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Showing drug card for Naltrexone (DB00704)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-04-16 16:47:55
Primary Accession Number DB00704
Secondary Accession Number
  • APRD00005
Name Naltrexone
Drug Type
  • Approved
  • Investigational
  • Small Molecule
Description Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. [PubChem]
Synonyms
  1. PTI-555
  2. naltrexone
Brand Names
  1. Celupan
  2. MorViva
  3. N-Cyclopropylmethylnoroxymorphone
  4. Naltrexona [INN-Spanish]
  5. Naltrexone Hcl
  6. Naltrexone [Usan:Ban:Inn]
  7. Naltrexonum [INN-Latin]
  8. ReVia
  9. Vivitrex
Brand Mixtures Not Available
Chemical IUPAC Name Not Available
Chemical Formula C20H23NO4
Chemical Structure Structure
CAS Registry Number 16590-41-3
InChI Identifier InChI=1/C20H23NO4/c22-13-4-3-12-9-15-20(24)6-5-14(23)18-19(20,16(12)17(13)25-18)7-8-21(15)10-11-1-2-11/h3-4,11,15,18,22,24H,1-2,5-10H2/t15-,18+,19+,20-/m1/s1
InChI Key DQCKKXVULJGBQN-XFWGSAIBBM
KEGG Drug D05113 Link Image
KEGG Compound C07253 Link Image
PubChem Compound 5360515 Link Image
PubChem Substance 9462 Link Image
ChEBI ID Not Available
PharmGKB ID PA450588 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02213826 Link Image
RxList Link http://www.rxlist.com/cgi/generic2/naltrexone.htm Link Image
PDRhealth Link http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/rev1376.shtml Link Image
Wikipedia Link http://en.wikipedia.org/wiki/Naltrexone Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 341.4009
Monoisotopic Molecular Weight 341.1627
State Solid
Melting Point 169-170 oC (274-276 oC for hydrochloride salt)
Experimental Water Solubility 100 mg/mL (as hydrochloride salt) Source: PhysProp
Predicted Water Solubility 3.07e+00 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 0.7 Source: PhysProp
Predicted LogP 2.07 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -2.05 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES OC1=C2O[C@H]3C(=O)CC[C@@]4(O)[C@H]5CC(C=C1)=C2[C@@]34CCN5CC1CC1
Canonical SMILES OC1=C2OC3C(=O)CCC4(O)C5CC(C=C1)=C2C34CCN5CC1CC1
Drug Category
  • Alcohol Antagonists
  • Anti-craving Agents
  • Depressants
  • Narcotic Antagonists
  • Opiate Antagonists
ATC Codes
AHFS Codes
  • 28:10.00
Indication For use in the treatment of alcohol dependence and for the blockade of the effects of exogenously administered opioids.
Pharmacology Naltrexone, a pure opioid antagonist, is a synthetic congener of oxymorphone with no opioid agonist properties. Naltrexone is indicated in the treatment of alcohol dependence and for the blockade of the effects of exogenously administered opioids. It markedly attenuates or completely blocks, reversibly, the subjective effects of intravenously administered opioids. When co-administered with morphine, on a chronic basis, naltrexone blocks the physical dependence to morphine, heroin and other opioids. In subjects physically dependent on opioids, naltrexone will precipitate withdrawal symptomatology.
Mechanism of Action Naltrexone binds to the opioid mu receptor antagonistically, thereby preventing conventional opiate (heroin, morphine) drugs from binding and inducing opioid neural responses. The mechanism of action of naltrexone in alcoholism is not understood; however, involvement of the endogenous opioid system is suggested by preclinical data. Naltrexone competitively binds to such receptors and may block the effects of endogenous opioids.
Absorption Although well absorbed orally, naltrexone is subject to significant first pass metabolism with oral bioavailability estimates ranging from 5 to 40%.
Toxicity In the mouse, rat and guinea pig, the oral LD50s were 1,100-1,550 mg/kg; 1,450 mg/kg; and 1,490 mg/kg; respectively. High doses of naltrexone (generally ≥1,000 mg/kg) produce salivation, depression/reduced activity, tremors, and convulsions.
Protein Binding 21% bound to plasma proteins over the therapeutic dose range.
Biotransformation Hepatic. When administered orally, naltrexone undergoes extensive biotransformation and is metabolized to 6 beta-naltrexol (which may contribute to the therapeutic effect) and other minor metabolites.
Half Life 4 hours for naltrexone and 13 hours for the active metabolite 6 beta-naltrexol.
