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Identification
NameMorphine
Accession NumberDB00295  (APRD00215)
Typesmall molecule
Groupsapproved, investigational
Description

The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
(−)-morphineNot AvailableNot Available
MorphinGermanNot Available
MorphinumLatinNot Available
Salts
Name/CAS Structure Properties
Morphine Sulfate
Thumb
  • InChI Key: USAHOPJHPJHUNS-IFCNUISUSA-N
  • Monoisotopic Mass: 668.2403662
  • Average Mass: 668.754
DBSALT000122
Brand names
NameCompany
AvinzaNot Available
KadianNot Available
KapanolNot Available
MS ContinNot Available
MSIRNot Available
OramorphNot Available
RoxanolNot Available
Brand mixtures
Brand NameIngredients
Camphorated Opium TinctureBenzoic Acid + Camphor + Morphine
ParegoriqueCamphor + Morphine
Categories
CAS number57-27-2
WeightAverage: 285.3377
Monoisotopic: 285.136493479
Chemical FormulaC17H19NO3
InChI KeyInChIKey=BQJCRHHNABKAKU-KBQPJGBKSA-N
InChI
InChI=1S/C17H19NO3/c1-18-7-6-17-10-3-5-13(20)16(17)21-15-12(19)4-2-9(14(15)17)8-11(10)18/h2-5,10-11,13,16,19-20H,6-8H2,1H3/t10-,11+,13-,16-,17-/m0/s1
IUPAC Name
(1S,5R,13R,14S,17R)-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7(18),8,10,15-tetraene-10,14-diol
SMILES
[H][C@@]12OC3=C(O)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1([H])C=C[C@@H]2O
Mass Specshow(9.42 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassAlkaloids and Derivatives
ClassMorphinans
SubclassNot Available
Direct parentMorphinans
Alternative parentsBenzylisoquinolines; Phenanthrenes and Derivatives; Tetralins; Benzofurans; Phenols and Derivatives; Alkyl Aryl Ethers; Piperidines; Secondary Alcohols; Tertiary Amines; Polyamines; Enols
Substituentsphenanthrene; tetralin; benzofuran; phenol derivative; alkyl aryl ether; benzene; piperidine; tertiary amine; secondary alcohol; polyamine; enol; ether; amine; alcohol; organonitrogen compound
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 the relief and treatment of severe pain.
PharmacodynamicsMorphine is a narcotic pain management agent indicated for the relief of pain in patients who require opioid analgesics for more than a few days. Morphine 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. In clinical settings, morphine exerts its principal pharmacological effect on the central nervous system and gastrointestinal tract. Its primary actions of therapeutic value are analgesia and sedation. Morphine appears to increase the patient's tolerance for pain and to decrease discomfort, although the presence of the pain itself may still be recognized. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Opioids also produce respiratory depression by direct action on brain stem respiratory centers.
Mechanism of actionThe precise mechanism of the analgesic action of morphine is unknown. However, specific CNS opiate receptors have been identified and likely play a role in the expression of analgesic effects. Morphine first acts on the mu-opioid receptors. The mechanism of respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to increases in carbon dioxide tension and to electrical stimulation. It has been shown that morphine binds to and inhibits GABA inhibitory interneurons. These interneurons normally inhibit the descending pain inhibition pathway. So, without the inhibitory signals, pain modulation can proceed downstream.
AbsorptionBioavailability is approximately 30%.
Volume of distribution
  • 1 to 6 L/kg
Protein binding30-40%
Metabolism

Primarily hepatic (90%), converted to dihydromorphinone and normorphine. Also converted to morphine-3-glucuronide (M3G) and morphine-6-glucuronide. Virtually all morphine is converted to glucuronide metabolites; only a small fraction (less than 5%) of absorbed morphine is demethylated.

