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Identification
Name Oxymorphone
Accession Number DB01192 (APRD00158)
Type small molecule
Groups approved
Description

An 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)
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • 14-Hydroxydihydromorphinone
  • Dihydrohydroxymorphinone
  • Dihydroxymorphinone
  • EN3202
  • Oximorphonum
  • Oxymorphine
  • oxymorphone
Brand names
  • Numorphan
  • Opana
  • OPANA ER
Brand name mixtures Not Available
Categories
  • Narcotics
  • Analgesics
  • Adjuvants, Anesthesia
  • Opiate Agonists
  • Analgesics, Opioid
  • Adjuvants
CAS number 76-41-5
Weight Average: 301.3371
Monoisotopic: 301.131408101
Chemical Formula C17H19NO4
InChI Key InChIKey=UQCNKQCJZOAFTQ-ISWURRPUSA-N
InChI
InChI=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
Plain Text
IUPAC Name
(1S,5R,13R,17S)-10,17-dihydroxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7(18),8,10-trien-14-one
SMILES
[H][C@@]12OC3=C(O)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1(O)CCC2=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Morphinans
  • Benzylisoquinolines
Substructures
  • Morphinans
  • Benzofurans
  • Hydroxy Compounds
  • Naphthalenes
  • Phenols and Derivatives
  • Benzylisoquinolines
  • Ethers
  • Benzene and Derivatives
  • Phenylpiperidines
  • Methoxyphenols
  • Aliphatic and Aryl Amines
  • Alcohols and Polyols
  • Phenanthrenes
  • Catechols
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Phenylpropylamines
  • (Iso)quinolines and Derivatives
  • Cyclohexenes and Derivatives
  • Phenyl Esters
  • Amphetamines
  • Catecholamines and Derivatives
  • Piperidines
  • Ketones
Pharmacology
Indication For the treatment of moderate-to-severe pain.
Pharmacodynamics Oxymorphone is a semi-synthetic opioid substitute for morphine. It is a potent analgesic. Opioid analgesics exert their principal pharmacologic effects on the CNS and the gastrointestinal tract. The principal actions of therapeutic value are analgesia and sedation. Opioids produce respiratory depression by direct action on brain stem respiratory centers. 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.
Mechanism of action Oxymorphone 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.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism

Oxymorphone 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%).

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 2D6 oxymorphone O-demethylation
Cytochrome P450 2D6 beta-oxymorphol O-demethylation
Cytochrome P450 2D6 alpha-oxycodol 6-ketoreduction
Cytochrome P450 2D6 beta-oxycodol 6-ketoreduction
Cytochrome P450 3A4 noroxycodone N-demethylation
Cytochrome P450 3A4 noroxymorphone N-demethylation
Cytochrome P450 3A4 alpha-noroxycodol N-demethylation
Cytochrome P450 3A4 beta-noroxycodol N-demethylation
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
Clearance Not Available
Toxicity Oxymorphone 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. Intravenous mouse LD50 is 172 mg/kg.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00412 Oxymorphone Pathway SMP00412
Pharmacoeconomics
Manufacturers
  • Endo pharmaceuticals inc
  • Impax laboratories inc
Packagers
Dosage forms
Form Route Strength
Suppository Rectal
Prices
Unit description Cost Unit
Opana er 40 mg tablet 21.82 USD tablet
Opana er 30 mg tablet 17.39 USD tablet
Opana ER 40 mg 12 Hour tablet 12.42 USD tablet
Opana er 20 mg tablet 12.12 USD tablet
Opana ER 30 mg 12 Hour tablet 9.76 USD tablet
Opana er 15 mg tablet 9.26 USD tablet
Opana ER 20 mg 12 Hour tablet 7.17 USD tablet
Opana ER 15 mg 12 Hour tablet 5.82 USD tablet
Opana er 5 mg tablet 5.53 USD tablet
Opana ER 10 mg 12 Hour tablet 4.4 USD tablet
Opana er 10 mg tablet 3.95 USD tablet
Opana ER 7.5 mg 12 Hour tablet 3.3 USD tablet
Numorphan 1 mg/ml ampul 3.13 USD ml
Opana er 7.5 mg tablet 3.0 USD tablet
Opana ER 5 mg 12 Hour tablet 2.3 USD tablet
Patents
Country Patent Number Approved Expires
United States 7276250 2003-02-04 2023-02-04
United States 5662933 1993-09-09 2013-09-09
Properties
State solid
Melting point 248-249 oC
Experimental Properties
Property Value Source
water solubility 2.4E+004 mg/L PhysProp
logP 0 PhysProp
pKa 8.17 Various sources
Predicted Properties
Property Value Source
water solubility 2.56e+01 g/l ALOGPS
logP 1.26 ALOGPS
logP 0.78 ChemAxon Molconvert
logS -1.07 ALOGPS
pKa 13.58 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 70.00 ChemAxon Molconvert
rotatable bond count 0 ChemAxon Molconvert
refractivity 79.56 ChemAxon Molconvert
polarizability 30.77 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C08019 Link_out
PubChem Compound 5284604 Link_out
PubChem Substance 46505296 Link_out
ChemSpider 4447650 Link_out
BindingDB 50001707 Link_out
Therapeutic Targets Database DAP001138 Link_out
PharmGKB PA450748 Link_out
Drug Product Database 1916505 Link_out
RxList http://www.rxlist.com/cgi/generic2/oxymorphone.htm Link_out
Drugs.com http://www.drugs.com/cdi/oxymorphone.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Oxymorphone Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (10 MB)
MSDS show (133 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Mu-type opioid receptor

