Human
Absorption

After injection into an esophageal varix, ethanolamine oleate is cleared from the injection site within five minutes via the portal vein. Some of the medication also flows into the azygos vein through the periesophageal vein if more than 20 mL is injected.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

The minimum lethal dose administered intravenously to rabbits is 130 mg/kg. Overdosage can result in severe intramural necrosis of the esophagus. Complications resulting from such overdosage have resulted in death. LD50 (intravenous) in rats is 156 mg/kg. LD50 (intravenous) in dogs is 175 mg/kg.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
ClotrimazoleThe metabolism of Ethanolamine Oleate can be decreased when combined with Clotrimazole.Approved, Vet Approved
Cyproterone acetateThe serum concentration of Ethanolamine Oleate can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
IsoniazidThe metabolism of Ethanolamine Oleate can be decreased when combined with Isoniazid.Approved
NicotineThe metabolism of Ethanolamine Oleate can be decreased when combined with Nicotine.Approved
TiclopidineThe metabolism of Ethanolamine Oleate can be decreased when combined with Ticlopidine.Approved
Food Interactions
Not Available

References

General References
  1. NOORDIJK JA: [Monoethanolamine oleate]. Ned Tijdschr Geneeskd. 1950 Apr 22;94(16):1110-1. [PubMed:15416877]
  2. Howard ER, Stamatakis JD, Mowat AP: Management of esophageal varices in children by injection sclerotherapy. J Pediatr Surg. 1984 Feb;19(1):2-5. [PubMed:6607986]
  3. PACCA ML: [Antihyaluronidase activity of monoethanolamine oleate]. Boll Soc Ital Biol Sper. 1951 Mar-Apr;27(4):576-9. [PubMed:14869471]
  4. Zuberi BF, Baloch Q: Comparison of endoscopic variceal sclerotherapy alone and in combination with octreotide in controlling acute variceal hemorrhage and early rebleeding in patients with low-risk cirrhosis. Am J Gastroenterol. 2000 Mar;95(3):768-71. [PubMed:10710072]
  5. VOIGT J: [Allergy to varex (monoethanolamine oleate)]. Ugeskr Laeger. 1954 Mar 25;116(12):452-7. [PubMed:13169341]
  6. Meirelles-Santos JO, Carvalho AF Jr, Callejas-Neto F, Magna LA, Yamanaka A, Zeitune JM, Brandalise NA, Ferraz JG: Absolute ethanol and 5% ethanolamine oleate are comparable for sclerotherapy of esophageal varices. Gastrointest Endosc. 2000 May;51(5):573-6. [PubMed:10805844]
  7. Masaki M, Mitsuhashi H, Kondo Y, Suzuki S, Wada T: [Effects of embolizing agent (ethanolamine oleate; EO) on esophageal varices with special reference to endothelial injury]. Nihon Shokakibyo Gakkai Zasshi. 1984 Jun;81(6):1491. [PubMed:6471550]
  8. Seidman E, Weber AM, Morin CL, Ethier R, Lamarche JB, Guerguerian AJ, Geoffroy G, Roy CC: Spinal cord paralysis following sclerotherapy for esophageal varices. Hepatology. 1984 Sep-Oct;4(5):950-4. [PubMed:6332769]
  9. Takuma Y, Nouso K, Takayama H, Makino Y, Saito S, Tanaka S, Ogata M, Ohta T, Kubota J, Iwamuro M: Gastric ulcer after prophylactic balloon-occluded retrograde transvenous obliteration. J Gastroenterol. 2007 Mar;42(3):257-60. Epub 2007 Mar 30. [PubMed:17380286]
  10. VOIGT J: [Fatal allergic shock after injection of Varex (monoethanolamine-oleate). On the risks of injection treatment]. Ugeskr Laeger. 1963 Jun 21;125:896-8. [PubMed:13997698]
  11. Yamamoto K, Sakaguchi H, Anai H, Tanaka T, Morimoto K, Kichikawa K, Uchida H: Sclerotherapy for simple cysts with use of ethanolamine oleate: preliminary experience. Cardiovasc Intervent Radiol. 2005 Nov-Dec;28(6):751-5. [PubMed:16132390]
  12. Kang JH, Kambayashi J, Sakon M, Shiozaki H, Ogawa Y, Ohshiro T, Mori T: Mechanism of the haemostatic effect of ethanolamine oleate in the injection sclerotherapy for oesophageal varices. Br J Surg. 1987 Jan;74(1):50-3. [PubMed:3828735]
External Links
Human Metabolome Database
HMDB15638
KEGG Drug
D02276
PubChem Compound
5282489
PubChem Substance
99443246
ChemSpider
4445632
ChEMBL
CHEMBL1200394
PharmGKB
PA164746758
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Monoethanolamine_oleate
ATC Codes
C05BB01 — Monoethanolamine oleate