Dosage Forms
Form Route
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Alfentanil Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals
Buprenorphine Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals
Codeine Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals
Dihydrocodeine Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals
Fentanyl Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals
Heroin Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals
Hydrocodone Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals
Hydromorphone Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals
Levorphanol Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals
Meperidine Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals
Methadone Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals
Morphine Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals
Nalbuphine Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals
Oxycodone Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals
Oxymorphone Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals
Pentazocine Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals
Propoxyphene Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals
Sufentanil Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals
Food Interactions
  • Take without regard to meals.
Pathways Not Available
General References
  1. Schmitz JM, Stotts AL, Rhoades HM, Grabowski J: Naltrexone and relapse prevention treatment for cocaine-dependent patients. Addict Behav. 2001 Mar-Apr;26(2):167-80. [PubMed Link Image]
  2. Drugs.com Link Image
  3. Wikipedia Link Image
  4. RxList Link Image
  5. PDRhealth Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. Delta-type opioid receptor
  2. Kappa-type opioid receptor
  3. Tumor necrosis factor
  4. Mu-type opioid receptor
Drug Target 1 [top]
Target 1 ID 467
Target 1 Name Delta-type opioid receptor
Target 1 Synonyms
  1. DOR-1
Target 1 Gene Name OPRD1
Target 1 Protein Sequence >Delta-type opioid receptor 
MEPAPSAGAELQPPLFANASDAYPSAFPSAGANASGPPGARSASSLALAIAITALYSAVC
AVGLLGNVLVMFGIVRYTKMKTATNIYIFNLALADALATSTLPFQSAKYLMETWPFGELL
CKAVLSIDYYNMFTSIFTLTMMSVDRYIAVCHPVKALDFRTPAKAKLINICIWVLASGVG
VPIMVMAVTRPRDGAVVCMLQFPSPSWYWDTVTKICVFLFAFVVPILIITVCYGLMLLRL
RSVRLLSGSKEKDRSLRRITRMVLVVVGAFVVCWAPIHIFVIVWTLVDIDRRDPLVVAAL
HLCIALGYANSSLNPVLYAFLDENFKRCFRQLCRKPCGRPDPSSFSRAREATARERVTAC
TPSDGPGGGAAA
Target 1 Number of Residues 378
Target 1 Molecular Weight 40413
Target 1 Theoretical pI 9.17
Target 1 GO Classification
Function
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
peptide receptor activity, G-protein coupled
opioid receptor activity
delta-opioid receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 1 General Function Involved in delta-opioid receptor activity
Target 1 Specific Function Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Highly stereoselective. receptor for enkephalins
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 46-75
  • 85-102
  • 125-144
  • 175-190
  • 216-238
  • 262-284
  • 294-310
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 27545517 Link Image
Target 1 UniProtKB/Swiss-Prot ID P41143 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name OPRD_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >1119 bp 
