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Record Information
Version2.0
Creation Date2009-07-21 20:26:35 UTC
Update Date2014-12-24 20:25:51 UTC
Accession NumberT3D2749
Identification
Common NameCodeine
ClassSmall Molecule
DescriptionIn the United States, codeine is regulated by the Controlled Substances Act. It is a Schedule II controlled substance for pain-relief products containing codeine alone. In combination with aspirin or acetaminophen (paracetamol/tylenol) it is listed as Schedule III. Codeine is also available outside the United States as an over-the-counter drug (Schedule V) in liquid cough-relief formulations. Internationally, codeine is a Schedule II drug under the Single Convention on Narcotic Drugs. In the United Kingdom, codeine is regulated by the Misuse of Drugs Act 1971; it is a Class B Drug, except for concentrations of less than 8mg when combined with paracetamol - or 12.5mg when combined with ibuprofen - which are available in many over the counter preparations. it is a Class B Drug, except for concentrations of less than 8mg when combined with paracetamol - or 12.5mg when combined with ibuprofen - which are available in many over the counter preparations. An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. Codeine or methylmorphine is an opiate used for its analgesic, antitussive and antidiarrheal properties. It is marketed as the salts codeine sulfate and codeine phosphate. Codeine hydrochloride is more commonly marketed in contintental Europe and other regions. Codeine is an alkaloid found in opium in concentrations ranging from 0.3 to 3.0 percent. While codeine can be extracted from opium, most codeine is synthesized from morphine through the process of O-methylation. In the United Kingdom, codeine is regulated by the Misuse of Drugs Act 1971; Codeine or methylmorphine is an opiate used for its analgesic, antitussive and antidiarrheal properties. It is marketed as the salts codeine sulfate and codeine phosphate. Codeine hydrochloride is more commonly marketed in contintental Europe and other regions. Codeine is an alkaloid found in opium in concentrations ranging from 0.3 to 3.0 percent. While codeine can be extracted from opium, most codeine is synthesized from morphine through the process of O-methylation. Theoretically, a dose of approximately 200 mg (oral) of codeine must be administered to give equivalent analgesia to 30 mg (oral) of morphine (Rossi, 2004). It is not used, however, in single doses of greater than 60mg (and no more than 240 mg in 24 hours) since there is a ceiling effect. [PubChem]Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators 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 also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Codeine's analgesic activity is, most likely, due to its conversion to morphine. 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.
Compound Type
  • Amine
  • Analgesic
  • Analgesic, Opioid
  • Antitussive Agent
  • Drug
  • Ether
  • Food Toxin
  • Metabolite
  • Narcotic
  • Opiate Agonist
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(-)-Codeine
(5alpha,6alpha)-7,8-Didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol
(5α,6α)-7,8-didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol
3-Methylmorphin
3-methylmorphine
7,8-Didehydro-4,5alpha-epoxy-3-methoxy-17-methylmorphinan-6alpha-ol
Actacode
Bisoltus
Bromophar
Bronchicum
Bronchodine
Codant
Codedrill
Codein
Codeína
Codeine anhydrous
Codeinum
Codeisan
Coderpina
Codicalm
Codicept
Codinex
Coducept
Cougel
Coutan
Dinco
Farmacod
Galcodine
L-Codeine
Methylmorphine
Morphine 3-methyl ether
Morphine monomethyl ether
morphine-3-methyl ether
Norcodeine, N-Methyl
Norcodine, N-Methyl
O(3)-Methylmorphine
O3-Methylmorphine
Pectoral
Tussoret
Chemical FormulaC18H21NO3
Average Molecular Mass299.364 g/mol
Monoisotopic Mass299.152 g/mol
CAS Registry Number76-57-3
IUPAC Name(1S,5R,13R,14S,17R)-10-methoxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7(18),8,10,15-tetraen-14-ol
Traditional Name(1S,5R,13R,14S,17R)-10-methoxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7(18),8,10,15-tetraen-14-ol
SMILES[H][C@@]12OC3=C(OC)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1([H])C=C[C@]2([H])O
InChI IdentifierInChI=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/h3-6,11-13,17,20H,7-9H2,1-2H3/t11-,12+,13-,17-,18-/m0/s1
InChI KeyInChIKey=OROGSEYTTFOCAN-DNJOTXNNSA-N
Chemical Taxonomy
Description 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.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassMorphinans
Sub ClassNot Available
Direct ParentMorphinans
Alternative Parents
Substituents
  • Morphinan
  • Phenanthrene
  • Tetralin
  • Coumaran
  • Anisole
  • Aralkylamine
  • Alkyl aryl ether
  • Benzenoid
  • Piperidine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary alcohol
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Hair
  • Skin
Pathways
NameSMPDB LinkKEGG Link
