Hydrocodone

Common Name

Hydrocodone Description

Hydrocodone is only found in individuals that have used or taken this drug. It is a narcotic analgesic related to codeine, but more potent and more addicting by weight. It is used also as cough suppressant. [PubChem]Hydrocodone acts as a weak agonist at OP1, OP2, and OP3 opiate receptors within the central nervous system (CNS). Hydrocodone primarily affects OP3 receptors, which are coupled with G-protein receptors and function as modliators, both positive and negative, of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimliates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellliar cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine, and noradrenaline is inhibited. Opioids such as hydrocodone also inhibit the release of vasopressin, somatostatin, insliin, and glucagon. Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This reslits in hyperpolarization and reduced neuronal excitability. Structure

Synonyms

Value Source (-)-DihydrocodeinoneChEBI 4,5-alpha-Epoxy-3-methoxy-17-methylmorphinan-6-oneChEBI DihydrocodeinoneChEBI HidrocodonaChEBI HydrocodonChEBI HydrocodonumChEBI HydroconeChEBI HydroconumChEBI IdrocodoneChEBI 4,5-a-Epoxy-3-methoxy-17-methylmorphinan-6-oneGenerator 4,5-α-epoxy-3-methoxy-17-methylmorphinan-6-oneGenerator HyconMeSH CodinovoMeSH HycodanMeSH Hydrocodone tartrate (1:1), hydrate (2:5)MeSH Knoll brand OF hydrocodone tartrateMeSH Nourypharma brand OF hydrocodone tartrateMeSH Robins brand OF hydrocodone tartrateMeSH Wyeth brand OF hydrocodone tartrateMeSH DicodidMeSH Du pont brand OF hydrocodone tartrateMeSH HydrocodeinonebitartrateMeSH Hydrocodone bitartrateMeSH HydroconMeSH RobidoneMeSH

Chemical Formlia

C18H21NO3 Average Molecliar Weight

299.3642 Monoisotopic Molecliar Weight

299.152143543 IUPAC Name

(1S,5R,13R,17R)-10-methoxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0¹,¹³.0⁵,¹⁷.0⁷,¹⁸]octadeca-7(18),8,10-trien-14-one Traditional Name

hydrocodone CAS Registry Number

125-29-1 SMILES

[H][C@@]12OC3=C(OC)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1([H])CCC2=O

InChI Identifier

InChI=1S/C18H21NO3/c1-19-8-7-18-11-4-5-13(20)17(18)22-16-14(21-2)6-3-10(15(16)18)9-12(11)19/h3,6,11-12,17H,4-5,7-9H2,1-2H3/t11-,12+,17-,18-/m0/s1

InChI Key

LLPOLZWFYMWNKH-CMKMFDCUSA-N Chemical 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
  • Isoquinolones and derivatives
  • Tetralins
  • Coumarans
  • Anisoles
  • Aralkylamines
  • Alkyl aryl ethers
  • Piperidines
  • Trialkylamines
  • Ketones
  • Oxacyclic compounds
  • Azacyclic compounds
  • Organopnictogen compounds
  • Organic oxides
  • Hydrocarbon derivatives
  • Substituents

  • Morphinan
  • Phenanthrene
  • Isoquinolone
  • Tetralin
  • Coumaran
  • Anisole
  • Alkyl aryl ether
  • Aralkylamine
  • Piperidine
  • Benzenoid
  • Ketone
  • Tertiary amine
  • Tertiary aliphatic amine
  • Oxacycle
  • Ether
  • Azacycle
  • Organoheterocyclic compound
  • Amine
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxide
  • Organic nitrogen compound
  • Organopnictogen compound
  • Carbonyl group
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound
  • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

  • organic heteropentacyclic compound (CHEBI:5779 )
  • Ontology Status

    Expected but not Quantified Origin

  • Drug
  • Biofunction

  • Analgesics
  • Analgesics, Opioid
  • Antitussive Agents
  • Antitussives
  • Narcotics
  • Application

  • Pharmaceutical
  • Cellliar locations

  • Membrane
  • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point198 °CNot Available Boiling PointNot AvailableNot Available Water Solubility7.97e-01 g/LNot Available LogP1.2Not Available

    Predicted Properties

    Property Value Source Water Solubility0.8 mg/mLALOGPS logP2.13ALOGPS logP1.96ChemAxon logS-2.6ALOGPS pKa (Strongest Acidic)18ChemAxon pKa (Strongest Basic)8.61ChemAxon Physiological Charge1ChemAxon Hydrogen Acceptor Count4ChemAxon Hydrogen Donor Count0ChemAxon Polar Surface Area38.77 Å2ChemAxon Rotatable Bond Count1ChemAxon Refractivity82.74 m3·mol-1ChemAxon Polarizability32.05 Å3ChemAxon Number of Rings5ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-0udi-0009000000-f21858df54194757e2d9View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-0udi-0009000000-9b129b5d29df52345272View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-0udi-0649000000-82623b23b75f0a0b232dView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-0002-0920000000-b67ff5a32d0ddd40c4c7View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-006t-0900000000-0277ba7435a4081ab333View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-0g6v-0900000000-b335c52fad1274cd28cbView in MoNA Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available MS

