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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:50 UTC
Update Date2022-03-07 02:51:48 UTC
HMDB IDHMDB0014982
Secondary Accession Numbers
  • HMDB14982
Metabolite Identification
Common NameNalbuphine
DescriptionNalbuphine is only found in individuals that have used or taken this drug. It is a narcotic used as a pain medication. It appears to be an agonist at kappa opioid receptors and an antagonist or partial agonist at mu opioid receptors. [PubChem]The exact mechanism of action is unknown, but is believed to interact with an opiate receptor site in the CNS (probably in or associated with the limbic system). The opiate antagonistic effect may result from competitive inhibition at the opiate receptor, but may also be a result of other mechanisms. Nalbuphine is thought primarily to be a kappa agonist. It is also a partial mu antagonist analgesic, with some binding to the delta receptor and minimal agonist activity at the sigma receptor.
Structure
Data?1582753244
Synonyms
ValueSource
N-Cyclobutylmethyl-4,5alpha-epoxy-3,6alpha,14-morphinantriolChEBI
NalbufinaChEBI
NalbuphinumChEBI
IntapanKegg
N-Cyclobutylmethyl-4,5a-epoxy-3,6a,14-morphinantriolGenerator
N-Cyclobutylmethyl-4,5α-epoxy-3,6α,14-morphinantriolGenerator
NubainHMDB
Nalbuphine serb brandHMDB
Hydrochloride, nalbuphineHMDB
Serb, nalbuphineHMDB
Nalbuphine hydrochlorideHMDB
Nalbuphine serbHMDB
SERB brand OF nalbuphineHMDB
Chemical FormulaC21H27NO4
Average Molecular Weight357.4434
Monoisotopic Molecular Weight357.194008357
IUPAC Name(1S,5R,13R,14S,17S)-4-(cyclobutylmethyl)-12-oxa-4-azapentacyclo[9.6.1.0¹,¹³.0⁵,¹⁷.0⁷,¹⁸]octadeca-7,9,11(18)-triene-10,14,17-triol
Traditional Namenalbuphine
CAS Registry Number20594-83-6
SMILES
O[C@H]1CC[C@@]2(O)[C@H]3CC4=CC=C(O)C5=C4[C@@]2(CCN3CC2CCC2)[C@H]1O5
InChI Identifier
InChI=1S/C21H27NO4/c23-14-5-4-13-10-16-21(25)7-6-15(24)19-20(21,17(13)18(14)26-19)8-9-22(16)11-12-2-1-3-12/h4-5,12,15-16,19,23-25H,1-3,6-11H2/t15-,16+,19-,20-,21+/m0/s1
InChI KeyNETZHAKZCGBWSS-CEDHKZHLSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as phenanthrenes and derivatives. These are polycyclic compounds containing a phenanthrene moiety, which is a tricyclic aromatic compound with three non-linearly fused benzene.
KingdomOrganic compounds
Super ClassBenzenoids
ClassPhenanthrenes and derivatives
Sub ClassNot Available
Direct ParentPhenanthrenes and derivatives
Alternative Parents
Substituents
  • Phenanthrene
  • Tetralin
  • Coumaran
  • 1-hydroxy-2-unsubstituted benzenoid
  • Alkyl aryl ether
  • Aralkylamine
  • Piperidine
  • Cyclic alcohol
  • Tertiary alcohol
  • 1,2-aminoalcohol
  • Secondary alcohol
  • Tertiary aliphatic amine
  • Tertiary amine
  • Ether
  • Oxacycle
  • Polyol
  • Azacycle
  • Organoheterocyclic compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Alcohol
  • Organic oxygen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Biological location

Process

Naturally occurring process

Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting Point230 °C (hydrochloride salt)Not Available
Boiling PointNot AvailableNot Available
Water Solubility2.09 g/LNot Available
LogP1.4Not Available
Experimental Chromatographic Properties

Experimental Collision Cross Sections

Adduct TypeData SourceCCS Value (Å2)Reference
[M+H]+Not Available180.817http://allccs.zhulab.cn/database/detail?ID=AllCCS00000776
Predicted Molecular Properties
PropertyValueSource
Water Solubility2.09 g/LALOGPS
logP2ALOGPS
logP1.19ChemAxon
logS-2.2ALOGPS
pKa (Strongest Acidic)7.45ChemAxon
pKa (Strongest Basic)13.75ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area73.16 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity97 m³·mol⁻¹ChemAxon
Polarizability38.59 ųChemAxon
Number of Rings6ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DarkChem[M+H]+179.40231661259
DarkChem[M-H]-174.40331661259
DeepCCS[M+H]+183.20430932474
DeepCCS[M-H]-180.80830932474
DeepCCS[M-2H]-214.61330932474
DeepCCS[M+Na]+189.40230932474

