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Reboxetine
Identification
- Name
- Reboxetine
- Accession Number
- DB00234
- 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.
- Type
- Small Molecule
- Groups
- Approved, Experimental
- Structure
Structure for Reboxetine (DB00234)
- Weight
- Average: 313.397
Monoisotopic: 313.167793605 - Chemical Formula
- C19H23NO3
- Synonyms
- Reboxetina
Pharmacology
- Indication
For the treatment of clinical depression.
- Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More- Pharmacodynamics
Reboxetine 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 action
Reboxetine 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.
Target Actions Organism ASodium-dependent noradrenaline transporter inhibitorHumans - Absorption
Reboxetine is rapidly and extensively absorbed following oral administration.
- Volume of distribution
- Not Available
- Protein binding
98%
- 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 elimination
- Not Available
- Half-life
12.5 hours
- Clearance
- Not Available
- Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More- Toxicity
Reports of seizures (rare) have been reported
- Affected organisms
- Humans and other mammals
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Unlock Additional DataAbametapir The serum concentration of Reboxetine can be increased when it is combined with Abametapir. Acebutolol The metabolism of Acebutolol can be decreased when combined with Reboxetine. Acenocoumarol The risk or severity of adverse effects can be increased when Reboxetine is combined with Acenocoumarol. Acetaminophen The metabolism of Acetaminophen can be decreased when combined with Reboxetine. Acetazolamide The risk or severity of adverse effects can be increased when Reboxetine is combined with Acetazolamide. Acetophenazine The risk or severity of adverse effects can be increased when Reboxetine is combined with Acetophenazine. Aclidinium Reboxetine may increase the central nervous system depressant (CNS depressant) activities of Aclidinium. Agomelatine The risk or severity of adverse effects can be increased when Reboxetine is combined with Agomelatine. Alfentanil The risk or severity of adverse effects can be increased when Reboxetine is combined with Alfentanil. Alimemazine The risk or severity of adverse effects can be increased when Reboxetine is combined with Alimemazine. Additional Data Available- Extended DescriptionExtended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
Learn more - Severity
- Evidence Level
- ActionAction
An effect category for each drug interaction. Know how this interaction affects the subject drug.
Learn more
- Food Interactions
- Not Available
Products
- Product Ingredients
Ingredient UNII CAS InChI Key Reboxetine mesilate L94J81YNNY 98769-84-7 CGTZMJIMMUNLQD-STYNFMPRSA-N - International/Other Brands
- Davedax / Edronax / Norebox / Prolift / Solvex / Vestra
Categories
- ATC Codes
- N06AX18 — Reboxetine
- Drug Categories
- Adrenergic Agents
- Adrenergic Uptake Inhibitors
- Antidepressive Agents
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (weak)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Membrane Transport Modulators
- Morpholines
- Nervous System
- Neurotransmitter Agents
- Neurotransmitter Uptake Inhibitors
- Oxazines
- P-glycoprotein inhibitors
- Psychoanaleptics
- Psychotropic Drugs
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Phenol ethers
- Sub Class
- Not Available
- Direct Parent
- Phenol ethers
- Alternative Parents
- Phenoxy compounds / Aralkylamines / Alkyl aryl ethers / Morpholines / Oxacyclic compounds / Dialkylamines / Dialkyl ethers / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- Alkyl aryl ether / Amine / Aralkylamine / Aromatic heteromonocyclic compound / Azacycle / Dialkyl ether / Ether / Hydrocarbon derivative / Monocyclic benzene moiety / Morpholine
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
Chemical Identifiers
- UNII
- 947S0YZ36I
- CAS number
- 71620-89-8
- InChI Key
- CBQGYUDMJHNJBX-RTBURBONSA-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-/m1/s1
- IUPAC Name
- (2R)-2-[(R)-(2-ethoxyphenoxy)(phenyl)methyl]morpholine
- SMILES
- [H][C@@](OC1=CC=CC=C1OCC)(C1=CC=CC=C1)[C@@]1([H])CNCCO1
References
- General References
- 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]
- 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]
- 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]
- 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]
- External Links
- PubChem Compound
- 127151
- PubChem Substance
- 46504845
- ChemSpider
- 112870
- 60842
- ChEBI
- 135342
- ChEMBL
- CHEMBL383921
- ZINC
- ZINC000003996032
- Therapeutic Targets Database
- DAP000720
- PharmGKB
- PA144614921
- PDBe Ligand
- 41X
- Wikipedia
- Reboxetine
- PDB Entries
- 4xnx
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Cerebral Stroke 1 4 Unknown Status Treatment Abdominal Pain / Major Depressive Disorder (MDD) / Pain 1 4 Unknown Status Treatment Depression 1 4 Unknown Status Treatment Schizophrenia 1 3 Completed Supportive Care Bone Mineral Density Quantitative Trait Locus 7 1 3 Completed Treatment Fibromyalgia 1 3 Terminated Treatment Anxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenia 1 3 Terminated Treatment Fibromyalgia 2 2 Completed Treatment Cataplexy Narcolepsy / Narcolepsy / Somnolence 1 2 Completed Treatment Major Depressive Disorder (MDD) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 170-171 °C (Mesylate salt) Not Available water solubility 8 mg/mL (Mesylate salt) Not Available logP 3.1 Not Available - Predicted Properties
Property Value Source Water Solubility 0.0223 mg/mL ALOGPS logP 3.06 ALOGPS logP 3.28 ChemAxon logS -4.2 ALOGPS pKa (Strongest Basic) 7.91 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 4 ChemAxon Hydrogen Donor Count 1 ChemAxon Polar Surface Area 39.72 Å2 ChemAxon Rotatable Bond Count 6 ChemAxon Refractivity 89.48 m3·mol-1 ChemAxon Polarizability 34.51 Å3 ChemAxon Number of Rings 3 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule Yes ChemAxon MDDR-like Rule Yes ChemAxon - 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 inhibitor Non-inhibitor 0.8063 CYP450 2D6 inhibitor Non-inhibitor 0.5687 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor 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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- 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
- Uniprot Name
- Sodium-dependent noradrenaline transporter
- Molecular Weight
- 69331.42 Da
References
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Vitamin d3 25-hydroxylase 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 react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Kuhn UD, Kirsch M, Merkel U, Eberhardt AM, Wenda B, Maurer I, Hartter S, Hiemke C, Volz HP, Balogh A: Reboxetine and cytochrome P450--comparison with paroxetine treatment in humans. Int J Clin Pharmacol Ther. 2007 Jan;45(1):36-46. doi: 10.5414/cpp45036. [PubMed:17256449]
- 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]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase 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...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- 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]
- Kuhn UD, Kirsch M, Merkel U, Eberhardt AM, Wenda B, Maurer I, Hartter S, Hiemke C, Volz HP, Balogh A: Reboxetine and cytochrome P450--comparison with paroxetine treatment in humans. Int J Clin Pharmacol Ther. 2007 Jan;45(1):36-46. doi: 10.5414/cpp45036. [PubMed:17256449]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- 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]
Drug created on June 13, 2005 07:24 / Updated on July 02, 2020 07:27
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