ATGGAACCGGCCCCCTCCGCCGGCGCCGAGCTGCAGCCCCCGCTCTTCGCCAACGCCTCG
GACGCCTACCCTAGCGCCTTCCCCAGCGCTGGCGCCAATGCGTCGGGGCCGCCAGGCGCG
CGGAGCGCCTCGTCCCTCGCCCTGGCAATCGCCATCACCGCGCTCTACTCGGCCGTGTGC
GCCGTGGGGCTGCTGGGCAACGTGCTTGTCATGTTCGGCATCGTCCGGTACACTAAGATG
AAGACGGCCACCAACATCTACATCTTCAACCTGGCCTTAGCCGATGCGCTGGCCACCAGC
ACGCTGCCTTTCCAGAGTGCCAAGTACCTGATGGAGACGTGGCCCTTCGGCGAGCTGCTC
TGCAAGGCTGTGCTCTCCATCGACTACTACAATATGTTCACCAGCATCTTCACGCTCACC
ATGATGAGTGTTGACCGCTACATCGCTGTCTGCCACCCTGTCAAGGCCCTGGACTTCCGC
ACGCCTGCCAAGGCCAAGCTGATCAACATCTGTATCTGGGTCCTGGCCTCAGGCGTTGGC
GTGCCCATCATGGTCATGGCTGTGACCCGTCCCCGGGACGGGGCAGTGGTGTGCATGCTC
CAGTTCCCCAGCCCCAGCTGGTACTGGGACACGGTGACCAAGATCTGCGTGTTCCTCTTC
GCCTTCGTGGTGCCCATCCTCATCATCACCGTGTGCTATGGCCTCATGCTGCTGCGCCTG
CGCAGTGTGCGCCTGCTGTCGGGCTCCAAGGAGAAGGACCGCAGCCTGCGGCGCATCACG
CGCATGGTGCTGGTGGTTGTGGGCGCCTTCGTGGTGTGTTGGGCGCCCATCCACATCTTC
GTCATCGTCTGGACGCTGGTGGACATCGACCGGCGCGACCCGCTGGTGGTGGCTGCGCTG
CACCTGTGCATCGCGCTGGGCTACGCCAATAGCAGCCTCAACCCCGTGCTCTACGCTTTC
CTCGACGAGAACTTCAAGCGCTGCTTCCGCCAGCTCTGCCGCAAGCCCTGCGGCCGCCCA
GACCCCAGCAGCTTCAGCCGCGCCCGCGAAGCCACGGCCCGCGAGCGTGTCACCGCCTGC
ACCCCGTCCGATGGTCCCGGCGGTGGCGCTGCCGCCTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID OPRD1 Link Image
Target 1 GenAtlas ID OPRD1 Link Image
Target 1 HGNC ID HGNC:8153 Link Image
Target 1 Chromosome Location 1
Target 1 Locus 1p36.1-p34.3
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Gelernter J, Kranzler HR: Variant detection at the delta opioid receptor (OPRD1) locus and population genetics of a novel variant affecting protein sequence. Hum Genet. 2000 Jul;107(1):86-8. [PubMed Link Image]
  2. Simonin F, Befort K, Gaveriaux-Ruff C, Matthes H, Nappey V, Lannes B, Micheletti G, Kieffer B: The human delta-opioid receptor: genomic organization, cDNA cloning, functional expression, and distribution in human brain. Mol Pharmacol. 1994 Dec;46(6):1015-21. [PubMed Link Image]
  3. Knapp RJ, Malatynska E, Fang L, Li X, Babin E, Nguyen M, Santoro G, Varga EV, Hruby VJ, Roeske WR, et al.: Identification of a human delta opioid receptor: cloning and expression. Life Sci. 1994;54(25):PL463-9. [PubMed Link Image]
Target 1 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 696
Target 2 Name Kappa-type opioid receptor
Target 2 Synonyms
  1. KOR-1
Target 2 Gene Name OPRK1
Target 2 Protein Sequence >Kappa-type opioid receptor 
MDSPIQIFRGEPGPTCAPSACLPPNSSAWFPGWAEPDSNGSAGSEDAQLEPAHISPAIPV
IITAVYSVVFVVGLVGNSLVMFVIIRYTKMKTATNIYIFNLALADALVTTTMPFQSTVYL
MNSWPFGDVLCKIVISIDYYNMFTSIFTLTMMSVDRYIAVCHPVKALDFRTPLKAKIINI
CIWLLSSSVGISAIVLGGTKVREDVDVIECSLQFPDDDYSWWDLFMKICVFIFAFVIPVL
IIIVCYTLMILRLKSVRLLSGSREKDRNLRRITRLVLVVVAVFVVCWTPIHIFILVEALG
STSHSTAALSSYYFCIALGYTNSSLNPILYAFLDENFKRCFRDFCFPLKMRMERQSTSRV
RNTVQDPAYLRDIDGMNKPV
Target 2 Number of Residues 386
Target 2 Molecular Weight 42646
Target 2 Theoretical pI 7.79
Target 2 GO Classification
Function
peptide receptor activity, G-protein coupled
opioid receptor activity
kappa-opioid receptor activity
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 2 General Function Involved in rhodopsin-like receptor activity
Target 2 Specific Function Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for dynorphins. May play a role in arousal and regulation of autonomic and neuroendocrine functions