SubstrateEnzymesProduct
Morphine
morphine-6-glucuronideDetails
Morphine
morphine-3-glucuronideDetails
Morphine
    NormorphineDetails
    Route of eliminationA small amount of glucuronide conjugates are excreted in bile, with minor enterohepatic recycling. Seven to 10% of administered morphine sulfate is excreted in the feces.
    Half life2-4 hours
    Clearance
    • 20 – 30 mL/min/kg [Adult]
    • 1852 +/- 116 mL/min [Chinese]
    • 1495 +/- 80 mL/min [Caucasian]
    ToxicityLD50 = 461 mg/kg (rat, oral), 600 mg/kg (mouse, oral). Human lethal dose by ingestion is 120-250 mg of morphine sulfate. Symptoms of overdose include cold, clammy skin, flaccid muscles, fluid in the lungs, lowered blood pressure, "pinpoint" or dilated pupils, sleepiness leading to stupor and coma, slowed breathing, and slow pulse rate.
    Affected organisms
    • Humans and other mammals
    Pathways
    PathwayCategorySMPDB ID
    Codeine Action PathwayDrug actionSMP00405
    Morphine Action PathwayDrug actionSMP00406
    Heroin Action PathwayDrug actionSMP00407
    Codeine Metabolism PathwayDrug metabolismSMP00621
    Heroin Metabolism PathwayDrug metabolismSMP00623
    Morphine Metabolism PathwayDrug metabolismSMP00622
    SNP Mediated Effects
    Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeEffectReference(s)
    Multidrug resistance protein 1
    Gene symbol: ABCB1
    UniProt: P08183
    rs1045642 Not AvailableT AlleleBetter response to pain relief drugs17898703
    Mu-type opioid receptor
    Gene symbol: OPRM1
    UniProt: P35372
    rs1799971 Not AvailableA AlleleBetter response to pain relief drugs17898703
    SNP Mediated Adverse Drug ReactionsNot Available
    ADMET
    Predicted ADMET features
    Property Value Probability
    Human Intestinal Absorption + 0.9971
    Blood Brain Barrier + 0.9882
    Caco-2 permeable + 0.8867
    P-glycoprotein substrate Substrate 0.8787
    P-glycoprotein inhibitor I Non-inhibitor 0.8782
    P-glycoprotein inhibitor II Non-inhibitor 0.956
    Renal organic cation transporter Inhibitor 0.6221
    CYP450 2C9 substrate Non-substrate 0.7451
    CYP450 2D6 substrate Substrate 0.8919
    CYP450 3A4 substrate Substrate 0.7375
    CYP450 1A2 substrate Non-inhibitor 0.5191
    CYP450 2C9 substrate Non-inhibitor 0.9046
    CYP450 2D6 substrate Non-inhibitor 0.647
    CYP450 2C19 substrate Non-inhibitor 0.8155
    CYP450 3A4 substrate Non-inhibitor 0.9176
    CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7503
    Ames test Non AMES toxic 0.9132
    Carcinogenicity Non-carcinogens 0.9634
    Biodegradation Not ready biodegradable 0.9944
    Rat acute toxicity 2.8989 LD50, mol/kg Not applicable
    hERG inhibition (predictor I) Weak inhibitor 0.8367
    hERG inhibition (predictor II) Non-inhibitor 0.874
    Pharmacoeconomics
    Manufacturers
    • King pharmaceuticals inc
    • Actavis elizabeth llc
    • Ekr therapeutics inc
    • App pharmaceuticals llc
    • Baxter healthcare corp anesthesia and critical care
    • Hospira inc
    • Mallinckrodt chemical inc
    • Meridian medical technologies inc
    • Watson laboratories inc
    • Roxane laboratories inc
    • Clonmel healthcare ltd
    • Endo pharmaceuticals inc
    • Kv pharmaceutical co
    • Mallinckrodt inc
    • Purdue pharma lp
    • Xanodyne pharmaceutics inc
    • Actavis
    Packagers
    Dosage forms
    FormRouteStrength
    Capsule, extended releaseOral
    LiquidIntramuscular
    LiquidIntravenous
    SoapTopical
    SolutionEpidural
    SolutionIntramuscular
    SolutionIntravenous
    Solution / dropsOral
    SuppositoryRectal
    SyrupOral
    TabletOral
    Tablet, extended releaseOral
    Prices
    Unit descriptionCostUnit
    Depodur 15 mg/1.5 ml vial618.18USDml
    Roxanol 20 mg/ml Solution 120ml Bottle95.98USDbottle
    Morphine Sulfate 20 mg/5ml Solution 500ml Bottle65.05USDbottle
    Apokyn 30 mg/3 ml cartridge52.48USDml
    Morphine Sulfate 10 mg/5ml Solution 500ml Bottle38.55USDbottle
    Kadian er 200 mg capsule35.43USDcapsule
    Kadian er 100 mg capsule23.01USDcapsule
