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Identification
NameHydrocodone
Accession NumberDB00956  (APRD00591)
Typesmall molecule
Groupsapproved, illicit
Description

Narcotic analgesic related to codeine, but more potent and more addicting by weight. It is used also as cough suppressant. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
DihydrocodeinoneNot AvailableNot Available
HidrocodonaSpanishINN
HydrocodonNot AvailableNot Available
HydrocodonumLatinINN
HydroconeNot AvailableNot Available
HydroconumNot AvailableNot Available
IdrocodoneNot AvailableDCIT
SaltsNot Available
Brand names
NameCompany
ReprexainNot Available
ZohydroNot Available
Brand mixtures
Brand NameIngredients
Caldomine DHHydrocodone Bitartrate + Pheniramine Maleate + Phenylpropanolamine Hydrochloride + Pyrilamine Maleate
Coristine-DHHydrocodone Bitartrate + Phenylephrine Hydrochloride
DalmacolAlcohol Anhydrous + Doxylamine Succinate + Etafedrin Hydrochloride + Hydrocodone Bitartrate + Sodium Citrate
Dimetane Expectorant-DCBrompheniramine Maleate + Guaifenesin + Hydrocodone Bitartrate + Phenylephrine Hydrochloride + Phenylpropanolamine Hydrochloride
HycetAcetaminophen + Hydrocodone
Hycomine-SAmmonium Chloride + Hydrocodone Bitartrate + Phenylephrine Hydrochloride + Pyrilamine Maleate
IBUDONEHydrocodone + Ibuprofen
MaxidoneAcetaminophen + Hydrocodone
Mercodol with DecaprynDoxylamine Succinate + Etafedrin Hydrochloride + Hydrocodone Bitartrate + Sodium Citrate
NorcoHydrocodone + Ibuprofen
NORCOHydrocodone + Ibuprofen
Novahistex DGGuaifenesin + Hydrocodone Bitartrate + Phenylephrine Hydrochloride
Novahistex DHHydrocodone Bitartrate + Phenylephrine Hydrochloride
Ratio-CalmydoneDoxylamine Succinate + Etafedrin Hydrochloride + Hydrocodone Bitartrate + Sodium Citrate
Ratio-Coristex-DHHydrocodone Bitartrate + Phenylephrine Hydrochloride
REPREXAINHydrocodone + Ibuprofen
REZIRAHydrocodone + Ibuprofen
Solucodan SyrupHydrocodone Bitartrate + Menthol + Potassium Guaiacol Sulphonate + Sodium Citrate
Solucodan-HDiphenylpyraline Hydrochloride + Hydrocodone Bitartrate + Menthol + Potassium Guaiacol Sulphonate + Sodium Citrate
Triaminic Expectorant DH SyrupGuaifenesin + Hydrocodone Bitartrate + Pheniramine Maleate + Phenylpropanolamine Hydrochloride + Pyrilamine Maleate
Tussaminic DHHydrocodone Bitartrate + Pheniramine Maleate + Phenylpropanolamine Hydrochloride + Pyrilamine Maleate
TussiCapsHydrocodone + Chlorphenamine
TUSSICAPSHydrocodone + Ibuprofen
VituzHydrocodone + Chlorphenamine
XodolAcetaminophen + Hydrocodone
ZAMICETAcetaminophen + Hydrocodone
ZolvitAcetaminophen + Hydrocodone
ZUTRIPROPseudoephedrine + Hydrocodone + Chlorphenamine
Categories
CAS number125-29-1
WeightAverage: 299.3642
Monoisotopic: 299.152143543
Chemical FormulaC18H21NO3
InChI KeyLLPOLZWFYMWNKH-CMKMFDCUSA-N
InChI
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
IUPAC Name
(1S,5R,13R,17R)-10-methoxy-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(OC)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1([H])CCC2=O
Mass Specshow(10.3 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassAlkaloids and Derivatives
ClassMorphinans
SubclassNot Available
Direct parentMorphinans