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • 59-85
  • 96-117
  • 133-154
  • 174-196
  • 223-247
  • 276-299
  • 312-333
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 532060 Link Image
Target 2 UniProtKB/Swiss-Prot ID P41145 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name OPRK_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 2 Gene Sequence >1143 bp 
ATGGAATCCCCGATTCAGATCTTCCGCGGGGAGCCTGGCCCTACCTGCGCCCCGAGCGCC
TGCCTGCCCCCCAACAGCAGCGCCTGGTTTCCCGGCTGGGCCGAGCCCGACAGCAACGGC
AGCGCCGGCTCGGAGGACGCGCAGCTGGAGCCCGCGCACATCTCCCCGGCCATCCCGGTC
ATCATCACGGCGGTCTACTCCGTAGTGTTCGTCGTGGGCTTGGTGGGCAACTCGCTGGTC
ATGTTCGTGATCATCCGATACACAAAGATGAAGACAGCAACCAACATTTACATATTTAAC
CTGGCTTTGGCAGATGCTTTAGTTACTACAACCATGCCCTTTCAGAGTACGGTCTACTTG
ATGAATTCCTGGCCTTTTGGGGATGTGCTGTGCAAGATAGTAATTTCCATTGATTACTAC
AACATGTTCACCAGCATCTTCACCTTGACCATGATGAGCGTGGACCGCTACATTGCCGTG
TGCCACCCCGTGAAGGCTTTGGACTTCCGCACACCCTTGAAGGCAAAGATCATCAATATC
TGCATCTGGCTGCTGTCGTCATCTGTTGGCATCTCTGCAATAGTCCTTGGAGGCACCAAA
GTCAGGGAAGACGTCGATGTCATTGAGTGCTCCTTGCAGTTCCCAGATGATGACTACTCC
TGGTGGGACCTCTTCATGAAGATCTGCGTCTTCATCTTTGCCTTCGTGATCCCTGTCCTC
ATCATCATCGTCTGCTACACCCTGATGATCCTGCGTCTCAAGAGCGTCCGGCTCCTTTCT
GGCTCCCGAGAGAAAGATCGCAACCTGCGTAGGATCACCAGACTGGTCCTGGTGGTGGTG
GCGGTTTTCGTCGTCTGCTGGACTCCCATTCACATATTCATCCTGGTGGAGGCTCTGGGG
AGCACCTCCCACAGCACAGCTGCTCTCTCCAGCTATTACTTCTGCATCGCCTTAGGCTAT
ACCAACAGTAGCCTGAATCCCATTCTCTACGCCTTTCTTGATGAAAACTTCAAGCGGTGT
TTCCGGGACTTCTGCTTTCCACTGAAGATGAGGATGGAGCGGCAGAGCACTAGCAGAGTC
CGAAATACAGTTCAGGATCCTGCTTACCTGAGGGACATCGATGGGATGAATAAACCAGTA
TGA
Target 2 GenBank Gene ID
Target 2 GeneCard ID OPRK1 Link Image
Target 2 GenAtlas ID OPRK1 Link Image
Target 2 HGNC ID HGNC:8154 Link Image
Target 2 Chromosome Location 8
Target 2 Locus 8q11.2
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Li JG, Chen C, Liu-Chen LY: Ezrin-radixin-moesin-binding phosphoprotein-50/Na+/H+ exchanger regulatory factor (EBP50/NHERF) blocks U50,488H-induced down-regulation of the human kappa opioid receptor by enhancing its recycling rate. J Biol Chem. 2002 Jul 26;277(30):27545-52. Epub 2002 May 9. [PubMed Link Image]
  2. Simonin F, Gaveriaux-Ruff C, Befort K, Matthes H, Lannes B, Micheletti G, Mattei MG, Charron G, Bloch B, Kieffer B: kappa-Opioid receptor in humans: cDNA and genomic cloning, chromosomal assignment, functional expression, pharmacology, and expression pattern in the central nervous system. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):7006-10. [PubMed Link Image]
  3. Zhu J, Chen C, Xue JC, Kunapuli S, DeRiel JK, Liu-Chen LY: Cloning of a human kappa opioid receptor from the brain. Life Sci. 1995;56(9):PL201-7. [PubMed Link Image]
  4. Wang JB, Johnson PS, Wu JM, Wang WF, Uhl GR: Human kappa opiate receptor second extracellular loop elevates dynorphin's affinity for human mu/kappa chimeras. J Biol Chem. 1994 Oct 21;269(42):25966-9. [PubMed Link Image]
  5. Mansson E, Bare L, Yang D: Isolation of a human kappa opioid receptor cDNA from placenta. Biochem Biophys Res Commun. 1994 Aug 15;202(3):1431-7. [PubMed Link Image]
Target 2 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 777
Target 3 Name Tumor necrosis factor
Target 3 Synonyms
  1. Cachectin
  2. TNF-a
  3. TNF-alpha
  4. Tumor necrosis factor ligand superfamily member 2