    Roxanol 20 mg/ml Solution 30ml Bottle22.99USDbottle
    Morphine Sulfate 10 mg/5ml Solution 100ml Bottle21.99USDbottle
    Oramorph sr 60 mg tablet21.76USDtablet
    Ms contin 200 mg tablet21.5USDtablet
    Kadian er 80 mg capsule18.66USDcapsule
    Roxanol 20 mg/ml Solution 240ml Bottle17.99USDbottle
    Avinza 90 mg capsule17.56USDcapsule
    Oramorph sr 100 mg tablet17.16USDtablet
    Kadian 100 mg 24 Hour Capsule16.93USDcapsule
    MS Contin 200 mg 12 Hour tablet16.32USDtablet
    Kadian 100 mg capsule sr16.25USDcapsule
    Kadian er 60 mg capsule14.31USDcapsule
    AVINza 90 mg 24 Hour Capsule13.21USDcapsule
    Kadian 80 mg capsule sr12.96USDcapsule
    Avinza 120 mg capsule12.07USDcapsule
    Kadian er 50 mg capsule11.76USDcapsule
    Ms contin 100 mg tablet11.75USDtablet
    Avinza 60 mg capsule11.58USDcapsule
    AVINza 120 mg 24 Hour Capsule11.33USDcapsule
    Avinza 75 mg capsule10.79USDcapsule
    Morphine sulfate powder10.61USDg
    Avinza 45 mg capsule10.22USDcapsule
    Kadian 60 mg 24 Hour Capsule9.06USDcapsule
    Morphine Sulfate CR 200 mg 12 Hour tablet8.97USDtablet
    MS Contin 100 mg 12 Hour tablet8.89USDtablet
    Morphine sulf 30 mg suppository8.44USDsuppository
    AVINza 60 mg 24 Hour Capsule8.36USDcapsule
    Ms contin 60 mg tablet7.95USDtablet
    Infumorph 10 mg/ml ampul p-f7.8USDml
    Kadian 50 mg 24 Hour Capsule7.71USDcapsule
    Kadian er 30 mg capsule7.13USDcapsule
    Oramorph sr 30 mg tablet6.83USDtablet
    Morphine sulf 20 mg suppository6.71USDsuppository
    Kadian er 10 mg capsule6.35USDcapsule
    Morphine sulf 10 mg suppository6.25USDsuppository
    Avinza 30 mg capsule6.0USDcapsule
    MS Contin 60 mg 12 Hour tablet5.71USDtablet
    Kadian er 20 mg capsule5.69USDcapsule
    Ms Contin 200 mg Sustained-Release Tablet5.62USDtablet
    Kadian 30 mg 24 Hour Capsule4.8USDcapsule
    Kadian 20 mg 24 Hour Capsule4.76USDcapsule
    AVINza 30 mg 24 Hour Capsule4.47USDcapsule
    Morphine sulf 5 mg suppository4.45USDsuppository
    Morphine Sulfate CR 100 mg 12 Hour tablet4.33USDtablet
    M-Eslon 200 mg Extended-Release Capsule4.3USDcapsule
    Oramorph sr 15 mg tablet4.12USDtablet
    Ms contin cr 30 mg tablet4.09USDtablet
    Kadian 10 mg capsule sr4.05USDcapsule
    Morphine Hp 50 50 mg/ml4.01USDml
    Kadian 10 mg 24 Hour Capsule4.0USDcapsule
    Ms contin 15 mg tablet3.58USDtablet
    MS Contin 30 mg 12 Hour tablet3.26USDtablet
    Novo-Morphine Sr 200 mg Sustained-Release Tablet3.09USDtablet
    Pms-Morphine Sulfate Sr 200 mg Sustained-Release Tablet3.09USDtablet
    Ms Contin 100 mg Sustained-Release Tablet3.02USDtablet
    Morphine Sulfate CR 60 mg 12 Hour tablet3.0USDtablet
    Morphine Hp 25 25 mg/ml2.9USDml
    Statex 30 mg Suppository2.55USDsuppository
    Kadian 100 mg Sustained-Release Capsule2.35USDcapsule
    Statex 20 mg Suppository2.32USDsuppository
    Morphine Lp Epidural 1 mg/ml2.24USDml
    M-Eslon 100 mg Extended-Release Capsule2.15USDcapsule
    MS Contin 15 mg 12 Hour tablet2.13USDtablet
    Ms Contin 60 mg Sustained-Release Tablet1.98USDtablet
    Statex 10 mg Suppository1.95USDsuppository
    Morph sulf 5 mg/0.25 ml vial1.83USDvial
    Statex 5 mg Suppository1.75USDsuppository
    Novo-Morphine Sr 100 mg Sustained-Release Tablet1.66USDtablet
    Pms-Morphine Sulfate Sr 100 mg Sustained-Release Tablet1.66USDtablet
    Morphine Sulfate CR 30 mg 12 Hour tablet1.63USDtablet
    Morphine 8 mg/ml ampule1.56USDml
    Kadian 50 mg Sustained-Release Capsule1.35USDcapsule
    Duramorph 0.5 mg/ml ampul1.31USDml
    Astramorph-pf 1 mg/ml ampul1.15USDml
    Ms Contin 30 mg Sustained-Release Tablet1.13USDtablet
    Morphine Lp Epidural 0.5 mg/ml1.12USDml
    Morphine Sulfate 15 mg/ml1.03USDml
    Morphine Sulfate 10 mg/ml1.02USDml
    Novo-Morphine Sr 60 mg Sustained-Release Tablet1.01USDtablet
    Pms-Morphine Sulfate Sr 60 mg Sustained-Release Tablet1.01USDtablet
    Ratio-Morphine Sulfate Sr 60 mg Sustained-Release Tablet1.01USDtablet
    M-Eslon 60 mg Extended-Release Capsule1.0USDcapsule
    Statex 50 mg/ml Drops0.99USDml