Alternative parentsBenzylisoquinolines; Phenanthrenes and Derivatives; Isoquinolones and Derivatives; Tetralins; Benzofurans; Anisoles; Cyclohexanones; Alkyl Aryl Ethers; Piperidines; Tertiary Amines; Polyamines
Substituentsphenanthrene; isoquinolone; tetralin; benzofuran; phenol ether; anisole; cyclohexanone; alkyl aryl ether; piperidine; benzene; ketone; tertiary amine; ether; polyamine; amine; organonitrogen compound; carbonyl group
Classification descriptionThis compound belongs to the 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.
Pharmacology
IndicationFor relief of moderate to moderately severe pain. Also used for the symptomatic relief of nonproductive cough, alone or in combination with other antitussives or expectorants.
PharmacodynamicsHydrocodone, a semisynthetic opiate agonist and hydrogenated ketone derivative, is similar to other phenanthrene derivatives, such as codeine. Used as an analgesic, hydrocodone is combined with acetaminophen, ibuprofen, or aspirin to treat pain. Used as an antitussive, hydrocodone is combined with phenylephrine, pseudoephedrine, phenylpropanolamine, guaifenesin, pyrilamine, pheniramine, or chlorpheniramine. Opiate agonists exert their principal pharmacologic effect at specific receptor binding sites in the CNS and other tissues. There are several subtypes of opiate receptors including the mu receptor (localized in pain modulating regions of the CNS), the kappa receptor (localized in the deep layers of the cerebral cortex), the delta receptor (localized in the limbic regions of the CNS), and the sigma receptor (thought to mediate the dysphoric and psychotomimetic effects of some opiate partial agonists). Agonist activity at the mu or kappa receptor can result in analgesia, miosis, and/or decreased body temperature. Agonist activity at the mu receptor can also result in suppression of opiate withdrawal, whereas antagonist activity can result in precipitation of withdrawal. Opiate agonists act at several sites within the CNS involving several systems of neurotransmitters to produce analgesia, but the precise mechanism of action has not been fully determined. Opiate agonists do not alter the threshold or responsiveness of afferent nerve endings to noxious stimuli nor the conduction of impulses along peripheral nerves. Instead, they alter the perception of pain at the spinal cord and higher levels in the CNS and the person's emotional response to pain.
Mechanism of actionHydrocodone 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 modulators, both positive and negative, of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates 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 intracellular 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, insulin, 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 results in hyperpolarization and reduced neuronal excitability.
AbsorptionWell absorbed from the gastrointestinal tract.
Volume of distributionNot Available
Protein bindingAs most agents in the 5-ring morphinan group of semi-synthetic opioids bind plasma protein to a similar degree (range 19% [hydromorphone] to 45% [oxycodone]), hydrocodone is expected to fall within this range.
Metabolism

