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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:49 UTC
Update Date2022-03-07 02:51:36 UTC
HMDB IDHMDB0014379
Secondary Accession Numbers
  • HMDB14379
Metabolite Identification
Common NameReboxetine
DescriptionReboxetine is an antidepressant drug used in the treatment of clinical depression, panic disorder and ADD/ADHD. Its mesylate (i.e. methanesulfonate) salt is sold under tradenames including Edronax, Norebox, Prolift, Solvex, Davedax or Vestra. Reboxetine has two chiral centers, but it only exists as two enantiomers, (R,R)-(-)- and (S,S)-(+)-reboxetine.
Structure
Data?1582753172
Synonyms
ValueSource
(SS)-ReboxetineHMDB
Reboxetine mesylateHMDB
2-((2-Ethoxyphenoxy)benzyl)morpholine methanesulfonateHMDB
VestraHMDB
(+)-(2S)-2-((S)-(2-Ethoxyphenoxy)phenylmethyl)morpholineHMDB
ReboxetineMeSH
Chemical FormulaC19H23NO3
Average Molecular Weight313.3908
Monoisotopic Molecular Weight313.167793607
IUPAC Name(2S)-2-[(S)-2-ethoxyphenoxy(phenyl)methyl]morpholine
Traditional Namereboxetine
CAS Registry Number98769-81-4
SMILES
[H][C@]1(CNCCO1)[C@@H](OC1=CC=CC=C1OCC)C1=CC=CC=C1
InChI Identifier
InChI=1S/C19H23NO3/c1-2-21-16-10-6-7-11-17(16)23-19(15-8-4-3-5-9-15)18-14-20-12-13-22-18/h3-11,18-20H,2,12-14H2,1H3/t18-,19-/m0/s1
InChI KeyCBQGYUDMJHNJBX-OALUTQOASA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassPhenol ethers
Sub ClassNot Available
Direct ParentPhenol ethers
Alternative Parents
Substituents
  • Phenoxy compound
  • Phenol ether
  • Alkyl aryl ether
  • Aralkylamine
  • Monocyclic benzene moiety
  • Morpholine
  • Oxazinane
  • Dialkyl ether
  • Secondary aliphatic amine
  • Ether
  • Oxacycle
  • Secondary amine
  • Organoheterocyclic compound
  • Azacycle
  • Organopnictogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic oxygen compound
  • Organic nitrogen compound
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Ontology
Not AvailableNot Available
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting Point170 - 171 °C (mesylate salt)Not Available
Boiling PointNot AvailableNot Available
Water Solubility0.022 g/LNot Available
LogP3.1Not Available
Experimental Chromatographic Properties