  5. Tumor necrosis factor precursor
Target 3 Gene Name TNF
Target 3 Protein Sequence >Tumor necrosis factor precursor 
MSTESMIRDVELAEEALPKKTGGPQGSRRCLFLSLFSFLIVAGATTLFCLLHFGVIGPQR
EEFPRDLSLISPLAQAVRSSSRTPSDKPVAHVVANPQAEGQLQWLNRRANALLANGVELR
DNQLVVPSEGLYLIYSQVLFKGQGCPSTHVLLTHTISRIAVSYQTKVNLLSAIKSPCQRE
TPEGAEAKPWYEPIYLGGVFQLEKGDRLSAEINRPDYLDFAESGQVYFGIIAL
Target 3 Number of Residues 236
Target 3 Molecular Weight 25645
Target 3 Theoretical pI 6.92
Target 3 GO Classification
Function
signal transducer activity
receptor binding
cytokine activity
tumor necrosis factor receptor binding
Process
response to stimulus
response to biotic stimulus
defense response
immune response
Component
cell
membrane
Target 3 General Function Involved in tumor necrosis factor receptor binding
Target 3 Specific Function Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin 1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • 36-56
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 339741 Link Image
Target 3 UniProtKB/Swiss-Prot ID P01375 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name TNFA_HUMAN Link Image
Target 3 PDB ID 1A8M Link Image
Target 3 PDB File Show
Target 3 3D Structure
Target 3 Cellular Location
  • Cell membrane
  • single-pass type II membrane protein. Processed form:Secreted protein. Also exists as
Target 3 Gene Sequence >702 bp 
ATGAGCACTGAAAGCATGATCCGGGACGTGGAGCTGGCCGAGGAGGCGCTCCCCAAGAAG
ACAGGGGGGCCCCAGGGCTCCAGGCGGTGCTTGTTCCTCAGCCTCTTCTCCTTCCTGATC
GTGGCAGGCGCCACCACGCTCTTCTGCCTGCTGCACTTTGGAGTGATCGGCCCCCAGAGG
GAAGAGTTCCCCAGGGACCTCTCTCTAATCAGCCCTCTGGCCCAGGCAGTCAGATCATCT
TCTCGAACCCCGAGTGACAAGCCTGTAGCCCATGTTGTAGCAAACCCTCAAGCTGAGGGG
CAGCTCCAGTGGCTGAACCGCCGGGCCAATGCCCTCCTGGCCAATGGCGTGGAGCTGAGA
GATAACCAGCTGGTGGTGCCATCAGAGGGCCTGTACCTCATCTACTCCCAGGTCCTCTTC
AAGGGCCAAGGCTGCCCCTCCACCCATGTGCTCCTCACCCACACCATCAGCCGCATCGCC
GTCTCCTACCAGACCAAGGTCAACCTCCTCTCTGCCATCAAGAGCCCCTGCCAGAGGGAG
ACCCCAGAGGGGGCTGAGGCCAAGCCCTGGTATGAGCCCATCTATCTGGGAGGGGTCTTC
CAGCTGGAGAAGGGTGACCGACTCAGCGCTGAGATCAATCGGCCCGACTATCTCGACTTT
GCCGAGTCTGGGCAGGTCTACTTTGGGATCATTGCCCTGTGA
Target 3 GenBank Gene ID
Target 3 GeneCard ID TNF Link Image
Target 3 GenAtlas ID TNF Link Image
Target 3 HGNC ID HGNC:11892 Link Image
Target 3 Chromosome Location 6
Target 3 Locus 6p21.3
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Neville MJ, Campbell RD: A new member of the Ig superfamily and a V-ATPase G subunit are among the predicted products of novel genes close to the TNF locus in the human MHC. J Immunol. 1999 Apr 15;162(8):4745-54. [PubMed Link Image]
  2. Watts AD, Hunt NH, Wanigasekara Y, Bloomfield G, Wallach D, Roufogalis BD, Chaudhri G: A casein kinase I motif present in the cytoplasmic domain of members of the tumour necrosis factor ligand family is implicated in 'reverse signalling'. EMBO J. 1999 Apr 15;18(8):2119-26. [PubMed Link Image]
  3. Stevenson FT, Bursten SL, Locksley RM, Lovett DH: Myristyl acylation of the tumor necrosis factor alpha precursor on specific lysine residues. J Exp Med. 1992 Oct 1;176(4):1053-62. [PubMed Link Image]
  4. Jones EY, Stuart DI, Walker NP: The structure of tumour necrosis factor--implications for biological function. J Cell Sci Suppl. 1990;13:11-8. [PubMed Link Image]