    Morphine Sulfate CR 15 mg 12 Hour tablet0.93USDtablet
    Duramorph 1 mg/ml ampul0.91USDml
    M.O.S.-Sr 60 mg Sustained-Release Tablet0.89USDtablet
    Morphine 50 mg/25 ml-d5w syr0.86USDml
    Morphine-ns 10 mg/ml syringe0.86USDml
    Morphine-ns 5 mg/ml syringe0.8USDml
    Ms Contin 15 mg Sustained-Release Tablet0.75USDtablet
    Morphine 5 mg/ml vial0.74USDml
    Kadian 20 mg Sustained-Release Capsule0.73USDcapsule
    Astramorph-pf 0.5 mg/ml amp0.72USDml
    Morphine Sulfate 15 mg tablet0.65USDtablet
    Morphine Sulfate 30 mg tablet0.65USDtablet
    Morphine 1 mg/ml vial p-f0.6USDml
    Morphine-ns 1 mg/ml syringe0.58USDml
    Novo-Morphine Sr 30 mg Sustained-Release Tablet0.57USDtablet
    Pms-Morphine Sulfate Sr 30 mg Sustained-Release Tablet0.57USDtablet
    Ratio-Morphine Sulfate Sr 30 mg Sustained-Release Tablet0.57USDtablet
    M-Eslon 30 mg Extended-Release Capsule0.56USDcapsule
    Morphine 0.5 mg/ml vial0.55USDml
    Morphine sulfate 50 mg/ml vial0.55USDml
    Morphine sulfate ir 30 mg tablet0.55USDtablet
    Ratio-Morphine 20 mg/ml Syrup0.55USDsyrup
    Statex 20 mg/ml Drops0.52USDml
    M.O.S.-Sr 30 mg Sustained-Release Tablet0.51USDtablet
    Morphine 1 mg/ml syringe0.48USDml
    Morphine 10 mg/ml vial0.48USDml
    Ms.Ir 30 mg Tablet0.48USDtablet
    Morphine sulfate 25 mg/ml vial0.43USDml
    Morphine sulf 1 mg/ml vial0.4USDml
    M.O.S. Sulfate 50 mg Tablet0.39USDtablet
    Statex 50 mg Tablet0.39USDtablet
    Kadian 10 mg Sustained-Release Capsule0.38USDcapsule
    M-Eslon 15 mg Extended-Release Capsule0.38USDcapsule
    Ms.Ir 20 mg Tablet0.38USDtablet
    Novo-Morphine Sr 15 mg Sustained-Release Tablet0.37USDtablet
    Pms-Morphine Sulfate Sr 15 mg Sustained-Release Tablet0.37USDtablet
    Ratio-Morphine Sulfate Sr 15 mg Sustained-Release Tablet0.37USDtablet
    M-Eslon 10 mg Extended-Release Capsule0.33USDcapsule
    Morphine sulfate ir 15 mg tablet0.32USDtablet
    Morphine 15 mg/ml vial0.3USDml
    Morphine-ns 25 mg/25 ml syr0.26USDml
    M.O.S. Sulfate 25 mg Tablet0.25USDtablet
    Statex 25 mg Tablet0.25USDtablet
    Ms.Ir 10 mg Tablet0.21USDtablet
    Ratio-Morphine 10 mg/ml Syrup0.19USDsyrup
    M.O.S. Sulfate 10 mg Tablet0.19USDtablet
    Statex 10 mg Tablet0.19USDtablet
    Morphine-ns 5 mg/ml0.16USDml
    Morphine-ns 55 mg/55 ml syr0.14USDml
    Ms.Ir 5 mg Tablet0.14USDtablet
    M.O.S. Sulfate 5 mg Tablet0.12USDtablet
    Statex 5 mg Tablet0.12USDtablet
    Morphine 1 mg/ml-d5w 100 ml0.1USDml
    Morphine-ns 150 mg/150 ml0.1USDml
    Statex 5 mg/ml Syrup0.08USDml
    Morphine 1 mg/ml-d5w 250 ml0.06USDml
    Ratio-Morphine 5 mg/ml Syrup0.05USDsyrup
    Ratio-Morphine 1 mg/ml Syrup0.02USDsyrup
    Statex 1 mg/ml Syrup0.02USDml
    DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
    Patents
    CountryPatent NumberApprovedExpires (estimated)
    United States60663391997-11-252017-11-25
    United States53784741993-03-232010-03-23
    Canada20652102000-08-292012-04-06
    Canada21285911999-03-232014-07-21
    Properties
    Statesolid
    Experimental Properties
    PropertyValueSource
    melting point255 °CPhysProp
    water solubility149 mg/L (at 20 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
    logP0.89AVDEEF,A ET AL. (1996)
    logS-3.28ADME Research, USCD
    pKa8.21 (at 25 °C)LIDE,DR (1995)
    Predicted Properties
    PropertyValueSource
    water solubility1.02e+01 g/lALOGPS
    logP0.99ALOGPS
    logP0.9ChemAxon
    logS-1.4ALOGPS
    pKa (strongest acidic)10.26ChemAxon
    pKa (strongest basic)9.12ChemAxon
    physiological charge1ChemAxon
    hydrogen acceptor count4ChemAxon
    hydrogen donor count2ChemAxon
    polar surface area52.93ChemAxon
    rotatable bond count0ChemAxon
    refractivity80.12ChemAxon
    polarizability29.95ChemAxon
    number of rings5ChemAxon
    bioavailability1ChemAxon
    rule of fiveYesChemAxon
    Ghose filterYesChemAxon
    Veber's ruleNoChemAxon
    MDDR-like ruleNoChemAxon
    Spectra
    SpectraNot Available
    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.

