Banner
targets (2) enzymes (2)
for drugs
Identification
Name Hydrocodone
Accession Number DB00956 (APRD00591)
Type small molecule
Groups illicit, approved
Description

Narcotic analgesic related to codeine, but more potent and more addicting by weight. It is used also as cough suppressant. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Dihydrocodeinone
Hidrocodona [INN-Spanish]
Hydrocodon
Hydrocodonum [INN-Latin]
Hydrocone
Hydroconum
Idrocodone [Dcit]
Salts Not Available
Brand names
Name Company
Bekadid
Codinovo
Dico
Dicodid
Multacodin
Brand mixtures
Brand Name Ingredients
Caldomine DH Adulte Hydrocodone Bitartrate + Pheniramine Maleate + Phenylpropanolamine Hydrochloride + Pyrilamine Maleate
Caldomine DH Enfant Hydrocodone Bitartrate + Pheniramine Maleate + Phenylpropanolamine Hydrochloride + Pyrilamine Maleate
Coristine-DH Liq Hydrocodone Bitartrate + Phenylephrine Hydrochloride
Dalmacol Alcohol Anhydrous + Doxylamine Succinate + Etafedrin Hydrochloride + Hydrocodone Bitartrate + Sodium Citrate
Dimetane Expectorant-DC Syr Brompheniramine Maleate + Guaifenesin + Hydrocodone Bitartrate + Phenylephrine Hydrochloride + Phenylpropanolamine Hydrochloride
Dimetane Expectorant-DC Syrup Brompheniramine Maleate + Guaifenesin + Hydrocodone Bitartrate + Phenylephrine Hydrochloride
Hycomine-S Ammonium Chloride + Hydrocodone Bitartrate + Phenylephrine Hydrochloride + Pyrilamine Maleate
Mercodol with Decapryn Doxylamine Succinate + Etafedrin Hydrochloride + Hydrocodone Bitartrate + Sodium Citrate
Novahistex Dh Expectorant Guaifenesin + Hydrocodone Bitartrate + Phenylephrine Hydrochloride
Novahistex Dh Syrup Hydrocodone Bitartrate + Phenylephrine Hydrochloride
Ratio-Calmydone Doxylamine Succinate + Etafedrin Hydrochloride + Hydrocodone Bitartrate + Sodium Citrate
Ratio-Coristex-DH Hydrocodone Bitartrate + Phenylephrine Hydrochloride
Solucodan Syrup Hydrocodone Bitartrate + Menthol + Potassium Guaiacol Sulphonate + Sodium Citrate
Solucodan-H Diphenylpyraline Hydrochloride + Hydrocodone Bitartrate + Menthol + Potassium Guaiacol Sulphonate + Sodium Citrate
Triaminic Expectorant DH Syrup Guaifenesin + Hydrocodone Bitartrate + Pheniramine Maleate + Phenylpropanolamine Hydrochloride + Pyrilamine Maleate
Tussaminic DH Forte Syrup Hydrocodone Bitartrate + Pheniramine Maleate + Phenylpropanolamine Hydrochloride + Pyrilamine Maleate
Tussaminic DH Pediatric Syrup Hydrocodone Bitartrate + Pheniramine Maleate + Phenylpropanolamine Hydrochloride + Pyrilamine Maleate
First Prev Next Last
Categories
  • Narcotics
  • Analgesics
  • Antitussives
  • Analgesics, Opioid
  • Antitussive Agents
CAS number 125-29-1
Weight Average: 299.3642
Monoisotopic: 299.152143543
Chemical Formula C18H21NO3
InChI Key InChIKey=LLPOLZWFYMWNKH-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
Plain Text
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
Plain Text
Mass Spec show (10.3 KB)
Taxonomy
Kingdom Organic
Classes
  • Morphinans
  • Benzylisoquinolines
Substructures
  • Morphinans
  • Benzofurans
  • Naphthalenes
  • Phenols and Derivatives
  • Benzylisoquinolines
  • Ethers
  • Benzene and Derivatives
  • Phenylpiperidines
  • Aliphatic and Aryl Amines
  • 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 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.
Pharmacodynamics Hydrocodone, 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 action 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 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.
Absorption Well absorbed from the gastrointestinal tract.
Volume of distribution Not Available
Protein binding As 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.
Route of elimination Not Available
Half life 1.25-3 hours
Clearance Not Available
Toxicity Symptoms 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
Pathway Name SMPDB ID
Smp00411 Hydrocodone Pathway SMP00411
Pharmacoeconomics
Manufacturers Not Available
Packagers
Dosage forms
Form Route Strength
Syrup Oral
Tablet Oral
Prices
Unit description Cost Unit
Hydrocodone-Acetaminophen 7.5-500 mg/15ml Solution 473ml Bottle 60.97 USD bottle
Hydrocodone-Ibuprofen 7.5-200 mg tablet 1.13 USD tablet
Hydrocodone-Acetaminophen 10-750 mg tablet 1.1 USD tablet
Hydrocodone-Acetaminophen 7.5-325 mg tablet 0.63 USD tablet
Hydrocodone-Acetaminophen 10-325 mg tablet 0.57 USD tablet
Hydrocodone-Acetaminophen 5-325 mg tablet 0.57 USD tablet
Hydrocodone-Acetaminophen 10-660 mg tablet 0.53 USD tablet
Hydrocodone-Acetaminophen 10-500 mg tablet 0.5 USD tablet
Hydrocodone-Acetaminophen 10-650 mg tablet 0.47 USD tablet
Hydrocodone-Acetaminophen 7.5-500 mg tablet 0.47 USD tablet
Hydrocodone-Acetaminophen 2.5-500 mg tablet 0.43 USD tablet
Hydrocodone-Acetaminophen 7.5-750 mg tablet 0.43 USD tablet
Hydrocodone-Acetaminophen 5-500 mg tablet 0.4 USD tablet
Hydrocodone-Acetaminophen 7.5-650 mg tablet 0.16 USD tablet
Hydrocodone-Homatropine 5-1.5 mg/5ml Syrup 0.15 USD ml
First Prev Next Last
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 198 °C PhysProp
water solubility Insoluble Not Available
logP 1.2 Not Available
Predicted Properties
Property Value Source
water solubility 7.97e-01 g/l ALOGPS
logP 2.13 ALOGPS
logP 1.96 ChemAxon
logS -2.6 ALOGPS
pKa (strongest acidic) 18 ChemAxon
pKa (strongest basic) 8.61 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 38.77 ChemAxon
rotatable bond count 1 ChemAxon
refractivity 82.74 ChemAxon
polarizability 32.05 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C08024 Link_out
PubChem Compound 5284569 Link_out
PubChem Substance 46506225 Link_out
ChemSpider 4447623 Link_out
ChEBI 5779 Link_out
ChEMBL 5779 Link_out
Therapeutic Targets Database DAP000253 Link_out
PharmGKB PA449900 Link_out
Drug Product Database 1916580 Link_out
RxList http://www.rxlist.com/cgi/generic/hydrocod.htm Link_out
Wikipedia http://en.wikipedia.org/wiki/Hydrocodone Link_out
ATC Codes
  • R05DA03
AHFS Codes
  • 48:08.00
PDB Entries Not Available
FDA label Not Available
MSDS show (48.8 KB)
Interactions
Drug Interactions
Drug Interaction
Alvimopan Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Eltrombopag Increases levels of Hydrocodone via metabolism decrease. UDP-glucuronosyltransferase inhibition with unclear significance.
Triprolidine The 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

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. 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

Pharmacological action: yes
Actions: agonist

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. 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

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. 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

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. 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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19