Codeine PathwayNot AvailableNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point157.5°C
Boiling Point250°C at 2.20E+01 mm Hg
Solubility9000 mg/L (at 20°C)
LogP1.19
Predicted Properties
PropertyValueSource
Water Solubility0.58 g/LALOGPS
logP1.2ALOGPS
logP1.34ChemAxon
logS-2.7ALOGPS
pKa (Strongest Acidic)13.78ChemAxon
pKa (Strongest Basic)9.19ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area41.93 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity84.6 m³·mol⁻¹ChemAxon
Polarizability31.95 ųChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00lr-3090000000-38668348c3e45e16a9e7JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-0ab9-9135000000-5476697a08758d9606baJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL Thermo Scientific) 60V, Positivesplash10-0uxr-0973000000-87d07ddd2ed24b9598d7JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0udi-0009000000-d68b67071bf467a42afaJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0udi-0009000000-a298cedb776a11677cf7JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0udi-0459000000-1a92521b38ba51a7fa81JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0gc1-0940000000-68cae285315cfe9c7d0eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0uxs-0910000000-b0c288c76c616e1a54d3JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0159-0390000000-ac30542a576060b3373cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0udi-0009000000-870de7833257cd342810JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0udi-0009000000-8ece718ed46e5e439112JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0udi-0139000000-7880499a47dbd2f41229JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0uxr-0973000000-87d07ddd2ed24b9598d7JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-015a-0920000000-4f676c9e2b42320493afJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0uxr-0910000000-e67964930533268605cdJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0udi-0009000000-99b083bf48ae39e3cec6JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0udi-0009000000-efebfbff05a4cb72fe32JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0udi-0139000000-be0f9b6eaa028b54ad6cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0uxr-0973000000-89bc81638a52beefd890JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-015a-0920000000-7eccc8e19d8d88b18128JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0uxr-0910000000-5809a9ed32210bcfa231JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0159-0390000000-a7469c01c0a4ff4179bfJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0uyi-1952000000-3db61b1a0c8cde5b8c82JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0lea-1940000000-b491506c23f09adaee8cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0lea-1930000000-48dcc53ac80bf97d1f2dJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0090000000-d34a35c4caed20d97ad0JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-0090000000-16ee1c88e7d182e8ebf4JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-01ot-3950000000-e80ecb11646b4da6aa92JSpectraViewer | MoNA
Toxicity Profile
Route of ExposureOral, Intramuscular. Well absorbed following oral administration with a bioavailability of approximately 90%. Maximum plasma concentration occurs 60 minutes post-administration. Food does not effect the rate or extent of absorption of codeine.
Mechanism of ToxicityOpiate receptors are coupled with G-protein receptors and function as both positive and negative regulators 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 also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Codeine's analgesic activity is, most likely, due to its conversion to morphine. 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.
MetabolismHepatic. Codeine is a prodrug, itself inactive, but demethylated to the active morphine by the liver enzyme CYP2D6 to morphine. 70-80% of the dose undergoes glucuronidation to form codeine-6-glucuronide. This process is mediated by UDP-glucuronosyltransferase UGT2B7 and UGT2B4. 5-10% of the dose undergoes O-demethylation to morphine and 10% undergoes N-demethylation to form norcodeine. CYP2D6 mediates the biotransformation to morphine. CYP3A4 is the enzymes that mediates the conversion to norcodiene. Morphine and norcodeine are further metabolized and undergo glucuronidation. The glucuronide metabolites of morphine are morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). Both morphine and morphine-6-glucuronide are active and have analgesic activity. Norcodiene and M3G do not have any analgesic properties. Route of Elimination: 90% of the total dose of codeine is excreted through the kidneys, of which 10% is unchanged codeine. Half Life: Plasma half-lives of codeine and its metabolites have been reported to be approximately 3 hours.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor treatment and management of pain (systemic). It is also used as an antidiarrheal and as a cough suppressant.