  5. Van Ostade X, Tavernier J, Prange T, Fiers W: Localization of the active site of human tumour necrosis factor (hTNF) by mutational analysis. EMBO J. 1991 Apr;10(4):827-36. [PubMed Link Image]
  6. Eck MJ, Sprang SR: The structure of tumor necrosis factor-alpha at 2.6 A resolution. Implications for receptor binding. J Biol Chem. 1989 Oct 15;264(29):17595-605. [PubMed Link Image]
  7. Jones EY, Stuart DI, Walker NP: Structure of tumour necrosis factor. Nature. 1989 Mar 16;338(6212):225-8. [PubMed Link Image]
  8. Nedwin GE, Naylor SL, Sakaguchi AY, Smith D, Jarrett-Nedwin J, Pennica D, Goeddel DV, Gray PW: Human lymphotoxin and tumor necrosis factor genes: structure, homology and chromosomal localization. Nucleic Acids Res. 1985 Sep 11;13(17):6361-73. [PubMed Link Image]
  9. Nedospasov SA, Shakhov AN, Turetskaya RL, Mett VA, Azizov MM, Georgiev GP, Korobko VG, Dobrynin VN, Filippov SA, Bystrov NS, et al.: Tandem arrangement of genes coding for tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta) in the human genome. Cold Spring Harb Symp Quant Biol. 1986;51 Pt 1:611-24. [PubMed Link Image]
  10. Wang AM, Creasey AA, Ladner MB, Lin LS, Strickler J, Van Arsdell JN, Yamamoto R, Mark DF: Molecular cloning of the complementary DNA for human tumor necrosis factor. Science. 1985 Apr 12;228(4696):149-54. [PubMed Link Image]
  11. 3883195 Shirai T, Yamaguchi H, Ito H, Todd CW, Wallace RB: Cloning and expression in Escherichia coli of the gene for human tumour necrosis factor. Nature. 1985 Feb 28-Mar 6;313(6005):803-6.
  12. 3932069 Marmenout A, Fransen L, Tavernier J, Van der Heyden J, Tizard R, Kawashima E, Shaw A, Johnson MJ, Semon D, Muller R, et al.: Molecular cloning and expression of human tumor necrosis factor and comparison with mouse tumor necrosis factor. Eur J Biochem. 1985 Nov 4;152(3):515-22.
  13. 6392892 Pennica D, Nedwin GE, Hayflick JS, Seeburg PH, Derynck R, Palladino MA, Kohr WJ, Aggarwal BB, Goeddel DV: Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature. 1984 Dec 20-1985 Jan 2;312(5996):724-9.
  14. 8499947 Iris FJ, Bougueleret L, Prieur S, Caterina D, Primas G, Perrot V, Jurka J, Rodriguez-Tome P, Claverie JM, Dausset J, et al.: Dense Alu clustering and a potential new member of the NF kappa B family within a 90 kilobase HLA class III segment. Nat Genet. 1993 Feb;3(2):137-45.
  15. 8597870 Pocsik E, Duda E, Wallach D: Phosphorylation of the 26 kDa TNF precursor in monocytic cells and in transfected HeLa cells. J Inflamm. 1995;45(3):152-60.
  16. 9034191 Moss ML, Jin SL, Milla ME, Bickett DM, Burkhart W, Carter HL, Chen WJ, Clay WC, Didsbury JR, Hassler D, Hoffman CR, Kost TA, Lambert MH, Leesnitzer MA, McCauley P, McGeehan G, Mitchell J, Moyer M, Pahel G, Rocque W, Overton LK, Schoenen F, Seaton T, Su JL, Becherer JD, et al.: Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha. Nature. 1997 Feb 20;385(6618):733-6.
  17. 9442056 Cha SS, Kim JS, Cho HS, Shin NK, Jeong W, Shin HC, Kim YJ, Hahn JH, Oh BH: High resolution crystal structure of a human tumor necrosis factor-alpha mutant with low systemic toxicity. J Biol Chem. 1998 Jan 23;273(4):2153-60.
  18. 9488135 Reed C, Fu ZQ, Wu J, Xue YN, Harrison RW, Chen MJ, Weber IT: Crystal structure of TNF-alpha mutant R31D with greater affinity for receptor R1 compared with R2. Protein Eng. 1997 Oct;10(10):1101-7.
