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Record Information
Version2.0
Creation Date2009-07-21 20:26:21 UTC
Update Date2014-12-24 20:25:50 UTC
Accession NumberT3D2720
Identification
Common NameReboxetine
ClassSmall Molecule
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.
Compound Type
  • Adrenergic Uptake Inhibitor
  • Amine
  • Antidepressant
  • Drug
  • Ether
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(S
Davedax
Edronax
Esreboxetine
Norebox
Prolift
Reboxetine mesylate
S)-Reboxetine
Solvex
Vestra
Chemical FormulaC19H23NO3
Average Molecular Mass313.391 g/mol
Monoisotopic Mass313.168 g/mol
CAS Registry Number98769-81-4
IUPAC Name(2S)-2-[(S)-2-ethoxyphenoxy(phenyl)methyl]morpholine
Traditional Namereboxetine
SMILES[H][C@](OC1=CC=CC=C1OCC)(C1=CC=CC=C1)[C@]1([H])CNCCO1
InChI IdentifierInChI=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 KeyInChIKey=CBQGYUDMJHNJBX-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
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point170-171°C (Mesylate salt)
Boiling PointNot Available
Solubility8 mg/mL (Mesylate salt)
LogP3.1
Predicted 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
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-002f-9510000000-c419747ac13882d22181JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0129000000-8a66fcd9f27a2e8d1e29JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0h6r-1391000000-293a0b61cefb20d06e3dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-05r3-9500000000-725ea11aada64c859bc4JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-1249000000-0355482034f887fdfb23JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03el-2693000000-66480f21ca5998c6d03cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4l-7900000000-b34a81b04900dc0e1282JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0709000000-49770d96ddc33f490da6JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-01tc-6912000000-89667ca9f247b109629aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-002f-9600000000-500dfce79cc2fe29db26JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0319000000-650b49e0d4835471204cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-0900000000-0085228a23971030ec0aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-4911000000-5c78e43b439b2c360e21JSpectraViewer
Toxicity Profile
Route of ExposureReboxetine is rapidly and extensively absorbed following oral administration.
Mechanism of ToxicityReboxetine is a selective inhibitor of noradrenaline reuptake. It inhibits noradrenaline reuptake in vitro to a similar extent to the tricyclic antidepressant desmethylimipramine. Reboxetine does not affect dopamine or serotonin reuptake and it has low in vivo and in vitro affinity for adrenergic, cholinergic, histaminergic, dopaminergic and serotonergic receptors.
MetabolismReboxetine is metabolized by dealkylation, hydroxylation and oxidation followed by glucuronide or sulphate conjugation. It is metabolized by the cytochrome P450 CYP isoenzyme 3A4. Half Life: 12.5 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of clinical depression.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsReports of seizures (rare) have been reported
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00234
HMDB IDHMDB14379
PubChem Compound ID65856
ChEMBL IDCHEMBL14370
ChemSpider ID59268
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID402799
BioCyc IDNot Available
CTD IDNot Available
Stitch IDReboxetine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkReboxetine
References
Synthesis ReferenceNot Available
MSDST3D2720.pdf
General References
  1. 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. [11192474 ]
  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. [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. [10534319 ]
  4. Kasper S, el Giamal N, Hilger E: Reboxetine: the first selective noradrenaline re-uptake inhibitor. Expert Opin Pharmacother. 2000 May;1(4):771-82. [11249515 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Norepinephrine: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 Da
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. [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. [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. [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. [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. [16893531 ]