Minimum Risk LevelNot Available
Health EffectsMedical problems can include congested lungs, liver disease, tetanus, infection of the heart valves, skin abscesses, anemia and pneumonia. Death can occur from overdose.
SymptomsRespiratory depression, sedation and miosis and common symptoms of overdose. Other symptoms include nausea, vomiting, skeletal muscle flaccidity, bradycardia, hypotension, and cool, clammy skin. Apnea and death may ensue.
TreatmentNaloxone antagonizes most effects of codeine. Protect the airway as Naloxone may induce vomiting. Naloxone has a shorter duration of action than codeine; repeated doses may be needed. Protect the patient's airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient's vital signs, blood gases, serum electrolytes, etc. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient's airway when employing gastric emptying or charcoal. (25)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00318
HMDB IDHMDB04995
PubChem Compound ID5284371
ChEMBL IDCHEMBL485
ChemSpider ID4447447
KEGG IDC06174
UniProt IDNot Available
OMIM ID124030 , 608902
ChEBI ID16714
BioCyc IDCODEINE
CTD IDNot Available
Stitch IDCodeine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkCodeine
References
Synthesis Reference

Nagaraj R. Ayyangar, Anil R. Choudhary, Uttam R. Kalkote, Vasant K. Sharma, “Process for the preparation of codeine from morphine.” U.S. Patent US4764615, issued May, 1912.

MSDSLink
General References
  1. Schroeder K, Fahey T: Over-the-counter medications for acute cough in children and adults in ambulatory settings. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD001831. [15495019 ]
  2. Vree TB, van Dongen RT, Koopman-Kimenai PM: Codeine analgesia is due to codeine-6-glucuronide, not morphine. Int J Clin Pract. 2000 Jul-Aug;54(6):395-8. [11092114 ]
  3. Srinivasan V, Wielbo D, Tebbett IR: Analgesic effects of codeine-6-glucuronide after intravenous administration. Eur J Pain. 1997;1(3):185-90. [15102399 ]
  4. Wilkins DG, Haughey HM, Krueger GG, Rollins DE: Disposition of codeine in female human hair after multiple-dose administration. J Anal Toxicol. 1995 Oct;19(6):492-8. [8926744 ]
  5. Ammon S, von Richter O, Hofmann U, Thon KP, Eichelbaum M, Mikus G: In vitro interaction of codeine and diclofenac. Drug Metab Dispos. 2000 Oct;28(10):1149-52. [10997932 ]
  6. Ropero-Miller JD, Lambing MK, Winecker RE: Simultaneous quantitation of opioids in blood by GC-EI-MS analysis following deproteination, detautomerization of keto analytes, solid-phase extraction, and trimethylsilyl derivatization. J Anal Toxicol. 2002 Oct;26(7):524-8. [12423011 ]
  7. Joseph RE Jr, Hold KM, Wilkins DG, Rollins DE, Cone EJ: Drug testing with alternative matrices II. Mechanisms of cocaine and codeine deposition in hair. J Anal Toxicol. 1999 Oct;23(6):396-408. [10517543 ]
  8. Paul BD, Shimomura ET, Smith ML: A practical approach to determine cutoff concentrations for opiate testing with simultaneous detection of codeine, morphine, and 6-acetylmorphine in urine. Clin Chem. 1999 Apr;45(4):510-9. [10102911 ]
  9. Skopp G, Potsch L, Moeller MR: On cosmetically treated hair--aspects and pitfalls of interpretation. Forensic Sci Int. 1997 Jan 17;84(1-3):43-52. [9042709 ]
  10. Piekoszewski W, Janowska E, Stanaszek R, Pach J, Winnik L, Karakiewicz B, Kozielec T: Determination of opiates in serum, saliva and hair addicted persons. Przegl Lek. 2001;58(4):287-9. [11450354 ]