Pharmacological action: yes
Actions: agonist

Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for beta-endorphin

Organism class: human
UniProt ID: P35372 Link_out
Gene: OPRM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Delta-type opioid receptor

Pharmacological action: unknown
Actions: antagonist

Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Highly stereoselective. receptor for enkephalins

Organism class: human
UniProt ID: P41143 Link_out
Gene: OPRD1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Gronlund J, Saari TI, Hagelberg NM, Neuvonen PJ, Olkkola KT, Laine K: Exposure to oral oxycodone is increased by concomitant inhibition of CYP2D6 and 3A4 pathways, but not by inhibition of CYP2D6 alone. Br J Clin Pharmacol. 2010 Jul;70(1):78-87. Pubmed
  2. Samer CF, Daali Y, Wagner M, Hopfgartner G, Eap CB, Rebsamen MC, Rossier MF, Hochstrasser D, Dayer P, Desmeules JA: The effects of CYP2D6 and CYP3A activities on the pharmacokinetics of immediate release oxycodone. Br J Pharmacol. 2010 Jun;160(4):907-18. Pubmed
  3. Lalovic B, Kharasch E, Hoffer C, Risler L, Liu-Chen LY, Shen DD: Pharmacokinetics and pharmacodynamics of oral oxycodone in healthy human subjects: role of circulating active metabolites. Clin Pharmacol Ther. 2006 May;79(5):461-79. Pubmed
  4. Adams M, Pieniaszek HJ Jr, Gammaitoni AR, Ahdieh H: Oxymorphone extended release does not affect CYP2C9 or CYP3A4 metabolic pathways. J Clin Pharmacol. 2005 Mar;45(3):337-45. Pubmed

2. Cytochrome P450 2D6

Actions: substrate

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 antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Gronlund J, Saari TI, Hagelberg NM, Neuvonen PJ, Olkkola KT, Laine K: Exposure to oral oxycodone is increased by concomitant inhibition of CYP2D6 and 3A4 pathways, but not by inhibition of CYP2D6 alone. Br J Clin Pharmacol. 2010 Jul;70(1):78-87. Pubmed
  2. Samer CF, Daali Y, Wagner M, Hopfgartner G, Eap CB, Rebsamen MC, Rossier MF, Hochstrasser D, Dayer P, Desmeules JA: The effects of CYP2D6 and CYP3A activities on the pharmacokinetics of immediate release oxycodone. Br J Pharmacol. 2010 Jun;160(4):907-18. Pubmed
  3. Lalovic B, Kharasch E, Hoffer C, Risler L, Liu-Chen LY, Shen DD: Pharmacokinetics and pharmacodynamics of oral oxycodone in healthy human subjects: role of circulating active metabolites. Clin Pharmacol Ther. 2006 May;79(5):461-79. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:46

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.