Reboxetine

Identification

Name

Reboxetine

Accession Number

DB00234  (APRD00198)

Type

Small Molecule

Groups

Approved, Experimental

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

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Reboxetine (DB00234)

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Synonyms

• Reboxetina

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

• 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

UNII

947S0YZ36I

CAS number

71620-89-8

Weight

Average: 313.397
Monoisotopic: 313.167793605

Chemical Formula

C₁₉H₂₃NO₃

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

Pharmacology

Indication

For the treatment of clinical depression.

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	inhibitor	Humans

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

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.

• All Drugs
• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental

Drug	Interaction
Unlock Additional Data
(R)-warfarin	The risk or severity of adverse effects can be increased when Reboxetine is combined with (R)-warfarin.
(S)-Warfarin	The risk or severity of adverse effects can be increased when Reboxetine is combined with (S)-Warfarin.
2,5-Dimethoxy-4-ethylthioamphetamine	The risk or severity of adverse effects can be increased when Reboxetine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
4-Bromo-2,5-dimethoxyamphetamine	The risk or severity of adverse effects can be increased when Reboxetine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarin	The risk or severity of adverse effects can be increased when Reboxetine is combined with 4-hydroxycoumarin.
4-Methoxyamphetamine	The risk or severity of adverse effects can be increased when Reboxetine is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamine	The risk or severity of adverse effects can be increased when Reboxetine is combined with 5-methoxy-N,N-dimethyltryptamine.
7-Nitroindazole	The risk or severity of adverse effects can be increased when Reboxetine is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline	The risk or severity of adverse effects can be increased when Reboxetine is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
Acebutolol	The metabolism of Acebutolol can be decreased when combined with Reboxetine.

Additional Data Available

Extended Description
Extended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
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Severity
Severity
A severity rating for each drug interaction, from minor to major.
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Evidence Level
Evidence Level
A rating for the strength of the evidence supporting each drug interaction.
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Action
Action
An effect category for each drug interaction. Know how this interaction affects the subject drug.
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Food Interactions

Not Available

References

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. [PubMed: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. [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. 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

RxNav

60842

ChEBI

135342

ChEMBL

CHEMBL383921

ZINC

ZINC000003996032

Therapeutic Targets Database

DAP000720

PharmGKB

PA144614921

PDBe Ligand

41X

Wikipedia

Reboxetine

ATC Codes

N06AX18 — Reboxetine

• N06AX — Other antidepressants
• N06A — ANTIDEPRESSANTS
• N06 — PSYCHOANALEPTICS
• N — NERVOUS SYSTEM

PDB Entries

4xnx

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1	Completed	Basic Science	Amphetamine-Related Disorders / Moods Disorders / Substance-Related Disorders	1
1	Recruiting	Treatment	Fecal Incontinence / Stress Urinary Incontinence (SUI)	1
1	Unknown Status	Treatment	Schizophrenia	1
2	Completed	Treatment	Cataplexy Narcolepsy / Narcolepsy / Somnolence	1
2	Completed	Treatment	Major Depressive Disorder (MDD)	1
2	Completed	Treatment	Pain	3
2	Terminated	Treatment	Diabetic Neuropathies	1
2	Terminated	Treatment	Pain	4
2	Withdrawn	Treatment	Attention Deficit Disorder With Hyperactivity (ADHD)	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
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
Not Available	Completed	Basic Science	Cognitive Performance in Major Depression	1
Not Available	Completed	Treatment	Healthy Volunteers	1
Not Available	Completed	Treatment	Major Depressive Disorder (MDD)	1
Not Available	Not Yet Recruiting	Basic Science	Healthy Volunteers	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

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

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

Taxonomy

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

Phenoxy compound / Phenol ether / Alkyl aryl ether / Aralkylamine / Monocyclic benzene moiety / Morpholine / Oxazinane / Dialkyl ether / Secondary aliphatic amine / Ether

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

Not Available

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Drug created on June 13, 2005 07:24 / Updated on March 01, 2020 23:20