  11. Hebden JM, Gilchrist PJ, Perkins AC, Wilson CG, Spiller RC: Stool water content and colonic drug absorption: contrasting effects of lactulose and codeine. Pharm Res. 1999 Aug;16(8):1254-9. [10468028 ]
  12. Huestis MA, Oyler JM, Cone EJ, Wstadik AT, Schoendorfer D, Joseph RE Jr: Sweat testing for cocaine, codeine and metabolites by gas chromatography-mass spectrometry. J Chromatogr B Biomed Sci Appl. 1999 Oct 15;733(1-2):247-64. [10572984 ]
  13. Sindrup SH, Hofmann U, Asmussen J, Mikus G, Brosen K, Nielsen F, Ingwersen SH, Broen Christensen C: Impact of quinidine on plasma and cerebrospinal fluid concentrations of codeine and morphine after codeine intake. Eur J Clin Pharmacol. 1996;49(6):503-9. [8706777 ]
  14. Klein G, Barkworth MF, Birkenfeld A, Dyde CJ, Rehm KD, Toberich H, Cierpka H: [Relative bioavailability of paracetamol from tablets and suppositories as well as of paracetamol and codeine in a combination tablet]. Arzneimittelforschung. 1986 Mar;36(3):496-9. [3518729 ]
  15. O'Neal CL, Crouch DJ, Rollins DE, Fatah A, Cheever ML: Correlation of saliva codeine concentrations with plasma concentrations after oral codeine administration. J Anal Toxicol. 1999 Oct;23(6):452-9. [10517550 ]
  16. Hill V, Cairns T, Cheng CC, Schaffer M: Multiple aspects of hair analysis for opiates: methodology, clinical and workplace populations, codeine, and poppy seed ingestion. J Anal Toxicol. 2005 Oct;29(7):696-703. [16419403 ]
  17. Yue QY, Hasselstrom J, Svensson JO, Sawe J: Effect of codeine on oro-cecal transit time in Chinese healthy volunteers in comparison with Caucasian subjects. Eur J Clin Pharmacol. 1999 Jan;54(11):839-42. [10027657 ]
  18. Jonasson U, Jonasson B, Saldeen T, Thuen F: The prevalence of analgesics containing dextropropoxyphene or codeine in individuals suspected of driving under the influence of drugs. Forensic Sci Int. 2000 Aug 14;112(2-3):163-9. [10940601 ]
  19. Kintz P, Tracqui A, Mangin P: Analysis of opiates in fly larvae sampled on a putrefied cadaver. J Forensic Sci Soc. 1994 Apr-Jun;34(2):95-7. [8035160 ]
  20. Hofmann U, Seefried S, Schweizer E, Ebner T, Mikus G, Eichelbaum M: Highly sensitive gas chromatographic-tandem mass spectrometric method for the determination of morphine and codeine in serum and urine in the femtomolar range. J Chromatogr B Biomed Sci Appl. 1999 Apr 30;727(1-2):81-8. [10360425 ]
  21. Hepler BR, Sutheimer C, Sunshine I, Sebrosky GF: Combined enzyme immunoassay-LCEC method for the identification, confirmation, and quantitation of opiates in biological fluids. J Anal Toxicol. 1984 Mar-Apr;8(2):78-90. [6371380 ]
  22. Joseph RE Jr, Oyler JM, Wstadik AT, Ohuoha C, Cone EJ: Drug testing with alternative matrices I. Pharmacological effects and disposition of cocaine and codeine in plasma, sebum, and stratum corneum. J Anal Toxicol. 1998 Jan-Feb;22(1):6-17. [9491963 ]
  23. Pascual JA, Sanagustin J: Fully automated analytical method for codeine quantification in human plasma using on-line solid-phase extraction and high-performance liquid chromatography with ultraviolet detection. J Chromatogr B Biomed Sci Appl. 1999 Mar 19;724(2):295-302. [10219671 ]
  24. Drugs.com [Link]
  25. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Opioid receptor activity
Specific Function:
G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine.