    US4764615
    General Reference
    1. Kilpatrick GJ, Smith TW: Morphine-6-glucuronide: actions and mechanisms. Med Res Rev. 2005 Sep;25(5):521-44. Pubmed
    2. Loguinov AV, Anderson LM, Crosby GJ, Yukhananov RY: Gene expression following acute morphine administration. Physiol Genomics. 2001 Aug 28;6(3):169-81. Pubmed
    External Links
    ResourceLink
    KEGG DrugD00842
    KEGG CompoundC01516
    PubChem Compound5288826
    PubChem Substance46505161
    ChemSpider4450907
    ChEBI17303
    ChEMBLCHEMBL70
    Therapeutic Targets DatabaseDAP000071
    PharmGKBPA450550
    HETMOI
    Drug Product Database2245286
    RxListhttp://www.rxlist.com/cgi/generic/ms.htm
    Drugs.comhttp://www.drugs.com/morphine.html
    PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/msc1277.shtml
    WikipediaMorphine
    ATC CodesG04BE07N02AA01N02AA04N04BC07R05DA01R05DA05S01XA06D10AX30
    AHFS Codes
    • 84:24.12
    • 28:08.08
    PDB EntriesNot Available
    FDA labelshow(1.2 MB)
    MSDSshow(51.7 KB)
    Interactions
    Drug Interactions
    Drug
    AlvimopanIncreases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
    EltrombopagEltrombopag increases Morphine levels via decreasing metabolism. UDP-glucuronosyltransferase inhibition with unclear significance.
    RifampicinRifampin decreases the effect of morphine/codeine
    TriprolidineThe CNS depressants, Triprolidine and Morphine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
    TrovafloxacinMorphine may reduce serum levels of Trovafloxacin decreasing the efficacy of the antibiotic. IV doses of morphine should be administered at least 2 hours after a dose of Trovafloxacin given in a fasting state or 4 hours after if given in a fed state.
    Food Interactions
    • Avoid alcohol.
    • Take with food.
    • To avoid constipation: increase your daily intake of fiber (beans, whole grains, vegetables).