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
NalbuphineO[C@H]1CC[C@@]2(O)[C@H]3CC4=CC=C(O)C5=C4[C@@]2(CCN3CC2CCC2)[C@H]1O54006.8Standard polar33892256
NalbuphineO[C@H]1CC[C@@]2(O)[C@H]3CC4=CC=C(O)C5=C4[C@@]2(CCN3CC2CCC2)[C@H]1O52976.4Standard non polar33892256
NalbuphineO[C@H]1CC[C@@]2(O)[C@H]3CC4=CC=C(O)C5=C4[C@@]2(CCN3CC2CCC2)[C@H]1O53087.1Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Nalbuphine,1TMS,isomer #1C[Si](C)(C)O[C@H]1CC[C@@]2(O)[C@H]3CC4=CC=C(O)C5=C4[C@@]2(CCN3CC2CCC2)[C@H]1O52889.1Semi standard non polar33892256
Nalbuphine,1TMS,isomer #2C[Si](C)(C)O[C@@]12CC[C@H](O)[C@@H]3OC4=C(O)C=CC5=C4[C@@]31CCN(CC1CCC1)[C@@H]2C52877.2Semi standard non polar33892256
Nalbuphine,1TMS,isomer #3C[Si](C)(C)OC1=CC=C2C[C@H]3N(CC4CCC4)CC[C@]45C2=C1O[C@H]4[C@@H](O)CC[C@@]35O2931.9Semi standard non polar33892256
Nalbuphine,2TMS,isomer #1C[Si](C)(C)O[C@H]1CC[C@@]2(O[Si](C)(C)C)[C@H]3CC4=CC=C(O)C5=C4[C@@]2(CCN3CC2CCC2)[C@H]1O52820.9Semi standard non polar33892256
Nalbuphine,2TMS,isomer #2C[Si](C)(C)OC1=CC=C2C[C@H]3N(CC4CCC4)CC[C@]45C2=C1O[C@H]4[C@@H](O[Si](C)(C)C)CC[C@@]35O2890.3Semi standard non polar33892256
Nalbuphine,2TMS,isomer #3C[Si](C)(C)OC1=CC=C2C[C@H]3N(CC4CCC4)CC[C@]45C2=C1O[C@H]4[C@@H](O)CC[C@@]35O[Si](C)(C)C2868.5Semi standard non polar33892256
Nalbuphine,3TMS,isomer #1C[Si](C)(C)OC1=CC=C2C[C@H]3N(CC4CCC4)CC[C@]45C2=C1O[C@H]4[C@@H](O[Si](C)(C)C)CC[C@@]35O[Si](C)(C)C2871.6Semi standard non polar33892256
Nalbuphine,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)O[C@H]1CC[C@@]2(O)[C@H]3CC4=CC=C(O)C5=C4[C@@]2(CCN3CC2CCC2)[C@H]1O53120.5Semi standard non polar33892256
Nalbuphine,1TBDMS,isomer #2CC(C)(C)[Si](C)(C)O[C@@]12CC[C@H](O)[C@@H]3OC4=C(O)C=CC5=C4[C@@]31CCN(CC1CCC1)[C@@H]2C53114.8Semi standard non polar33892256
Nalbuphine,1TBDMS,isomer #3CC(C)(C)[Si](C)(C)OC1=CC=C2C[C@H]3N(CC4CCC4)CC[C@]45C2=C1O[C@H]4[C@@H](O)CC[C@@]35O3166.5Semi standard non polar33892256
Nalbuphine,2TBDMS,isomer #1CC(C)(C)[Si](C)(C)O[C@H]1CC[C@@]2(O[Si](C)(C)C(C)(C)C)[C@H]3CC4=CC=C(O)C5=C4[C@@]2(CCN3CC2CCC2)[C@H]1O53294.6Semi standard non polar33892256
Nalbuphine,2TBDMS,isomer #2CC(C)(C)[Si](C)(C)OC1=CC=C2C[C@H]3N(CC4CCC4)CC[C@]45C2=C1O[C@H]4[C@@H](O[Si](C)(C)C(C)(C)C)CC[C@@]35O3363.1Semi standard non polar33892256
Nalbuphine,2TBDMS,isomer #3CC(C)(C)[Si](C)(C)OC1=CC=C2C[C@H]3N(CC4CCC4)CC[C@]45C2=C1O[C@H]4[C@@H](O)CC[C@@]35O[Si](C)(C)C(C)(C)C3354.9Semi standard non polar33892256
Nalbuphine,3TBDMS,isomer #1CC(C)(C)[Si](C)(C)OC1=CC=C2C[C@H]3N(CC4CCC4)CC[C@]45C2=C1O[C@H]4[C@@H](O[Si](C)(C)C(C)(C)C)CC[C@@]35O[Si](C)(C)C(C)(C)C3564.5Semi standard non polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Nalbuphine GC-MS (Non-derivatized) - 70eV, Positivesplash10-056u-9024000000-f340950b62bc62155aad2017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Nalbuphine GC-MS (3 TMS) - 70eV, Positivesplash10-0a6r-7200190000-d65993f303318329695e2017-10-06Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Nalbuphine