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Identification
NameEthylmorphine
Accession NumberDB01466
Typesmall molecule
Groupsapproved, illicit
Description

A narcotic analgesic and antitussive. It is metabolized in the liver by ethylmorphine-N-demethylase and used as an indicator of liver function. It is not marketed in the US but is approved for use in various countries around the world. In the US it is a schedule II drug (single-entity) and schedule III drug (in combination products).

Structure
Thumb
Synonyms
SynonymLanguageCode
DionineNot AvailableNot Available
Ethyl morphineNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
CodethylineErfa
DioninaMerck
LephetonMeda
Brand mixturesNot Available
Categories
CAS number76-58-4
WeightAverage: 313.3908
Monoisotopic: 313.167793607
Chemical FormulaC19H23NO3
InChI KeyOGDVEMNWJVYAJL-LEPYJNQMSA-N
InChI
InChI=1S/C19H23NO3/c1-3-22-15-7-4-11-10-13-12-5-6-14(21)18-19(12,8-9-20(13)2)16(11)17(15)23-18/h4-7,12-14,18,21H,3,8-10H2,1-2H3/t12-,13+,14-,18-,19-/m0/s1
IUPAC Name
(1S,5R,13R,14S,17R)-10-ethoxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7(18),8,10,15-tetraen-14-ol
SMILES
[H][C@@]12OC3=C(OCC)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1([H])C=C[C@@H]2O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassAlkaloids and Derivatives
ClassMorphinans
SubclassNot Available
Direct parentMorphinans
Alternative parentsBenzylisoquinolines; Phenanthrenes and Derivatives; Tetralins; Benzofurans; Phenol Ethers; Alkyl Aryl Ethers; Piperidines; Secondary Alcohols; Tertiary Amines; Polyamines
Substituentsphenanthrene; tetralin; benzofuran; phenol ether; alkyl aryl ether; benzene; piperidine; secondary alcohol; tertiary amine; ether; polyamine; amine; alcohol; organonitrogen compound
Classification descriptionThis compound belongs to the morphinans. These are polycyclic compounds with a four-ring skeleton with three condensed six-member rings forming a partially hydrogenated phenanthrene moiety, one of which is aromatic while the two others are alicyclic.
Pharmacology
IndicationEthylmorphine is an analgesic used for pain relief.
PharmacodynamicsEthylmorphine is metabolized by the enzyme cytochrome P450 2D6 to morphine. Morphine is a narcotic pain management agent indicated for the relief of pain in patients who require opioid analgesics for more than a few days. Morphine interacts predominantly with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, with high densities in the posterior amygdala, hypothalamus, thalamus, nucleus caudatus, putamen, and certain cortical areas. They are also found on the terminal axons of primary afferents within laminae I and II (substantia gelatinosa) of the spinal cord and in the spinal nucleus of the trigeminal nerve. In clinical settings, morphine exerts its principal pharmacological effect on the central nervous system and gastrointestinal tract. Its primary actions of therapeutic value are analgesia and sedation. Morphine appears to increase the patient's tolerance for pain and to decrease discomfort, although the presence of the pain itself may still be recognized. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Opioids also produce respiratory depression by direct action on brain stem respiratory centers.
Mechanism of actionEthylmorphine is metabolized by the liver enzyme cytochrome P450 2D6 to morphine. The precise mechanism of the analgesic action of morphine is unknown. However, specific CNS opiate receptors have been identified and likely play a role in the expression of analgesic effects. Morphine first acts on the mu-opioid receptors. The mechanism of respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to increases in carbon dioxide tension and to electrical stimulation. It has been shown that morphine binds to and inhibits GABA inhibitory interneurons. These interneurons normally inhibit the descending pain inhibition pathway. So, without the inhibitory signals, pain modulation can proceed downstream.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

After ingestion, ethylmorphine is converted to morphine in the human liver by the CYP450-isozyme CYP2D6, similarly to codeine.