Experimental Collision Cross Sections

Adduct TypeData SourceCCS Value (Å2)Reference
[M+H]+CBM174.030932474
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.022 g/LALOGPS
logP3.06ALOGPS
logP3.28ChemAxon
logS-4.2ALOGPS
pKa (Strongest Basic)7.91ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area39.72 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity89.48 m³·mol⁻¹ChemAxon
Polarizability34.17 ųChemAxon
Number of Rings3ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DarkChem[M+H]+174.27431661259
DarkChem[M-H]-174.47231661259
DeepCCS[M+H]+172.3530932474
DeepCCS[M-H]-169.99230932474
DeepCCS[M-2H]-203.58230932474
DeepCCS[M+Na]+178.8130932474
AllCCS[M+H]+176.032859911
AllCCS[M+H-H2O]+172.632859911
AllCCS[M+NH4]+179.132859911
AllCCS[M+Na]+180.032859911
AllCCS[M-H]-179.632859911
AllCCS[M+Na-2H]-179.332859911
AllCCS[M+HCOO]-179.132859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
Reboxetine[H][C@]1(CNCCO1)[C@@H](OC1=CC=CC=C1OCC)C1=CC=CC=C12982.2Standard polar33892256
Reboxetine[H][C@]1(CNCCO1)[C@@H](OC1=CC=CC=C1OCC)C1=CC=CC=C12431.1Standard non polar33892256
Reboxetine[H][C@]1(CNCCO1)[C@@H](OC1=CC=CC=C1OCC)C1=CC=CC=C12372.2Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Reboxetine,1TMS,isomer #1CCOC1=CC=CC=C1O[C@@H](C1=CC=CC=C1)[C@@H]1CN([Si](C)(C)C)CCO12462.4Semi standard non polar33892256
Reboxetine,1TMS,isomer #1CCOC1=CC=CC=C1O[C@@H](C1=CC=CC=C1)[C@@H]1CN([Si](C)(C)C)CCO12438.0Standard non polar33892256
Reboxetine,1TMS,isomer #1CCOC1=CC=CC=C1O[C@@H](C1=CC=CC=C1)[C@@H]1CN([Si](C)(C)C)CCO13361.9Standard polar33892256
Reboxetine,1TBDMS,isomer #1CCOC1=CC=CC=C1O[C@@H](C1=CC=CC=C1)[C@@H]1CN([Si](C)(C)C(C)(C)C)CCO12689.3Semi standard non polar33892256
Reboxetine,1TBDMS,isomer #1CCOC1=CC=CC=C1O[C@@H](C1=CC=CC=C1)[C@@H]1CN([Si](C)(C)C(C)(C)C)CCO12620.6Standard non polar33892256
Reboxetine,1TBDMS,isomer #1CCOC1=CC=CC=C1O[C@@H](C1=CC=CC=C1)[C@@H]1CN([Si](C)(C)C(C)(C)C)CCO13477.0Standard polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Reboxetine GC-MS (Non-derivatized) - 70eV, Positivesplash10-002f-9510000000-c419747ac13882d221812017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Reboxetine GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Reboxetine GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Reboxetine 10V, Positive-QTOFsplash10-03di-0129000000-8a66fcd9f27a2e8d1e292017-07-25Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Reboxetine 20V, Positive-QTOFsplash10-0h6r-1391000000-293a0b61cefb20d06e3d2017-07-25Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Reboxetine 40V, Positive-QTOFsplash10-05r3-9500000000-725ea11aada64c859bc42017-07-25Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Reboxetine 10V, Negative-QTOFsplash10-03di-1249000000-0355482034f887fdfb232017-07-26Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Reboxetine 20V, Negative-QTOFsplash10-03el-2693000000-66480f21ca5998c6d03c2017-07-26Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Reboxetine 40V, Negative-QTOFsplash10-0a4l-7900000000-b34a81b04900dc0e12822017-07-26Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Reboxetine 10V, Positive-QTOFsplash10-03di-0709000000-49770d96ddc33f490da62021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Reboxetine 20V, Positive-QTOFsplash10-01tc-6912000000-89667ca9f247b109629a2021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Reboxetine 40V, Positive-QTOFsplash10-002f-9600000000-500dfce79cc2fe29db262021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Reboxetine 10V, Negative-QTOFsplash10-03di-0319000000-650b49e0d4835471204c2021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Reboxetine 20V, Negative-QTOFsplash10-0a4i-0900000000-0085228a23971030ec0a2021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Reboxetine 40V, Negative-QTOFsplash10-0a4i-4911000000-5c78e43b439b2c360e212021-09-22Wishart 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 DB00234 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00234 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 IDDB12395
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID59268
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkReboxetine
METLIN IDNot Available
PubChem Compound65856
PDB IDNot Available
ChEBI ID402799
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. Kasper S, el Giamal N, Hilger E: Reboxetine: the first selective noradrenaline re-uptake inhibitor. Expert Opin Pharmacother. 2000 May;1(4):771-82. [PubMed:11249515 ]
  2. Edwards DM, Pellizzoni C, Breuel HP, Berardi A, Castelli MG, Frigerio E, Poggesi I, Rocchetti M, Dubini A, Strolin Benedetti M: Pharmacokinetics of reboxetine in healthy volunteers. Single oral doses, linearity and plasma protein binding. Biopharm Drug Dispos. 1995 Aug;16(6):443-60. [PubMed:7579027 ]
  3. Wienkers LC, Allievi C, Hauer MJ, Wynalda MA: Cytochrome P-450-mediated metabolism of the individual enantiomers of the antidepressant agent reboxetine in human liver microsomes. Drug Metab Dispos. 1999 Nov;27(11):1334-40. [PubMed:10534319 ]
  4. Fleishaker JC: Clinical pharmacokinetics of reboxetine, a selective norepinephrine reuptake inhibitor for the treatment of patients with depression. Clin Pharmacokinet. 2000 Dec;39(6):413-27. [PubMed:11192474 ]

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in monooxygenase 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
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
References
  1. Weiss J, Dormann SM, Martin-Facklam M, Kerpen CJ, Ketabi-Kiyanvash N, Haefeli WE: Inhibition of P-glycoprotein by newer antidepressants. J Pharmacol Exp Ther. 2003 Apr;305(1):197-204. [PubMed:12649369 ]
General function:
Involved in neurotransmitter:sodium symporter activity
Specific function:
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A2
Uniprot ID:
P23975
Molecular weight:
69331.42
References
  1. Rauhut AS, Mullins SN, Dwoskin LP, Bardo MT: Reboxetine: attenuation of intravenous nicotine self-administration in rats. J Pharmacol Exp Ther. 2002 Nov;303(2):664-72. [PubMed:12388649 ]
  2. Wilson AA, Johnson DP, Mozley D, Hussey D, Ginovart N, Nobrega J, Garcia A, Meyer J, Houle S: Synthesis and in vivo evaluation of novel radiotracers for the in vivo imaging of the norepinephrine transporter. Nucl Med Biol. 2003 Feb;30(2):85-92. [PubMed:12623106 ]
  3. Lin KS, Ding YS, Kim SW, Kil KE: Synthesis, enantiomeric resolution, F-18 labeling and biodistribution of reboxetine analogs: promising radioligands for imaging the norepinephrine transporter with positron emission tomography. Nucl Med Biol. 2005 May;32(4):415-22. [PubMed:15878511 ]
  4. Spivak B, Strous RD, Shaked G, Shabash E, Kotler M, Weizman A: Reboxetine versus fluvoxamine in the treatment of motor vehicle accident-related posttraumatic stress disorder: a double-blind, fixed-dosage, controlled trial. J Clin Psychopharmacol. 2006 Apr;26(2):152-6. [PubMed:16633143 ]
  5. Mitchell HA, Ahern TH, Liles LC, Javors MA, Weinshenker D: The effects of norepinephrine transporter inactivation on locomotor activity in mice. Biol Psychiatry. 2006 Nov 15;60(10):1046-52. Epub 2006 Aug 7. [PubMed:16893531 ]
  6. Kasper S, el Giamal N, Hilger E: Reboxetine: the first selective noradrenaline re-uptake inhibitor. Expert Opin Pharmacother. 2000 May;1(4):771-82. [PubMed:11249515 ]