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Identification
NameReboxetine
Accession NumberDB00234  (APRD00198)
Typesmall molecule
Groupsapproved, investigational
Description

Reboxetine 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
Thumb
Synonyms
SynonymLanguageCode
(SNot AvailableNot Available
EsreboxetineNot AvailableNot Available
ReboxetineNot AvailableNot Available
S)-ReboxetineNot AvailableNot Available
SID11114256Not AvailableNot Available
Salts
Name/CAS Structure Properties
Reboxetine methanesulfonate
Thumb Not applicable DBSALT000890
Brand names
NameCompany
DavedaxNot Available
EdronaxNot Available
NoreboxNot Available
ProliftNot Available
SolvexNot Available
VestraNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number98769-81-4
WeightAverage: 313.3908
Monoisotopic: 313.167793607
Chemical FormulaC19H23NO3
InChI KeyCBQGYUDMJHNJBX-OALUTQOASA-N
InChI
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
IUPAC Name
(2S)-2-[(S)-2-ethoxyphenoxy(phenyl)methyl]morpholine
SMILES
[H][C@]1(CNCCO1)[C@@H](OC1=CC=CC=C1OCC)C1=CC=CC=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzylethers
Direct parentBenzylethers
Alternative parentsPhenol Ethers; Alkyl Aryl Ethers; Morpholines; Dialkylamines; Polyamines
Substituentsphenol ether; alkyl aryl ether; oxazinane; morpholine; secondary aliphatic amine; ether; secondary amine; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the benzylethers. These are aromatic ethers with the general formula ROCR' (R = alkyl, aryl; R'=benzene).
Pharmacology
IndicationFor the treatment of clinical depression.
PharmacodynamicsReboxetine is a selective noradrenaline reuptake inhibitor (NaRI), the first drug of new antidepressant class. Reboxetine is an a-ariloxybenzyl derivative of morpholine. Reboxetine is primarily used to treat depression but has also been found useful in the treatment of narcolepsy and panic disorders.
Mechanism of actionReboxetine 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.
AbsorptionReboxetine is rapidly and extensively absorbed following oral administration.
Volume of distributionNot Available
Protein binding98%
Metabolism

Reboxetine is metabolized by dealkylation, hydroxylation and oxidation followed by glucuronide or sulphate conjugation. It is metabolized by the cytochrome P450 CYP isoenzyme 3A4.

Route of eliminationNot Available
Half life12.5 hours
ClearanceNot Available
ToxicityReports of seizures (rare) have been reported
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9968
Blood Brain Barrier + 0.9381
Caco-2 permeable + 0.575
P-glycoprotein substrate Substrate 0.7914
P-glycoprotein inhibitor I Inhibitor 0.8825
P-glycoprotein inhibitor II Non-inhibitor 0.5968
Renal organic cation transporter Non-inhibitor 0.5581
CYP450 2C9 substrate Non-substrate 0.8237
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Non-substrate 0.5402
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.8063
CYP450 2D6 substrate Non-inhibitor 0.5687
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Inhibitor 0.6318
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5218
Ames test Non AMES toxic 0.9141
Carcinogenicity Non-carcinogens 0.9083
Biodegradation Not ready biodegradable 0.9372
Rat acute toxicity 2.0972 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Strong inhibitor 0.7754
hERG inhibition (predictor II) Inhibitor 0.717
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point170-171 °C (Mesylate salt)Not Available
water solubility8 mg/mL (Mesylate salt)Not Available
logP3.1Not Available
Predicted Properties
PropertyValueSource
water solubility2.23e-02 g/lALOGPS
logP3.06ALOGPS
logP3.28ChemAxon
logS-4.2ALOGPS
pKa (strongest basic)7.91ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count1ChemAxon
polar surface area39.72ChemAxon
rotatable bond count6ChemAxon
refractivity89.48ChemAxon
polarizability34.17ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  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. Pubmed
  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
  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
  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. Pubmed
  5. 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
External Links
ResourceLink
PubChem Compound65856
PubChem Substance46504845
ChemSpider59268
BindingDB35226
Therapeutic Targets DatabaseDAP000720
PharmGKBPA144614921
WikipediaReboxetine
ATC CodesN06AX18
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Sodium-dependent noradrenaline transporter

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium-dependent noradrenaline transporter P23975 Details

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
  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
  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
  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
  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
  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

Enzymes

1. 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

2. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor inducer

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

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

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

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Drug created on June 13, 2005 07:24 / Updated on September 25, 2013 14:57