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Ethylmorphine Action PathwayDrug actionSMP00681
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.995
Blood Brain Barrier + 0.9981
Caco-2 permeable + 0.7931
P-glycoprotein substrate Substrate 0.8987
P-glycoprotein inhibitor I Inhibitor 0.682
P-glycoprotein inhibitor II Non-inhibitor 0.6396
Renal organic cation transporter Inhibitor 0.6561
CYP450 2C9 substrate Non-substrate 0.8039
CYP450 2D6 substrate Substrate 0.8919
CYP450 3A4 substrate Substrate 0.7344
CYP450 1A2 substrate Non-inhibitor 0.7851
CYP450 2C9 substrate Non-inhibitor 0.8693
CYP450 2D6 substrate Inhibitor 0.6878
CYP450 2C19 substrate Non-inhibitor 0.8318
CYP450 3A4 substrate Non-inhibitor 0.8273
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5795
Ames test Non AMES toxic 0.8526
Carcinogenicity Non-carcinogens 0.9453
Biodegradation Not ready biodegradable 0.9962
Rat acute toxicity 2.6192 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.7839
hERG inhibition (predictor II) Non-inhibitor 0.6518
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point199-201 °CPhysProp
water solubility2610 mg/L (at 20 °C)SEIDELL,A (1941)
Predicted Properties
PropertyValueSource
water solubility8.35e-01 g/lALOGPS
logP1.72ALOGPS
logP1.7ChemAxon
logS-2.6ALOGPS
pKa (strongest acidic)13.78ChemAxon
pKa (strongest basic)9.19ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count1ChemAxon
polar surface area41.93ChemAxon
rotatable bond count2ChemAxon
refractivity89.35ChemAxon
polarizability34.17ChemAxon
number of rings5ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Aasmundstad TA, Xu BQ, Johansson I, Ripel A, Bjorneboe A, Christophersen AS, Bodd E, Morland J: Biotransformation and pharmacokinetics of ethylmorphine after a single oral dose. Br J Clin Pharmacol. 1995 Jun;39(6):611-20. Pubmed
  2. Xu BQ, Aasmundstad TA, Lillekjendlie B, Bjorneboe A, Christophersen AS, Morland J: Effects of ethanol on ethylmorphine metabolism in isolated rat hepatocytes: characterization by means of a multicompartmental model. Pharmacol Toxicol. 1997 Apr;80(4):171-81. Pubmed
External Links
ResourceLink
KEGG DrugD07929
KEGG CompoundC07537
PubChem Compound5359271
PubChem Substance46505092
ChemSpider4514250
WikipediaEthylmorphine
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Mu-type opioid receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Mu-type opioid receptor P35372 Details

References:

  1. Yamada H, Shimoyama N, Sora I, Uhl GR, Fukuda Y, Moriya H, Shimoyama M: Morphine can produce analgesia via spinal kappa opioid receptors in the absence of mu opioid receptors. Brain Res. 2006 Apr 14;1083(1):61-9. Epub 2006 Mar 10. Pubmed
  2. Kasai S, Han W, Ide S, Hata H, Takamatsu Y, Yamamoto H, Uhl GR, Sora I, Ikeda K: Involvement of the 3’ non-coding region of the mu opioid receptor gene in morphine-induced analgesia. Psychiatry Clin Neurosci. 2006 Apr;60 Suppl 1:S11-7. doi:10.1111/j.1440-1819.2006.01523.x-i1
  3. Choi HS, Kim CS, Hwang CK, Song KY, Wang W, Qiu Y, Law PY, Wei LN, Loh HH: The opioid ligand binding of human mu-opioid receptor is modulated by novel splice variants of the receptor. Biochem Biophys Res Commun. 2006 May 19;343(4):1132-40. Epub 2006 Mar 23. Pubmed
  4. Castro RR, Cunha FQ, Silva FS Jr, Rocha FA: A quantitative approach to measure joint pain in experimental osteoarthritis—evidence of a role for nitric oxide. Osteoarthritis Cartilage. 2006 Aug;14(8):769-76. Epub 2006 Mar 31. Pubmed
  5. Johnson EA, Oldfield S, Braksator E, Gonzalez-Cuello A, Couch D, Hall KJ, Mundell SJ, Bailey CP, Kelly E, Henderson G: Agonist-selective mechanisms of mu-opioid receptor desensitization in human embryonic kidney 293 cells. Mol Pharmacol. 2006 Aug;70(2):676-85. Epub 2006 May 8. 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 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Aasmundstad TA, Xu BQ, Johansson I, Ripel A, Bjorneboe A, Christophersen AS, Bodd E, Morland J: Biotransformation and pharmacokinetics of ethylmorphine after a single oral dose. Br J Clin Pharmacol. 1995 Jun;39(6):611-20. Pubmed
  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

2. NADPH--cytochrome P450 reductase

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
NADPH--cytochrome P450 reductase P16435 Details

3. Cytochrome P450 2B6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2B6 P20813 Details

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

4. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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 3A7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

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

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Drug created on July 31, 2007 07:09 / Updated on September 16, 2013 17:14