Hepatic and also in intestinal mucosa.

SubstrateEnzymesProduct
Hydrocodone
hydromorphoneDetails
Hydrocodone
norhydrocodoneDetails
Route of eliminationNot Available
Half life1.25-3 hours
ClearanceNot Available
ToxicitySymptoms of overdose include respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, dizziness, ringing in the ears, confusion, blurred vision, eye problems, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdose, apnea, circulatory collapse, cardiac arrest and death may occur. LD50=85.7mg/kg (subcutaneous, in mice).
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Hydrocodone Action PathwayDrug actionSMP00411
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9984
Caco-2 permeable + 0.8621
P-glycoprotein substrate Substrate 0.8253
P-glycoprotein inhibitor I Inhibitor 0.6425
P-glycoprotein inhibitor II Non-inhibitor 0.8664
Renal organic cation transporter Inhibitor 0.6604
CYP450 2C9 substrate Non-substrate 0.8546
CYP450 2D6 substrate Substrate 0.8997
CYP450 3A4 substrate Substrate 0.8168
CYP450 1A2 substrate Non-inhibitor 0.8207
CYP450 2C9 substrate Non-inhibitor 0.9412
CYP450 2D6 substrate Inhibitor 0.6629
CYP450 2C19 substrate Non-inhibitor 0.8402
CYP450 3A4 substrate Non-inhibitor 0.7625
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8675
Ames test Non AMES toxic 0.7735
Carcinogenicity Non-carcinogens 0.9419
Biodegradation Not ready biodegradable 0.984
Rat acute toxicity 3.0914 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9024
hERG inhibition (predictor II) Non-inhibitor 0.8165
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
SyrupOral
TabletOral
Prices
Unit descriptionCostUnit
Hydrocodone-Acetaminophen 7.5-500 mg/15ml Solution 473ml Bottle60.97USDbottle
Hydrocodone-Ibuprofen 7.5-200 mg tablet1.13USDtablet
Hydrocodone-Acetaminophen 10-750 mg tablet1.1USDtablet
Hydrocodone-Acetaminophen 7.5-325 mg tablet0.63USDtablet
Hydrocodone-Acetaminophen 10-325 mg tablet0.57USDtablet
Hydrocodone-Acetaminophen 5-325 mg tablet0.57USDtablet
Hydrocodone-Acetaminophen 10-660 mg tablet0.53USDtablet
Hydrocodone-Acetaminophen 10-500 mg tablet0.5USDtablet
Hydrocodone-Acetaminophen 10-650 mg tablet0.47USDtablet
Hydrocodone-Acetaminophen 7.5-500 mg tablet0.47USDtablet
Hydrocodone-Acetaminophen 2.5-500 mg tablet0.43USDtablet
Hydrocodone-Acetaminophen 7.5-750 mg tablet0.43USDtablet
Hydrocodone-Acetaminophen 5-500 mg tablet0.4USDtablet
Hydrocodone-Acetaminophen 7.5-650 mg tablet0.16USDtablet
Hydrocodone-Homatropine 5-1.5 mg/5ml Syrup0.15USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point198 °CPhysProp
water solubilityInsolubleNot Available
logP1.2Not Available
Predicted Properties
PropertyValueSource
water solubility7.97e-01 g/lALOGPS
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 area38.77ChemAxon
rotatable bond count1ChemAxon
refractivity82.74ChemAxon
polarizability32.05ChemAxon
number of rings5ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Anne M. Hailes, Christopher E. French, Neil C. Bruce, “Morphinone reductase for the preparation of hydromorphone and hydrocodone.” U.S. Patent US5571685, issued November, 1990.

US5571685
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC08024
PubChem Compound5284569
PubChem Substance46506225
ChemSpider4447623
ChEBI5779
ChEMBLCHEMBL1457
Therapeutic Targets DatabaseDAP000253
PharmGKBPA449900
Drug Product Database1916580
RxListhttp://www.rxlist.com/cgi/generic/hydrocod.htm
WikipediaHydrocodone
ATC CodesR05DA03
AHFS Codes
  • 48:08.00
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(48.8 KB)
Interactions
Drug Interactions
Drug
AlvimopanIncreases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
EltrombopagIncreases levels of Hydrocodone via metabolism decrease. UDP-glucuronosyltransferase inhibition with unclear significance.
TriprolidineThe CNS depressants, Triprolidine and Hydrocodone, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Food Interactions
  • Avoid alcohol.
  • Take with food.
  • To avoid constipation: increase your daily intake of fiber (beans, whole grains, vegetables).

Targets

1. Mu-type opioid receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Mu-type opioid receptor P35372 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  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
  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
  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
  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
  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 Jul 28. Pubmed
  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. Epub 2008 Jul 7. Pubmed

2. Delta-type opioid receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Delta-type opioid receptor P41143 Details

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

Enzymes

1. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

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
  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. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12