    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. Yamada H, Shimoyama N, Sora I, Uhl GR, Fukuda Y, Moriya H, Shimoyama M: Morphine can produce analgesia via spinal kappa opioid receptors in the absence of mu opioid receptors. Brain Res. 2006 Apr 14;1083(1):61-9. Epub 2006 Mar 10. Pubmed
    2. Kasai S, Han W, Ide S, Hata H, Takamatsu Y, Yamamoto H, Uhl GR, Sora I, Ikeda K: Involvement of the 3’ non-coding region of the mu opioid receptor gene in morphine-induced analgesia. Psychiatry Clin Neurosci. 2006 Apr;60 Suppl 1:S11-7. doi:10.1111/j.1440-1819.2006.01523.x-i1
    3. Choi HS, Kim CS, Hwang CK, Song KY, Wang W, Qiu Y, Law PY, Wei LN, Loh HH: The opioid ligand binding of human mu-opioid receptor is modulated by novel splice variants of the receptor. Biochem Biophys Res Commun. 2006 May 19;343(4):1132-40. Epub 2006 Mar 23. Pubmed
    4. Castro RR, Cunha FQ, Silva FS Jr, Rocha FA: A quantitative approach to measure joint pain in experimental osteoarthritis—evidence of a role for nitric oxide. Osteoarthritis Cartilage. 2006 Aug;14(8):769-76. Epub 2006 Mar 31. Pubmed
    5. Johnson EA, Oldfield S, Braksator E, Gonzalez-Cuello A, Couch D, Hall KJ, Mundell SJ, Bailey CP, Kelly E, Henderson G: Agonist-selective mechanisms of mu-opioid receptor desensitization in human embryonic kidney 293 cells. Mol Pharmacol. 2006 Aug;70(2):676-85. Epub 2006 May 8. Pubmed
    6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
    7. Yekkirala AS, Kalyuzhny AE, Portoghese PS: Standard opioid agonists activate heteromeric opioid receptors: evidence for morphine and [d-Ala2-MePhe4-Glyol5] enkephalin as selective μ−δ agonists. ACS Chem. Neurosci. 2010; 1(2):146-154 doi:10.1021/cn9000236

