You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
Record Information
Version2.0
Creation Date2009-07-21 20:28:36 UTC
Update Date2014-12-24 20:25:55 UTC
Accession NumberT3D3015
Identification
Common NameOxymorphone
ClassSmall Molecule
DescriptionAn opioid analgesic with actions and uses similar to those of morphine, apart from an absence of cough suppressant activity. It is used in the treatment of moderate to severe pain, including pain in obstetrics. It may also be used as an adjunct to anesthesia. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1092)
Compound Type
  • Adjuvant
  • Adjuvant, Anesthesia
  • Amine
  • Analgesic
  • Analgesic, Opioid
  • Drug
  • Ether
  • Metabolite
  • Narcotic
  • Opiate Agonist
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
14-Hydroxydihydromorphinone
Dihydrohydroxymorphinone
Dihydroxymorphinone
EN3202
Numorphan
Opana
OPANA ER
Oximorphonum
Oxymorphine
Chemical FormulaC17H19NO4
Average Molecular Mass301.337 g/mol
Monoisotopic Mass301.131 g/mol
CAS Registry Number76-41-5
IUPAC Name(1S,5R,13R,17S)-10,17-dihydroxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0¹,¹³.0⁵,¹⁷.0⁷,¹⁸]octadeca-7(18),8,10-trien-14-one
Traditional Nameoxymorphone
SMILES[H][C@@]12OC3=C(O)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1(O)CCC2=O
InChI IdentifierInChI=1S/C17H19NO4/c1-18-7-6-16-13-9-2-3-10(19)14(13)22-15(16)11(20)4-5-17(16,21)12(18)8-9/h2-3,12,15,19,21H,4-8H2,1H3/t12-,15+,16+,17-/m1/s1
InChI KeyInChIKey=UQCNKQCJZOAFTQ-ISWURRPUSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as phenanthrenes and derivatives. These are polycyclic compounds containing a phenanthrene moiety, which is a tricyclic aromatic compound with three non-linearly fused benzene.
KingdomOrganic compounds
Super ClassBenzenoids
ClassPhenanthrenes and derivatives
Sub ClassNot Available
Direct ParentPhenanthrenes and derivatives
Alternative Parents
Substituents
  • Phenanthrene
  • Isoquinolone
  • Tetralin
  • Coumaran
  • 1-hydroxy-2-unsubstituted benzenoid
  • Alkyl aryl ether
  • Aralkylamine
  • Piperidine
  • Cyclic alcohol
  • Tertiary alcohol
  • 1,2-aminoalcohol
  • Ketone
  • Tertiary aliphatic amine
  • Tertiary amine
  • Ether
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organic nitrogen compound
  • Organopnictogen compound
  • Carbonyl group
  • Organooxygen compound
  • Alcohol
  • Organic oxygen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point248-249°C
Boiling PointNot Available
Solubility2.4E+004 mg/L
LogP0.83
Predicted Properties
PropertyValueSource
Water Solubility25.6 g/LALOGPS
logP1.26ALOGPS
logP0.78ChemAxon
logS-1.1ALOGPS
pKa (Strongest Acidic)7.34ChemAxon
pKa (Strongest Basic)10.93ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area70 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity79.56 m³·mol⁻¹ChemAxon
Polarizability30.77 ųChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4l-9050000000-d955cbd739d3bad18756JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-00c0-6907600000-2e98fd21eb80cd8204b3JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-0f89-0093000000-d20c48538ad6696fd83bJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0f89-0095000000-3fa32e9f5773ea0cc992JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-0091000000-4c5b42673e83312d1305JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-069u-3090000000-b1a88d98c02d968d1332JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0029000000-0f9dac6d2c5bb246b565JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0ue9-0097000000-2bab2cfd5aabe92e0abeJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-000x-2090000000-7d02b1358307dc0ce4d2JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0009000000-ab6f6c1d45a17ba966cdJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0ue9-0049000000-68376f76c73135dac7e3JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0uk9-0093000000-3e6504da4a5c1b25ff70JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0009000000-867b26b8e9b8bd5f9273JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udi-0009000000-867b26b8e9b8bd5f9273JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0udi-0097000000-9087b236d7dbdab76ba5JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-0udl-7932000000-89141254d526ca629dacJSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureEnteral(rectal).