GC-MS (TMS_2_3) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Nalbuphine GC-MS (TBDMS_2_3) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Nalbuphine GC-MS (TBDMS_3_1) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Nalbuphine GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Nalbuphine GC-MS ("Nalbuphine,2TMS,#3" TMS) - 70eV, PositiveNot Available2021-10-14Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental LC-MS/MSLC-MS/MS Spectrum - Nalbuphine 35V, Positive-QTOFsplash10-052f-0019000000-d9843432af7f0b68c1232021-09-20HMDB team, MONAView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nalbuphine 10V, Positive-QTOFsplash10-052f-2009000000-ebce756d2f09cd1910ab2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nalbuphine 20V, Positive-QTOFsplash10-014i-9007000000-bbd85f5711c7e46af99d2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nalbuphine 40V, Positive-QTOFsplash10-014i-9000000000-915ad990f371c4dabcfc2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nalbuphine 10V, Negative-QTOFsplash10-0a4i-0019000000-540f9874c968fbe7262c2016-08-04Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nalbuphine 20V, Negative-QTOFsplash10-052r-1039000000-aa9a27b2348aafb5a2e82016-08-04Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nalbuphine 40V, Negative-QTOFsplash10-05g3-3090000000-fe24dd502f436a5787fa2016-08-04Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nalbuphine 10V, Positive-QTOFsplash10-0a4i-0009000000-9957b000ea8c41ed82572021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nalbuphine 20V, Positive-QTOFsplash10-0a4i-0009000000-f48c8684121f5d183a1c2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nalbuphine 40V, Positive-QTOFsplash10-0zfr-0019000000-e87bebcd47bdb1e8e0a42021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nalbuphine 10V, Negative-QTOFsplash10-0a4i-0009000000-66d5ef9d584e1b0274e82021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nalbuphine 20V, Negative-QTOFsplash10-0a4i-0009000000-66d5ef9d584e1b0274e82021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Nalbuphine 40V, Negative-QTOFsplash10-0a4i-0019000000-3615de25291d9c20f0e32021-10-11Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00844 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00844 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00844
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID4470813
KEGG Compound IDC07251
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNalbuphine
METLIN IDNot Available
PubChem Compound5311304
PDB IDNot Available
ChEBI ID7454
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Gear RW, Miaskowski C, Gordon NC, Paul SM, Heller PH, Levine JD: The kappa opioid nalbuphine produces gender- and dose-dependent analgesia and antianalgesia in patients with postoperative pain. Pain. 1999 Nov;83(2):339-45. [PubMed:10534607 ]