    2. Kappa-type opioid receptor

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: agonist

    Components

    Name UniProt ID Details
    Kappa-type opioid receptor P41145 Details

    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. Pubmed
    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. Pubmed
    3. Leventhal L, Silva RM, Rossi GC, Pasternak GW, Bodnar RJ: Morphine-6beta-glucuronide-induced hyperphagia: characterization of opioid action by selective antagonists and antisense mapping in rats. J Pharmacol Exp Ther. 1998 Nov;287(2):538-44. Pubmed
    4. Kozak CA, Filie J, Adamson MC, Chen Y, Yu L: Murine chromosomal location of the mu and kappa opioid receptor genes. Genomics. 1994 Jun;21(3):659-61. Pubmed
    5. Teodorov E, Modena CC, Sukikara MH, Felicio LF: Preliminary study of the effects of morphine treatment on opioid receptor gene expression in brain structures of the female rat. Neuroscience. 2006 Sep 1;141(3):1225-31. Epub 2006 Jun 6. Pubmed
    6. Yekkirala AS, Kalyuzhny AE, Portoghese PS: Standard opioid agonists activate heteromeric opioid receptors: evidence for morphine and [d-Ala2-MePhe4-Glyol5] enkephalin as selective μ−δ agonists. ACS Chem. Neurosci. 2010; 1(2):146-154 doi:10.1021/cn9000236

    3. 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. Yamada H, Shimoyama N, Sora I, Uhl GR, Fukuda Y, Moriya H, Shimoyama M: Morphine can produce analgesia via spinal kappa opioid receptors in the absence of mu opioid receptors. Brain Res. 2006 Apr 14;1083(1):61-9. Epub 2006 Mar 10. Pubmed
    2. Dortch-Carnes J, Russell KR: Morphine-induced reduction of intraocular pressure and pupil diameter: role of nitric oxide. Pharmacology. 2006;77(1):17-24. Epub 2006 Mar 13. Pubmed
    3. Koch T, Wu DF, Yang LQ, Brandenburg LO, Hollt V: Role of phospholipase D2 in the agonist-induced and constitutive endocytosis of G-protein coupled receptors. J Neurochem. 2006 Apr;97(2):365-72. Epub 2006 Mar 15. Pubmed
    4. Galeotti N, Stefano GB, Guarna M, Bianchi E, Ghelardini C: Signaling pathway of morphine induced acute thermal hyperalgesia in mice. Pain. 2006 Aug;123(3):294-305. Epub 2006 May 2. Pubmed
    5. Asensio VJ, Miralles A, Garcia-Sevilla JA: Stimulation of mitogen-activated protein kinase kinases (MEK1/2) by mu-, delta- and kappa-opioid receptor agonists in the rat brain: regulation by chronic morphine and opioid withdrawal. Eur J Pharmacol. 2006 Jun 6;539(1-2):49-56. Epub 2006 Apr 6. Pubmed
    6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
    7. Kieffer BL, Gaveriaux-Ruff C: Exploring the opioid system by gene knockout. Prog Neurobiol. 2002 Apr;66(5):285-306. Pubmed
    8. Yekkirala AS, Kalyuzhny AE, Portoghese PS: Standard opioid agonists activate heteromeric opioid receptors: evidence for morphine and [d-Ala2-MePhe4-Glyol5] enkephalin as selective μ−δ agonists. ACS Chem. Neurosci. 2010; 1(2):146-154 doi:10.1021/cn9000236

    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. 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 2C8

