Showing toxin card for Oxymorphone (T3D3015)

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Version	1.0
Creation Date	2009-07-21 20:28:36
Update Date	2010-05-18 21:01:38
Accession Number	T3D3015
Name	Oxymorphone
Compound Type	Adjuvant Adjuvant, Anesthesia Analgesic Analgesic, Opioid Drug Narcotic Opiate Agonist
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. (W533)
Synonyms	14-Hydroxydihydromorphinone Dihydrohydroxymorphinone Dihydroxymorphinone Oximorphonum Oxymorphine oxymorphone
Chemical IUPAC Name	10,17-dihydroxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7,9,11(18)-trien-14-one
Chemical Formula	C₁₇H₁₉NO₄
Chemical Structure
CAS Registry Number	76-41-5
InChI Identifier	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
InChI Key	InChIKey=UQCNKQCJZOAFTQ-UHFFFAOYSA-N
PubChem Compound ID	5284604
KEGG ID	C08019
UniProt ID	Not Available
OMIM ID	Not Available
ChEBI ID	Not Available
BioCyc ID	Not Available
SuperToxic ID	Not Available
CTD ID	Not Available
Stitch ID	Oxymorphone
DrugBank ID	DB01192
PDB ID	Not Available
ACToR ID	Not Available
Wikipedia Link	http://en.wikipedia.org/wiki/Oxymorphone
Monoisotopic Mass	301.131408
MOL File	Show
PDB File	Show
SDF File	Show
SMILES	CN1CCC23C4OC5=C2C(CC1C3(O)CCC4=O)=CC=C5O
Appearance	Not Available
Melting Point	248-249 oC
Solubility	2.4E+004 mg/L
Predicted LogP	0.7845
Route of Exposure	Enteral(rectal).
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.
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%).
Toxicity Values	LD50: 172 mg/kg (intravenous, mouse).
Lethal Dose	Not Available
Carcinogenicity (IARC Classification)	Not Available
Uses/Sources	Not Available
Minimum Risk Level	Not Available
Health Effects	Medical problems can include congested lungs, liver disease, tetanus, infection of the heart valves, skin abscesses, anemia and pneumonia. Death can occur from overdose.
Symptoms	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.
Treatment	Primary 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. (V650)
General References	W533 - Martindale. The Extra Pharmacopoeia, 30th ed. V111 - Drugs.com
Targets	Mu-type opioid receptor

Target 1 [top]

Target 1 ID

1155

Target 1 Name

Mu-type opioid receptor

Target 1 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.

Target 1 Description

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

Target 1 Synonyms

MOR-1

Target 1 Gene Name

OPRM1

Target 1 Protein Sequence

>Mu-type opioid receptor

MDSSAAPTNASNCTDALAYSSCSPAPSPGSWVNLSHLDGNLSDPCGPNRTDLGGRDSLCP
PTGSPSMITAITIMALYSIVCVVGLFGNFLVMYVIVRYTKMKTATNIYIFNLALADALAT
STLPFQSVNYLMGTWPFGTILCKIVISIDYYNMFTSIFTLCTMSVDRYIAVCHPVKALDF
RTPRNAKIINVCNWILSSAIGLPVMFMATTKYRQGSIDCTLTFSHPTWYWENLLKICVFI
FAFIMPVLIITVCYGLMILRLKSVRMLSGSKEKDRNLRRITRMVLVVVAVFIVCWTPIHI
YVIIKALVTIPETTFQTVSWHFCIALGYTNSCLNPVLYAFLDENFKRCFREFCIPTSSNI
EQQNSTRIRQNTRDHPSTANTVDRTNHQLENLEAETAPLP

Target 1 Number of Residues

400

Target 1 Molecular Weight

44778.9

Target 1 Theoretical pI

8.29

Target 1 GO Classification

Function
peptide receptor activity, G-protein coupled opioid receptor activity mu-opioid receptor activity signal transducer activity receptor activity transmembrane receptor activity G-protein coupled receptor activity rhodopsin-like receptor activity
Process
cellular process cell communication signal transduction cell surface receptor linked signal transduction G-protein coupled receptor protein signaling pathway
Component
cell membrane intrinsic to membrane integral to membrane