Enzymes

General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Highly stereoselective. receptor for enkephalins
Gene Name:
OPRD1
Uniprot ID:
P41143
Molecular weight:
40412.3
References
  1. Chen JC, Smith ER, Cahill M, Cohen R, Fishman JB: The opioid receptor binding of dezocine, morphine, fentanyl, butorphanol and nalbuphine. Life Sci. 1993;52(4):389-96. [PubMed:8093631 ]
  2. De Souza EB, Schmidt WK, Kuhar MJ: Nalbuphine: an autoradiographic opioid receptor binding profile in the central nervous system of an agonist/antagonist analgesic. J Pharmacol Exp Ther. 1988 Jan;244(1):391-402. [PubMed:2826773 ]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for beta-endorphin
Gene Name:
OPRM1
Uniprot ID:
P35372
Molecular weight:
44778.9
References
  1. Kishioka S, Ko MC, Woods JH: Diltiazem enhances the analgesic but not the respiratory depressant effects of morphine in rhesus monkeys. Eur J Pharmacol. 2000 May 26;397(1):85-92. [PubMed:10844102 ]
  2. Hoehe M, Duka T: Opiates increase plasma catecholamines in humans. Psychoneuroendocrinology. 1993;18(2):141-8. [PubMed:8388112 ]
  3. Zernig G, Lewis JW, Woods JH: Clocinnamox inhibits the intravenous self-administration of opioid agonists in rhesus monkeys: comparison with effects on opioid agonist-mediated antinociception. Psychopharmacology (Berl). 1997 Feb;129(3):233-42. [PubMed:9084061 ]
  4. Picker MJ: Discriminative stimulus effects of the mixed-opioid agonist/antagonist dezocine: cross-substitution by mu and delta opioid agonists. J Pharmacol Exp Ther. 1997 Dec;283(3):1009-17. [PubMed:9399970 ]
  5. McNicol ED, Boyce D, Schumann R, Carr DB: Mu-opioid antagonists for opioid-induced bowel dysfunction. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD006332. doi: 10.1002/14651858.CD006332.pub2. [PubMed:18425947 ]
  6. Tao PL, Liang KW, Sung WY, Wu YT, Huang EY: Nalbuphine is effective in decreasing the rewarding effect induced by morphine in rats. Drug Alcohol Depend. 2006 Sep 15;84(2):175-81. Epub 2006 Mar 6. [PubMed:16517095 ]
  7. Smith MA, Greene-Naples JL, Lyle MA, Iordanou JC, Felder JN: The effects of repeated opioid administration on locomotor activity: I. Opposing actions of mu and kappa receptors. J Pharmacol Exp Ther. 2009 Aug;330(2):468-75. doi: 10.1124/jpet.108.150011. Epub 2009 Apr 29. [PubMed:19403853 ]
  8. Mello NK, Mendelson JH, Sholar MB, Jaszyna-Gasior M, Goletiani N, Siegel AJ: Effects of the mixed mu/kappa opioid nalbuphine on cocaine-induced changes in subjective and cardiovascular responses in men. Neuropsychopharmacology. 2005 Mar;30(3):618-32. [PubMed:15602503 ]
  9. Meerpohl JJ, Timmer A: [News from the cochrane library: mu opioid antagonists for opioid-induced bowel dysfunction]. Z Gastroenterol. 2008 Sep;46(9):917-21. doi: 10.1055/s-2008-1027720. Epub 2008 Sep 22. [PubMed:18810678 ]
  10. Peng X, Knapp BI, Bidlack JM, Neumeyer JL: Pharmacological properties of bivalent ligands containing butorphan linked to nalbuphine, naltrexone, and naloxone at mu, delta, and kappa opioid receptors. J Med Chem. 2007 May 3;50(9):2254-8. Epub 2007 Apr 4. [PubMed:17407276 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
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
Gene Name:
OPRK1
Uniprot ID:
P41145
Molecular weight:
42644.7
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: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. [PubMed:17016423 ]
  3. Hoehe M, Duka T: Opiates increase plasma catecholamines in humans. Psychoneuroendocrinology. 1993;18(2):141-8. [PubMed:8388112 ]
  4. Chen SL, Huang EY, Chow LH, Tao PL: Dextromethorphan differentially affects opioid antinociception in rats. Br J Pharmacol. 2005 Feb;144(3):400-4. [PubMed:15655510 ]
  5. Tao PL, Liang KW, Sung WY, Wu YT, Huang EY: Nalbuphine is effective in decreasing the rewarding effect induced by morphine in rats. Drug Alcohol Depend. 2006 Sep 15;84(2):175-81. Epub 2006 Mar 6. [PubMed:16517095 ]
  6. Smith MA, Greene-Naples JL, Lyle MA, Iordanou JC, Felder JN: The effects of repeated opioid administration on locomotor activity: I. Opposing actions of mu and kappa receptors. J Pharmacol Exp Ther. 2009 Aug;330(2):468-75. doi: 10.1124/jpet.108.150011. Epub 2009 Apr 29. [PubMed:19403853 ]
  7. Mello NK, Mendelson JH, Sholar MB, Jaszyna-Gasior M, Goletiani N, Siegel AJ: Effects of the mixed mu/kappa opioid nalbuphine on cocaine-induced changes in subjective and cardiovascular responses in men. Neuropsychopharmacology. 2005 Mar;30(3):618-32. [PubMed:15602503 ]
  8. Gear RW, Miaskowski C, Gordon NC, Paul SM, Heller PH, Levine JD: The kappa opioid nalbuphine produces gender- and dose-dependent analgesia and antianalgesia in patients with postoperative pain. Pain. 1999 Nov;83(2):339-45. [PubMed:10534607 ]
  9. Peng X, Knapp BI, Bidlack JM, Neumeyer JL: Pharmacological properties of bivalent ligands containing butorphan linked to nalbuphine, naltrexone, and naloxone at mu, delta, and kappa opioid receptors. J Med Chem. 2007 May 3;50(9):2254-8. Epub 2007 Apr 4. [PubMed:17407276 ]