Target 3 Drug References
  1. Greeneltch KM, Haudenschild CC, Keegan AD, Shi Y: The opioid antagonist naltrexone blocks acute endotoxic shock by inhibiting tumor necrosis factor-alpha production. Brain Behav Immun. 2004 Sep;18(5):476-84. [PubMed Link Image]
  2. Lin SL, Lee YM, Chang HY, Cheng YW, Yen MH: Effects of naltrexone on lipopolysaccharide-induced sepsis in rats. J Biomed Sci. 2005;12(2):431-40. [PubMed Link Image]
  3. Davis RL, Buck DJ, Saffarian N, Stevens CW: The opioid antagonist, beta-funaltrexamine, inhibits chemokine expression in human astroglial cells. J Neuroimmunol. 2007 May;186(1-2):141-9. Epub 2007 May 1. [PubMed Link Image]
Drug Target 4 [top]
Target 4 ID 847
Target 4 Name Mu-type opioid receptor
Target 4 Synonyms
  1. MOR-1
Target 4 Gene Name OPRM1
Target 4 Protein Sequence >Mu-type opioid receptor 
MDSSAAPTNASNCTDALAYSSCSPAPSPGSWVNLSHLDGNLSDPCGPNRTDLGGRDSLCP
PTGSPSMITAITIMALYSIVCVVGLFGNFLVMYVIVRYTKMKTATNIYIFNLALADALAT
STLPFQSVNYLMGTWPFGTILCKIVISIDYYNMFTSIFTLCTMSVDRYIAVCHPVKALDF
RTPRNAKIINVCNWILSSAIGLPVMFMATTKYRQGSIDCTLTFSHPTWYWENLLKICVFI
FAFIMPVLIITVCYGLMILRLKSVRMLSGSKEKDRNLRRITRMVLVVVAVFIVCWTPIHI
YVIIKALVTIPETTFQTVSWHFCIALGYTNSCLNPVLYAFLDENFKRCFREFCIPTSSNI
EQQNSTRIRQNTRDHPSTANTVDRTNHQLENLEAETAPLP
Target 4 Number of Residues 406
Target 4 Molecular Weight 44780
Target 4 Theoretical pI 8.29
Target 4 GO Classification
Function
peptide receptor activity, G-protein coupled
opioid receptor activity
mu-opioid receptor activity
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 4 General Function Involved in rhodopsin-like receptor activity
Target 4 Specific Function Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for beta-endorphin
Target 4 Pathways Not Available
Target 4 Reactions Not Available
Target 4 Pfam Domain Function
Target 4 Signals
  • None
Target 4 Transmembrane Regions
  • 67-96
  • 106-123
  • 146-165
  • 196-211
  • 237-259
  • 283-305
  • 314-330
Target 4 Essentiality Non-Essential
Target 4 GenBank ID Protein 452073 Link Image
Target 4 UniProtKB/Swiss-Prot ID P35372 Link Image
Target 4 UniProtKB/Swiss-Prot Entry Name OPRM_HUMAN Link Image
Target 4 PDB ID Not Available
Target 4 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 4 Gene Sequence >1203 bp 
ATGGACAGCAGCGCTGCCCCCACGAACGCCAGCAATTGCACTGATGCCTTGGCGTACTCA
AGTTGCTCCCCAGCACCCAGCCCCGGTTCCTGGGTCAACTTGTCCCACTTAGATGGCAAC
CTGTCCGACCCATGCGGTCCGAACCGCACCAACCTGGGCGGGAGAGACAGCCTGTGCCCT
CCGACCGGCAGTCCCTCCATGATCACGGCCATCACGATCATGGCCCTCTACTCCATCGTG
TGCGTGGTGGGGCTCTTCGGAAACTTCCTGGTCATGTATGTGATTGTCAGATACACCAAG
ATGAAGACTGCCACCAACATCTACATTTTCAACCTTGCTCTGGCAGATGCCTTAGCCACC
AGTACCCTGCCCTTCCAGAGTGTGAATTACCTAATGGGAACATGGCCATTTGGAACCATC
CTTTGCAAGATAGTGATCTCCATAGATTACTATAACATGTTCACCAGCATATTCACCCTC
TGCACCATGAGTGTTGATCGATACATTGCAGTCTGCCACCCTGTCAAGGCCTTAGATTTC
CGTACTCCCCGAAATGCCAAAATTATCAATGTCTGCAACTGGATCCTCTCTTCAGCCATT
GGTCTTCCTGTAATGTTCATGGCTACAACAAAATACAGGCAAGGTTCCATAGATTGTACA
CTAACATTCTCTCATCCAACCTGGTACTGGGAAAACCTCGTGAAGATCTGTGTTTTCATC
TTCGCCTTCATTATGCCAGTGCTCATCATTACCGTGTGCTATGGACTGATGATCTTGCGC
CTCAAGAGTGTCCGCATGCTCTCTGGCTCCAAAGAAAAGGACAGGAATCTTCGAAGGATC
ACCAGGATGGTGCTGGTGGTGGTGGCTGTGTTCATCGTCTGCTGGACTCCCATTCACATT
TACGTCATCATTAAAGCCTTGGTTACAATCCCAGAAACTACGTTCCAGACTGTTTCTTGG
CACTTCTGCATTGCTCTAGGTTACACAAACAGCTGCCTCAACCCAGTCCTTTATGCATTT
CTGGATGAAAACTTCAAACGATGCTTCAGAGAGTTCTGTATCCCAACCTCTTCCAACATT
