Identification

Name
Ethylmorphine
Accession Number
DB01466
Type
Small Molecule
Groups
Approved, 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
  • Dionine
  • Ethyl morphine
  • Ethylmorphine
External IDs
IDS-NE-005(SECT.2) / R05DA01
Product Ingredients
IngredientUNIICASInChI Key
Ethylmorphine hydrochlorideMFM5450P3T125-30-4ZPPBASOODYCKDP-YZZSNFJZSA-N
International/Other Brands
Codethyline (Erfa) / Dionina (Merck) / Lepheton (Meda)
Categories
UNII
RWO67D87EU
CAS number
76-58-4
Weight
Average: 313.3908
Monoisotopic: 313.167793607
Chemical Formula
C19H23NO3
InChI Key
OGDVEMNWJVYAJL-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[9.6.1.0¹,¹³.0⁵,¹⁷.0⁷,¹⁸]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

Pharmacology

Indication

Ethylmorphine is an analgesic used for pain relief.

Pharmacodynamics

Ethylmorphine 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 action

Ethylmorphine 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.

TargetActionsOrganism
AMu-type opioid receptor
agonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

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

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Ethylmorphine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may increase the analgesic activities of Ethylmorphine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may increase the analgesic activities of Ethylmorphine.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may increase the analgesic activities of Ethylmorphine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may increase the analgesic activities of Ethylmorphine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Ethylmorphine is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when Ethylmorphine is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AbirateroneThe serum concentration of Ethylmorphine can be increased when it is combined with Abiraterone.
AcepromazineThe risk or severity of adverse effects can be increased when Ethylmorphine is combined with Acepromazine.
AceprometazineThe risk or severity of adverse effects can be increased when Ethylmorphine is combined with Aceprometazine.
AcetazolamideThe risk or severity of adverse effects can be increased when Ethylmorphine is combined with Acetazolamide.
Food Interactions
Not Available

References

General 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:7654478]
  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:9140136]
External Links
Human Metabolome Database
HMDB0015509
KEGG Drug
D07929
KEGG Compound
C07537
PubChem Compound
5359271
PubChem Substance
46505092
ChemSpider
4514250
ChEBI
4902
ChEMBL
CHEMBL1712170
Wikipedia
Ethylmorphine
ATC Codes
R05DA01 — EthylmorphineS01XA06 — Ethylmorphine

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)199-201 °CPhysProp
water solubility2610 mg/L (at 20 °C)SEIDELL,A (1941)
Predicted Properties
PropertyValueSource
Water Solubility0.835 mg/mLALOGPS
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 Area41.93 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity89.35 m3·mol-1ChemAxon
Polarizability34.17 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.995
Blood Brain Barrier+0.9981
Caco-2 permeable+0.7931
P-glycoprotein substrateSubstrate0.8987
P-glycoprotein inhibitor IInhibitor0.682
P-glycoprotein inhibitor IINon-inhibitor0.6396
Renal organic cation transporterInhibitor0.6561
CYP450 2C9 substrateNon-substrate0.8039
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateSubstrate0.7344
CYP450 1A2 substrateNon-inhibitor0.7851
CYP450 2C9 inhibitorNon-inhibitor0.8693
CYP450 2D6 inhibitorInhibitor0.6878
CYP450 2C19 inhibitorNon-inhibitor0.8318
CYP450 3A4 inhibitorNon-inhibitor0.8273
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5795
Ames testNon AMES toxic0.8526
CarcinogenicityNon-carcinogens0.9453
BiodegradationNot ready biodegradable0.9962
Rat acute toxicity2.6192 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7839
hERG inhibition (predictor II)Non-inhibitor0.6518
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 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

Taxonomy

Description
This compound belongs to the class of organic compounds known as 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.
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Morphinans
Sub Class
Not Available
Direct Parent
Morphinans
Alternative Parents
Phenanthrenes and derivatives / Tetralins / Coumarans / Aralkylamines / Alkyl aryl ethers / Piperidines / Trialkylamines / Secondary alcohols / Oxacyclic compounds / Azacyclic compounds
show 2 more
Substituents
Morphinan / Phenanthrene / Tetralin / Coumaran / Alkyl aryl ether / Aralkylamine / Piperidine / Benzenoid / Secondary alcohol / Tertiary amine
show 14 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
morphinane alkaloid (CHEBI:4902)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Voltage-gated calcium channel activity
Specific Function
Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone...
Gene Name
OPRM1
Uniprot ID
P35372
Uniprot Name
Mu-type opioid receptor
Molecular Weight
44778.855 Da
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:16530171]
  2. 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:16580639]
  3. 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:16580848]
  4. 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:16682505]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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. 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:7654478]
  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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, nad(p)h as one donor, and incorporation of one atom of oxygen
Specific Function
This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5.
Gene Name
POR
Uniprot ID
P16435
Uniprot Name
NADPH--cytochrome P450 reductase
Molecular Weight
76689.12 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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. 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 July 31, 2007 07:09 / Updated on September 21, 2018 00:12