Mechanism of ToxicityOxymorphone 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. Also, it has been shown that oxymorphone binds to and inhibits GABA inhibitory interneurons via mu-receptors. These interneurons normally inhibit the descending pain inhibition pathway. So, without the inhibitory signals, pain modulation can proceed downstream.
MetabolismOxymorphone undergoes extensive hepatic metabolism in humans. After a 10 mg oral dose, 49% was excreted over a five-day period in the urine. Of this, 82% was excreted in the first 24 hours after administration. The recovered drug-related products contained the oxymorphone (1.9%), the conjugate of oxymorphone (44.1%), the 6(beta)-carbinol produced by 6-keto reduction of oxymorphone (0.3%), and the conjugates of 6(beta)-carbinol (2.6%) and 6(alpha)-carbinol (0.1%). Route of Elimination: Oxymorphone is highly metabolized, principally in the liver, and undergoes reduction or conjugation with glucuronic acid to form both active and inactive products. Because oxymorphone is extensively metabolized, <1% of the administered dose is excreted unchanged in the urine. Half Life: 1.3 (+/-0.7) hours
Toxicity Values Intravenous mouse LD50 is 172 mg/kg.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of moderate-to-severe pain.
Minimum Risk LevelNot Available
Health EffectsMedical problems can include congested lungs, liver disease, tetanus, infection of the heart valves, skin abscesses, anemia and pneumonia. Death can occur from overdose.
SymptomsOxymorphone overdosage is characterized by respiratory depression, extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In a severe case of overdose, apnea, circulatory collapse, cardiac arrest, and death may occur.
TreatmentPrimary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and the institution of assisted or controlled ventilation. The opioid antagonist naloxone hydrochloride is a specific antidote against respiratory depression which may result from overdosage or unusual sensitivity to opioids including oxymorphone. Therefore, an appropriate dose of naloxone hydrochloride should be administered (usual initial adult dose 0.4 mg-2 mg) preferably by the intravenous route and simultaneously with efforts at respiratory resuscitation. Since the duration of action of oxymorphone may exceed that of the antagonist, the patient should be kept under continued surveillance and repeated doses of the antagonist should be administered as needed to maintain adequate respiration. Naloxone hydrochloride should not be administered in the absence of clinically significant respiratory or cardiovascular depression. In addition, it should be considered that the use of an opioid antagonist in patients physically dependent on opioids may precipitate an acute withdrawal syndrome that cannot be readily suppressed while the action of the antagonist persists. If respiratory depression is associated with muscular rigidity, administration of a neuromuscular blocking agent may be necessary to facilitate assisted or controlled ventilation. Muscular rigidity may also respond to opioid antagonist therapy. Oxygen, intravenous fluids, vasopressors and other supportive measures should be employed as indicated. (4)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01192
HMDB IDHMDB15323
PubChem Compound ID5284604
ChEMBL IDCHEMBL963
ChemSpider ID4447650
KEGG IDC08019
UniProt IDNot Available
OMIM ID
ChEBI ID194484
BioCyc IDNot Available
CTD IDNot Available
Stitch IDOxymorphone
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkOxymorphone
References
Synthesis Reference

Bao-Shan Huang, Yansong Lu, Ben-Yi Ji, Aris P Christodoulou, “Preparation of oxymorphone from morphine.” U.S. Patent US5922876, issued May, 1992.

MSDSLink
General References
  1. Martindale. The Extra Pharmacopoeia, 30th ed.
  2. Drugs.com [Link]
  3. Drugs.com [Link]
  4. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors. The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extend to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B. Also couples to adenylate cyclase stimulatory G alpha proteins. The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization. Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction. The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins. The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation. Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling. Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling. Endogenous ligands induce rapid desensitization, endocytosis and recycling whereas morphine induces only low desensitization and endocytosis. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 12 couples to GNAS and is proposed to be involved in excitatory effects. Isoform 16 and isoform 17 do not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity.