GAGCAACAAAACTCCACTCGAATTCGTCAGAACACTAGAGACCACCCCTCCACGGCCAAT
ACAGTGGATAGAACTAATCATCAGCTAGAAAATCTGGAAGCAGAAACTGCTCCGTTGCCC
TAA
Target 4 GenBank Gene ID
Target 4 GeneCard ID OPRM1 Link Image
Target 4 GenAtlas ID OPRM1 Link Image
Target 4 HGNC ID HGNC:8156 Link Image
Target 4 Chromosome Location 6
Target 4 Locus 6q24-q25
Target 4 SNPs SNPJam Report Link Image
Target 4 General References
  1. Uhl GR, Sora I, Wang Z: The mu opiate receptor as a candidate gene for pain: polymorphisms, variations in expression, nociception, and opiate responses. Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7752-5. [PubMed Link Image]
  2. Chuang TK, Killam KF Jr, Chuang LF, Kung HF, Sheng WS, Chao CC, Yu L, Chuang RY: Mu opioid receptor gene expression in immune cells. Biochem Biophys Res Commun. 1995 Nov 22;216(3):922-30. [PubMed Link Image]
  3. Mestek A, Hurley JH, Bye LS, Campbell AD, Chen Y, Tian M, Liu J, Schulman H, Yu L: The human mu opioid receptor: modulation of functional desensitization by calcium/calmodulin-dependent protein kinase and protein kinase C. J Neurosci. 1995 Mar;15(3 Pt 2):2396-406. [PubMed Link Image]
  4. Wang JB, Johnson PS, Persico AM, Hawkins AL, Griffin CA, Uhl GR: Human mu opiate receptor. cDNA and genomic clones, pharmacologic characterization and chromosomal assignment. FEBS Lett. 1994 Jan 31;338(2):217-22. [PubMed Link Image]
  5. Bare LA, Mansson E, Yang D: Expression of two variants of the human mu opioid receptor mRNA in SK-N-SH cells and human brain. FEBS Lett. 1994 Nov 7;354(2):213-6. [PubMed Link Image]
  6. Bergen AW, Kokoszka J, Peterson R, Long JC, Virkkunen M, Linnoila M, Goldman D: Mu opioid receptor gene variants: lack of association with alcohol dependence. Mol Psychiatry. 1997 Oct-Nov;2(6):490-4. [PubMed Link Image]
  7. Bond C, LaForge KS, Tian M, Melia D, Zhang S, Borg L, Gong J, Schluger J, Strong JA, Leal SM, Tischfield JA, Kreek MJ, Yu L: Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction. Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9608-13. [PubMed Link Image]
Target 4 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
  2. Oslin DW, Berrettini W, Kranzler HR, Pettinati H, Gelernter J, Volpicelli JR, O'Brien CP: A functional polymorphism of the mu-opioid receptor gene is associated with naltrexone response in alcohol-dependent patients. Neuropsychopharmacology. 2003 Aug;28(8):1546-52. Epub 2003 Jun 18. [PubMed Link Image]
  3. Bartus RT, Emerich DF, Hotz J, Blaustein M, Dean RL, Perdomo B, Basile AS: Vivitrex, an injectable, extended-release formulation of naltrexone, provides pharmacokinetic and pharmacodynamic evidence of efficacy for 1 month in rats. Neuropsychopharmacology. 2003 Nov;28(11):1973-82. [PubMed Link Image]
  4. Yoburn BC, Purohit V, Patel K, Zhang Q: Opioid agonist and antagonist treatment differentially regulates immunoreactive mu-opioid receptors and dynamin-2 in vivo. Eur J Pharmacol. 2004 Sep 13;498(1-3):87-96. [PubMed Link Image]
  5. Roy S, Guo X, Kelschenbach J, Liu Y, Loh HH: In vivo activation of a mutant mu-opioid receptor by naltrexone produces a potent analgesic effect but no tolerance: role of mu-receptor activation and delta-receptor blockade in morphine tolerance. J Neurosci. 2005 Mar 23;25(12):3229-33. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.