Gene Name:
OPRD1
Uniprot ID:
P41143
Molecular Weight:
40368.235 Da
References
  1. Ortiz MI, Castro-Olguin J, Pena-Samaniego N, Castaneda-Hernandez G: Probable activation of the opioid receptor-nitric oxide-cyclic GMP-K+ channels pathway by codeine. Pharmacol Biochem Behav. 2005 Dec;82(4):695-703. Epub 2006 Jan 4. [16386786 ]
  2. Mignat C, Wille U, Ziegler A: Affinity profiles of morphine, codeine, dihydrocodeine and their glucuronides at opioid receptor subtypes. Life Sci. 1995;56(10):793-9. [7885194 ]
  3. Loghin F, Popa DS, Socaciu C: Influence of glutethimide on rat brain mononucleotides by sub-chronic codeine treatment. J Cell Mol Med. 2001 Oct-Dec;5(4):409-16. [12067475 ]
  4. Advenier C, Girard V, Naline E, Vilain P, Emonds-Alt X: Antitussive effect of SR 48968, a non-peptide tachykinin NK2 receptor antagonist. Eur J Pharmacol. 1993 Nov 30;250(1):169-71. [8119316 ]
  5. Karlsson JA, Lanner AS, Persson CG: Airway opioid receptors mediate inhibition of cough and reflex bronchoconstriction in guinea pigs. J Pharmacol Exp Ther. 1990 Feb;252(2):863-8. [2156065 ]
General Function:
Voltage-gated calcium channel activity
Specific Function:
Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors. The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extend to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B. Also couples to adenylate cyclase stimulatory G alpha proteins. The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization. Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction. The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins. The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation. Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling. Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling. Endogenous ligands induce rapid desensitization, endocytosis and recycling whereas morphine induces only low desensitization and endocytosis. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 12 couples to GNAS and is proposed to be involved in excitatory effects. Isoform 16 and isoform 17 do not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity.
Gene Name:
OPRM1
Uniprot ID:
P35372
Molecular Weight:
44778.855 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.105 uMNot AvailableBindingDB 50019351
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Grond S, Sablotzki A: Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879-923. [15509185 ]
  3. Takahama K, Shirasaki T: Central and peripheral mechanisms of narcotic antitussives: codeine-sensitive and -resistant coughs. Cough. 2007 Jul 9;3:8. [17620111 ]
  4. Freissmuth M, Beindl W, Kratzel M: Binding and structure-activity-relation of benzo[f]isoquinoline- and norcodeinone-derivatives at mu-opioid receptors in the rat cerebral cortex. Br J Pharmacol. 1993 Dec;110(4):1429-36. [8306082 ]
  5. Hanessian S, Parthasarathy S, Mauduit M, Payza K: The power of visual imagery in drug design. Isopavines as a new class of morphinomimetics and their human opioid receptor binding activity. J Med Chem. 2003 Jan 2;46(1):34-48. [12502358 ]
General Function:
Opioid receptor activity
Specific Function:
G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions.
Gene Name:
OPRK1
Uniprot ID:
P41145
Molecular Weight:
42644.665 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5015 uMNot AvailableBindingDB 50019351
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Hanessian S, Parthasarathy S, Mauduit M, Payza K: The power of visual imagery in drug design. Isopavines as a new class of morphinomimetics and their human opioid receptor binding activity. J Med Chem. 2003 Jan 2;46(1):34-48. [12502358 ]
General Function:
Steroid hydroxylase 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 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50104 uMNot AvailableBindingDB 50019351
References
  1. Venhorst J, ter Laak AM, Commandeur JN, Funae Y, Hiroi T, Vermeulen NP: Homology modeling of rat and human cytochrome P450 2D (CYP2D) isoforms and computational rationalization of experimental ligand-binding specificities. J Med Chem. 2003 Jan 2;46(1):74-86. [12502361 ]
General Function:
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function:
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoforms USO have no channel activity by themself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.
Gene Name:
KCNH2
Uniprot ID:
Q12809
Molecular Weight:
126653.52 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50301.99517 uMNot AvailableBindingDB 50019351
References
  1. Tobita M, Nishikawa T, Nagashima R: A discriminant model constructed by the support vector machine method for HERG potassium channel inhibitors. Bioorg Med Chem Lett. 2005 Jun 2;15(11):2886-90. [15911273 ]