Gene Name:
OPRM1
Uniprot ID:
P35372
Molecular Weight:
44778.855 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.00078 uMNot AvailableBindingDB 50001707
IC500.0014 uMNot AvailableBindingDB 50001707
References
  1. Spetea M, Nevin ST, Hosztafi S, Ronai AZ, Toth G, Borsodi A: Affinity profiles of novel delta-receptor selective benzofuran derivatives of non-peptide opioids. Neurochem Res. 1998 Sep;23(9):1211-6. [9712193 ]
  2. Lemberg KK, Kontinen VK, Siiskonen AO, Viljakka KM, Yli-Kauhaluoma JT, Korpi ER, Kalso EA: Antinociception by spinal and systemic oxycodone: why does the route make a difference? In vitro and in vivo studies in rats. Anesthesiology. 2006 Oct;105(4):801-12. [17006080 ]
  3. Chamberlin KW, Cottle M, Neville R, Tan J: Oral oxymorphone for pain management. Ann Pharmacother. 2007 Jul;41(7):1144-52. Epub 2007 Jun 26. [17595308 ]
  4. Halimi G, Devaux C, Clot-Faybesse O, Sampol J, Legof L, Rochat H, Guieu R: Modulation of adenosine concentration by opioid receptor agonists in rat striatum. Eur J Pharmacol. 2000 Jun 16;398(2):217-24. [10854833 ]
  5. Gardell LR, King T, Ossipov MH, Rice KC, Lai J, Vanderah TW, Porreca F: Opioid receptor-mediated hyperalgesia and antinociceptive tolerance induced by sustained opiate delivery. Neurosci Lett. 2006 Mar 20;396(1):44-9. Epub 2005 Dec 15. [16343768 ]
  6. Klein P, Nelson WL: O3-(2-carbomethoxyallyl) ethers of opioid ligands derived from oxymorphone, naltrexone, etorphine, diprenorphine, norbinaltorphimine, and naltrindole. Unexpected O3-dealkylation in the opioid radioligand displacement assay. J Med Chem. 1992 Nov 27;35(24):4589-94. [1335078 ]
  7. Archer S, Seyed-Mozaffari A, Ward S, Kosterlitz HW, Paterson SJ, McKnight AT, Corbett AD: 10-Ketonaltrexone and 10-ketooxymorphone. J Med Chem. 1985 Jul;28(7):974-6. [2409281 ]
General Function:
Opioid receptor activity
Specific Function:
G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine.
Gene Name:
OPRD1
Uniprot ID:
P41143
Molecular Weight:
40368.235 Da
References
  1. Chamberlin KW, Cottle M, Neville R, Tan J: Oral oxymorphone for pain management. Ann Pharmacother. 2007 Jul;41(7):1144-52. Epub 2007 Jun 26. [17595308 ]
  2. Ananthan S, Khare NK, Saini SK, Seitz LE, Bartlett JL, Davis P, Dersch CM, Porreca F, Rothman RB, Bilsky EJ: Identification of opioid ligands possessing mixed micro agonist/delta antagonist activity among pyridomorphinans derived from naloxone, oxymorphone, and hydromorphone [correction of hydropmorphone]. J Med Chem. 2004 Mar 11;47(6):1400-12. [14998329 ]
General Function:
Opioid receptor activity
Specific Function:
G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions.
Gene Name:
OPRK1
Uniprot ID:
P41145
Molecular Weight:
42644.665 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.137 uMNot AvailableBindingDB 50001707
IC500.63 uMNot AvailableBindingDB 50001707
References
  1. Klein P, Nelson WL: O3-(2-carbomethoxyallyl) ethers of opioid ligands derived from oxymorphone, naltrexone, etorphine, diprenorphine, norbinaltorphimine, and naltrindole. Unexpected O3-dealkylation in the opioid radioligand displacement assay. J Med Chem. 1992 Nov 27;35(24):4589-94. [1335078 ]
  2. Archer S, Seyed-Mozaffari A, Ward S, Kosterlitz HW, Paterson SJ, McKnight AT, Corbett AD: 10-Ketonaltrexone and 10-ketooxymorphone. J Med Chem. 1985 Jul;28(7):974-6. [2409281 ]