    Mass Spectrum (Electron Ionization)splash10-0005-6970000000-3ba3e105098639cd6091View in MoNA

    Biological Properties Cellliar Locations

  • Membrane
  • Biofluid Locations

  • Blood
  • Urine
  • Tissue Location

    Not Available Pathways

    Name SMPDB Link KEGG Link Hydrocodone PathwaySMP00411Not Available

    Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00956

  • 21059682
  • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00956

  • 21059682
  • details

    Abnormal Concentrations

    Not Available Predicted Concentrations

    Biofluid Value Original age Original sex Original condition Comments Blood0-0.3 uMAdlit (>18 years old)BothNormalPredicted based on drug qualities Blood0-0.2 umol/mmol creatinineAdlit (>18 years old)BothNormalPredicted based on drug qualities

    Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB00956 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    4447623 KEGG Compound ID

    C08024 BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Hydrocodone NuGOwiki Link

    HMDB15091 Metagene Link

    HMDB15091 METLIN ID

    Not Available PubChem Compound

    5284569 PDB ID

    Not Available ChEBI ID

    5779

    Product: Aurothioglucose

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References Not Available

    Enzymes

    General function:
    Involved in monooxygenase 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 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. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
    Gene Name:
    CYP3A4
    Uniprot ID:
    P08684
    Molecular weight:
    57255.585
    References
    1. Hutchinson MR, Menelaou A, Foster DJ, Coller JK, Somogyi AA: CYP2D6 and CYP3A4 involvement in the primary oxidative metabolism of hydrocodone by human liver microsomes. Br J Clin Pharmacol. 2004 Mar;57(3):287-97. [PubMed:14998425 ]
    General function:
    Involved in monooxygenase 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 antidepressants.
    Gene Name:
    CYP2D6
    Uniprot ID:
    P10635
    Molecular weight:
    55768.94
    References
    1. Hutchinson MR, Menelaou A, Foster DJ, Coller JK, Somogyi AA: CYP2D6 and CYP3A4 involvement in the primary oxidative metabolism of hydrocodone by human liver microsomes. Br J Clin Pharmacol. 2004 Mar;57(3):287-97. [PubMed:14998425 ]
    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 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    Specific function:
    Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Highly stereoselective. receptor for enkephalins
    Gene Name:
    OPRD1
    Uniprot ID:
    P41143
    Molecular weight:
    40412.3
    References
    1. Peckham EM, Traynor JR: Comparison of the antinociceptive response to morphine and morphine-like compounds in male and female Sprague-Dawley rats. J Pharmacol Exp Ther. 2006 Mar;316(3):1195-201. Epub 2005 Nov 16. [PubMed:16291875 ]
    2. Thompson CM, Wojno H, Greiner E, May EL, Rice KC, Selley DE: Activation of G-proteins by morphine and codeine congeners: insights to the relevance of O- and N-demethylated metabolites at mu- and delta-opioid receptors. J Pharmacol Exp Ther. 2004 Feb;308(2):547-54. Epub 2003 Nov 4. [PubMed:14600248 ]
    3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    Specific function:
    Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for beta-endorphin
    Gene Name:
    OPRM1
    Uniprot ID:
    P35372
    Molecular weight:
    44778.9
    References
    1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
    2. Kotzer CJ, Hay DW, Dondio G, Giardina G, Petrillo P, Underwood DC: The antitussive activity of delta-opioid receptor stimulation in guinea pigs. J Pharmacol Exp Ther. 2000 Feb;292(2):803-9. [PubMed:10640321 ]
    3. Peckham EM, Traynor JR: Comparison of the antinociceptive response to morphine and morphine-like compounds in male and female Sprague-Dawley rats. J Pharmacol Exp Ther. 2006 Mar;316(3):1195-201. Epub 2005 Nov 16. [PubMed:16291875 ]
    4. Hennies HH, Friderichs E, Schneider J: Receptor binding, analgesic and antitussive potency of tramadol and other selected opioids. Arzneimittelforschung. 1988 Jul;38(7):877-80. [PubMed:2849950 ]
    5. Thompson CM, Wojno H, Greiner E, May EL, Rice KC, Selley DE: Activation of G-proteins by morphine and codeine congeners: insights to the relevance of O- and N-demethylated metabolites at mu- and delta-opioid receptors. J Pharmacol Exp Ther. 2004 Feb;308(2):547-54. Epub 2003 Nov 4. [PubMed:14600248 ]
    6. Stoops WW, Hatton KW, Lofwall MR, Nuzzo PA, Walsh SL: Intravenous oxycodone, hydrocodone, and morphine in recreational opioid users: abuse potential and relative potencies. Psychopharmacology (Berl). 2010 Oct;212(2):193-203. doi: 10.1007/s00213-010-1942-4. Epub 2010 Jul 28. [PubMed:20665209 ]
    7. Walsh SL, Nuzzo PA, Lofwall MR, Holtman JR Jr: The relative abuse liability of oral oxycodone, hydrocodone and hydromorphone assessed in prescription opioid abusers. Drug Alcohol Depend. 2008 Dec 1;98(3):191-202. doi: 10.1016/j.drugalcdep.2008.05.007. Epub 2008 Jul 7. [PubMed:18606504 ]

    PMID: 15211590