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2WithdrawnSupportive CareChronic Myeloproliferative Disorders / Infection NOS / Leukemias / Lymphoproliferative Disorders / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms / Unspecified Adult Solid Tumor, Protocol Specific1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
FormRouteStrength
Injection, solutionIntravenous50 mg/mL
LiquidIntravenous50 mg
Prices
Unit descriptionCostUnit
Ethamolin 5% ampul86.62USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
logP6.78ChemAxon
pKa (Strongest Acidic)4.99ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count16ChemAxon
Refractivity87.4 m3·mol-1ChemAxon
Polarizability37.09 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9805
Blood Brain Barrier-0.6473
Caco-2 permeable-0.5672
P-glycoprotein substrateSubstrate0.6703
P-glycoprotein inhibitor INon-inhibitor0.959
P-glycoprotein inhibitor IINon-inhibitor0.9592
Renal organic cation transporterNon-inhibitor0.8873
CYP450 2C9 substrateNon-substrate0.853
CYP450 2D6 substrateNon-substrate0.7411
CYP450 3A4 substrateNon-substrate0.7548
CYP450 1A2 substrateInhibitor0.6639
CYP450 2C9 inhibitorNon-inhibitor0.9248
CYP450 2D6 inhibitorNon-inhibitor0.8421
CYP450 2C19 inhibitorNon-inhibitor0.9104
CYP450 3A4 inhibitorNon-inhibitor0.8594
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9496
Ames testNon AMES toxic0.9378
CarcinogenicityNon-carcinogens0.8135
BiodegradationReady biodegradable0.7487
Rat acute toxicity1.5407 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9046
hERG inhibition (predictor II)Non-inhibitor0.8212
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted 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

Taxonomy

Description
This compound belongs to the class of organic compounds known as long-chain fatty acids. These are fatty acids with an aliphatic tail that contains between 13 and 21 carbon atoms.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Fatty Acyls
Sub Class
Fatty acids and conjugates
Direct Parent
Long-chain fatty acids
Alternative Parents
Unsaturated fatty acids / Straight chain fatty acids / Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Long-chain fatty acid / Unsaturated fatty acid / Straight chain fatty acid / Monocarboxylic acid or derivatives / Carboxylic acid / Carboxylic acid derivative / Organic oxygen compound / Organic oxide / Hydrocarbon derivative / Organooxygen compound
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Small molecule
Organism
Human
Pharmacological action
Unknown
Actions
Chelator
References
  1. Kang JH, Kambayashi J, Sakon M, Shiozaki H, Ogawa Y, Ohshiro T, Mori T: Mechanism of the haemostatic effect of ethanolamine oleate in the injection sclerotherapy for oesophageal varices. Br J Surg. 1987 Jan;74(1):50-3. [PubMed:3828735]
  2. Yoshida T, Hayashi N, Nishimura S, Itoh T, Kawahara K, Okita K, Okazaki Y, Takemoto T: Mechanism of action of ethanolamine oleate used in injection sclerotherapy with special emphasis on the bronze varices. J Gastroenterol Hepatol. 1989;4 Suppl 1:173-5. [PubMed:2519043]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Activator
General Function
Serine-type endopeptidase activity
Specific Function
Factor XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. Prekallikrein is cleaved by factor XII t...
Gene Name
F12
Uniprot ID
P00748
Uniprot Name
Coagulation factor XII
Molecular Weight
67791.53 Da
References
  1. Takada K, Matsumoto A, Miyoshi H, Oshiba S: Changes in thrombin-antithrombin III complex after endoscopic injection sclerotherapy. Am J Gastroenterol. 1991 Jan;86(1):123-4. [PubMed:1986546]
  2. Kang JH, Kambayashi J, Sakon M, Shiozaki H, Ogawa Y, Ohshiro T, Mori T: Mechanism of the haemostatic effect of ethanolamine oleate in the injection sclerotherapy for oesophageal varices. Br J Surg. 1987 Jan;74(1):50-3. [PubMed:3828735]

Enzymes

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]

Drug created on August 24, 2008 14:08 / Updated on November 09, 2017 03:54