Target 1 General Function

Involved in mu-opioid receptor activity

Target 1 Pathways

Not Available

Target 1 Reactions

Not Available

Target 1 Signals

None

Target 1 Transmembrane Regions

67-96
106-123
146-165
196-211
237-259
283-305
314-330

Target 1 Essentiality

Non Essential

Target 1 Domain Function

PF00001:7tm_1

Target 1 GenBank ID Protein

Not Available

Target 1 UniProtKB ID

P35372

Target 1 Cellular Location

Cell membrane

Target 1 Gene Sequence

>1203 bp

ATGGACAGCAGCGCTGCCCCCACGAACGCCAGCAATTGCACTGATGCCTTGGCGTACTCA
AGTTGCTCCCCAGCACCCAGCCCCGGTTCCTGGGTCAACTTGTCCCACTTAGATGGCAAC
CTGTCCGACCCATGCGGTCCGAACCGCACCAACCTGGGCGGGAGAGACAGCCTGTGCCCT
CCGACCGGCAGTCCCTCCATGATCACGGCCATCACGATCATGGCCCTCTACTCCATCGTG
TGCGTGGTGGGGCTCTTCGGAAACTTCCTGGTCATGTATGTGATTGTCAGATACACCAAG
ATGAAGACTGCCACCAACATCTACATTTTCAACCTTGCTCTGGCAGATGCCTTAGCCACC
AGTACCCTGCCCTTCCAGAGTGTGAATTACCTAATGGGAACATGGCCATTTGGAACCATC
CTTTGCAAGATAGTGATCTCCATAGATTACTATAACATGTTCACCAGCATATTCACCCTC
TGCACCATGAGTGTTGATCGATACATTGCAGTCTGCCACCCTGTCAAGGCCTTAGATTTC
CGTACTCCCCGAAATGCCAAAATTATCAATGTCTGCAACTGGATCCTCTCTTCAGCCATT
GGTCTTCCTGTAATGTTCATGGCTACAACAAAATACAGGCAAGGTTCCATAGATTGTACA
CTAACATTCTCTCATCCAACCTGGTACTGGGAAAACCTCGTGAAGATCTGTGTTTTCATC
TTCGCCTTCATTATGCCAGTGCTCATCATTACCGTGTGCTATGGACTGATGATCTTGCGC
CTCAAGAGTGTCCGCATGCTCTCTGGCTCCAAAGAAAAGGACAGGAATCTTCGAAGGATC
ACCAGGATGGTGCTGGTGGTGGTGGCTGTGTTCATCGTCTGCTGGACTCCCATTCACATT
TACGTCATCATTAAAGCCTTGGTTACAATCCCAGAAACTACGTTCCAGACTGTTTCTTGG
CACTTCTGCATTGCTCTAGGTTACACAAACAGCTGCCTCAACCCAGTCCTTTATGCATTT
CTGGATGAAAACTTCAAACGATGCTTCAGAGAGTTCTGTATCCCAACCTCTTCCAACATT
GAGCAACAAAACTCCACTCGAATTCGTCAGAACACTAGAGACCACCCCTCCACGGCCAAT
ACAGTGGATAGAACTAATCATCAGCTAGAAAATCTGGAAGCAGAAACTGCTCCGTTGCCC
TAA

Target 1 GenBank Gene ID

Not Available

Target 1 GeneCard ID

OPRM1

Target 1 GenAtlas ID

OPRM1

Target 1 HGNC ID

HGNC:8156

Target 1 Chromosome Location

Not Available

Target 1 Locus

6q24-q25

Target 1 SNPs

SNPJam Report Link Image

Target 1 Toxin References

V113 - 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 ]
V116 - 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 ]
V114 - 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 ]
V112 - 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 ]
V115 - 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 ]

Target 1 General References

7905839; 7957926; 7891175; 12589820; 15893644; 19077058; 14702039

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