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    Cytochrome P450 2C8 P10632 Details

    References:

    1. 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

    3. Cytochrome P450 3A4

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    Cytochrome P450 3A4 P08684 Details

    References:

    1. 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

    4. UDP-glucuronosyltransferase 2B7

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    UDP-glucuronosyltransferase 2B7 P16662 Details

    References:

    1. Coffman BL, Rios GR, King CD, Tephly TR: Human UGT2B7 catalyzes morphine glucuronidation. Drug Metab Dispos. 1997 Jan;25(1):1-4. Pubmed
    2. Takeda S, Ishii Y, Iwanaga M, Mackenzie PI, Nagata K, Yamazoe Y, Oguri K, Yamada H: Modulation of UDP-glucuronosyltransferase function by cytochrome P450: evidence for the alteration of UGT2B7-catalyzed glucuronidation of morphine by CYP3A4. Mol Pharmacol. 2005 Mar;67(3):665-72. Epub 2004 Dec 20. Pubmed
    3. Yamada H, Ishii K, Ishii Y, Ieiri I, Nishio S, Morioka T, Oguri K: Formation of highly analgesic morphine-6-glucuronide following physiologic concentration of morphine in human brain. J Toxicol Sci. 2003 Dec;28(5):395-401. Pubmed
    4. Abildskov K, Weldy P, Garland M: Molecular cloning of the baboon UDP-glucuronosyltransferase 2B gene family and their activity in conjugating morphine. Drug Metab Dispos. 2010 Apr;38(4):545-53. Epub 2010 Jan 13. Pubmed

    5. UDP-glucuronosyltransferase 1-1

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    UDP-glucuronosyltransferase 1-1 P22309 Details

    References:

    1. Ohno S, Kawana K, Nakajin S: Contribution of UDP-glucuronosyltransferase 1A1 and 1A8 to morphine-6-glucuronidation and its kinetic properties. Drug Metab Dispos. 2008 Apr;36(4):688-94. Epub 2008 Jan 10. Pubmed

    6. UDP-glucuronosyltransferase 1-8

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    UDP-glucuronosyltransferase 1-8 Q9HAW9 Details

    References:

    1. Ohno S, Kawana K, Nakajin S: Contribution of UDP-glucuronosyltransferase 1A1 and 1A8 to morphine-6-glucuronidation and its kinetic properties. Drug Metab Dispos. 2008 Apr;36(4):688-94. Epub 2008 Jan 10. Pubmed

    7. UDP-glucuronosyltransferase 2B15

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    UDP-glucuronosyltransferase 2B15 P54855 Details

    References:

    1. Abildskov K, Weldy P, Garland M: Molecular cloning of the baboon UDP-glucuronosyltransferase 2B gene family and their activity in conjugating morphine. Drug Metab Dispos. 2010 Apr;38(4):545-53. Epub 2010 Jan 13. Pubmed

    8. UDP-glucuronosyltransferase 2B4

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    UDP-glucuronosyltransferase 2B4 P06133 Details

    References:

    1. Abildskov K, Weldy P, Garland M: Molecular cloning of the baboon UDP-glucuronosyltransferase 2B gene family and their activity in conjugating morphine. Drug Metab Dispos. 2010 Apr;38(4):545-53. Epub 2010 Jan 13. Pubmed

    9. UDP-glucuronosyltransferase 1-3

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    UDP-glucuronosyltransferase 1-3 P35503 Details

    References:

    1. Green MD, King CD, Mojarrabi B, Mackenzie PI, Tephly TR: Glucuronidation of amines and other xenobiotics catalyzed by expressed human UDP-glucuronosyltransferase 1A3. Drug Metab Dispos. 1998 Jun;26(6):507-12. Pubmed

    1. Multidrug resistance protein 1

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate inhibitor

    Components

    Name UniProt ID Details
    Multidrug resistance protein 1 P08183 Details

    References:

    1. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. Pubmed
    2. Troutman MD, Thakker DR: Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res. 2003 Aug;20(8):1210-24. Pubmed

    Comments
    Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:09