Identification

Summary

Viloxazine is a selective norepinephrine reuptake inhibitor indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in adults in children.

Brand Names
Qelbree
Generic Name
Viloxazine
DrugBank Accession Number
DB09185
Background

Viloxazine is a selective norepinephrine reuptake inhibitor.7 For decades, an immediate-release formulation of viloxazine has been used in Europe as an antidepressant. It was first approved in the UK in 1974; however, the immediate-release formulation was discontinued due to business reasons unrelated to drug safety and efficacy. In the US, viloxazine was assigned an orphan drug designation in 1984 under the brand name CATATROL: while this product was intended to treat cataplexy and narcolepsy, the drug was never approved for these therapeutic indications. In April 2021, an extended-release formulation of viloxazine under the brand name QELBREE was approved by the FDA for the treatment of attention deficit hyperactivity disorder (ADHD).6

Type
Small Molecule
Groups
Approved, Investigational, Withdrawn
Structure
Weight
Average: 237.299
Monoisotopic: 237.136493476
Chemical Formula
C13H19NO3
Synonyms
  • 2-((2-Ethoxyphenoxy)methyl)morpholine
  • Viloxazina
  • Viloxazine
  • Viloxazinum

Pharmacology

Indication

Viloxazine is a selective norepinephrine reuptake inhibitor indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in adults and pediatric patients 6 years and older.7

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Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Viloxazine is a serotonin-norepinephrine modulating agent that has been used as a treatment for depression and Attention Deficit Hyperactivity Disorder (ADHD).6 Although it is not a stimulant agent, viloxazine produces amphetamine-like CNS stimulant effects without a risk for drug abuse or dependence.4 Viloxazine does not produce sedative anticholinergic or adrenergic effects.1,4

Mechanism of action

Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder in children characterized by inattention and hyperactivity. In current literature, the pathophysiology of ADHD is understood to involve the imbalance of neurotransmitters, especially dopamine (DA) and norepinephrine (NE).4 The mechanism of action of viloxazine has not been fully elucidated; however, viloxazine is believed to work by modulating the monoaminergic neurotransmitter systems. Viloxazine is a selective and moderate norepinephrine reuptake inhibitor that binds to the norepinephrine transporter and inhibits the reuptake of norepinephrine.6,7 It thereby increases extracellular norepinephrine levels across several brain regions.6

Viloxazine potentiates serotonergic effects: it was shown to enhance neuronal sensitivity to serotonin and increase serotonin levels in the brain.5,6 In vitro, viloxazine is an antagonist at 5-HT2B receptors and an agonist 5-HT2C receptors.4,5 5-HT2B receptors expressed on GABAergic interneurons are involved in tonic inhibitory control of serotonin neurons that innervate the medial prefrontal context; thus, antagonism of 5-HT2B receptors may result in disinhibition and enhanced serotonin release in the brain region.6

There is conflicting evidence in the literature that viloxazine increases dopamine levels in the brain via direct or indirect effects. For example, the norepinephrine transporter is also involved in the reuptake of dopamine in the prefrontal cortex 6 and stimulation of 5-HT2C receptors facilitates DA release and enhances dopaminergic transmission in the brain.5 As dopamine dysregulation in the prefrontal cortex and amygdala is implicated in ADHD pathophysiology, the impact of viloxazine on dopamine levels may contribute to its mechanism of action. However, there is insufficient evidence to conclude this. Viloxazine has a negligible impact on dopamine in the nucleus accumbens and is not associated with an abuse risk.6

TargetActionsOrganism
ASodium-dependent noradrenaline transporter
inhibitor
Humans
A5-hydroxytryptamine receptor 2B
antagonist
Humans
A5-hydroxytryptamine receptor 2C
agonist
Humans
UAlpha-1B adrenergic receptor
antagonist
Humans
UBeta-2 adrenergic receptor
antagonist
Humans
UHistamine H1 receptor
antagonist
Humans
UHistamine H2 receptor
antagonist
Humans
UMuscarinic acetylcholine receptor M1
antagonist
Humans
UMuscarinic acetylcholine receptor M2
antagonist
Humans
UMuscarinic acetylcholine receptor M3
antagonist
Humans
UMuscarinic acetylcholine receptor M4
antagonist
Humans
UAmine oxidase [flavin-containing] A
inhibitor
Humans
UAmine oxidase [flavin-containing] B
inhibitor
Humans
Absorption

Viloxazine is rapidly absorbed following oral administration.1,2 The relative bioavailability of viloxazine extended-release relative to an immediate-release formulation was about 88%.7

Viloxazine Cmax and AUC increase proportionally over a dosage range from 100 mg to 600 mg once daily.7 The Cmax ranges between 540 and 1600 ng/mL.1 Following administration of a single 200 mg dose, the median Tmax was approximately five hours, with a range of three to nine hours. Steady-state was reached after two days of once-daily administration, and no accumulation was observed. A high-fat meal decreases Cmax and AUC by about 9% and 8%, respectively, and delays Tmax by two hours.7

Volume of distribution

The volume of distribution was 0.73 ± 0.28 L/kg following intravenous administration.6

Protein binding

Viloxazine is 76-82% bound to human plasma proteins over the blood concentration range of 0.5 mcg/mL to 10 mcg/mL.7

Metabolism

Viloxazine undergoes CYP2D6-mediated 5-hydroxylation to form 5-hydroxyviloxazine. This metabolite can be glucuronidated by UGT1A9 and UGT2B15 to form 5-hydroxyviloxazine glucuronide,3 which is the major metabolite detected in plasma.7 Viloxazine can also be glucuronidated to form Viloxazine N-carbamoyl glucuronide.3

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Route of elimination

Viloxazine is primarily excreted via renal elimination. After administration of radiolabeled viloxazine, 90% of the dose was recovered in urine within the first 24 hours post-dose. Less than 1% of the dose is excreted in the feces.7 About 12-15% of the total drug is eliminated as unchanged parent drug.1

Half-life

The mean (± SD) half-life of viloxazine was 7.02 (± 4.74) hours.7

Clearance

The clearance rate was 124 ± 11 mL/hour/kg following intravenous administration.6

Adverse Effects
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Toxicity

The oral LD50 of viloxazine was 2000 mg/kg in rats.8

There is limited clinical experience with viloxazine overdose. According to case reports in the literature and postmarketing reports, doses ranging from 1000 mg to 6500 mg, which are 1.7 to 10.8 times the maximum recommended daily dose, resulted in overdose with drowsiness as the most reported symptom. Impaired consciousness, diminished reflexes, and increased heart rate have also been reported. There is no specific antidote for viloxazine overdose.7

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.
DrugInteraction
1,2-BenzodiazepineThe metabolism of 1,2-Benzodiazepine can be decreased when combined with Viloxazine.
AbacavirAbacavir may decrease the excretion rate of Viloxazine which could result in a higher serum level.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Viloxazine.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Viloxazine.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Viloxazine.
AcebutololThe metabolism of Acebutolol can be decreased when combined with Viloxazine.
AceclofenacAceclofenac may decrease the excretion rate of Viloxazine which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Viloxazine which could result in a higher serum level.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Viloxazine.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Viloxazine.
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Food Interactions
  • Take with or without food. A high-fat meal decreases drug Cmax and AUC and delays Tmax, but not to a clinically significant extent.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Viloxazine hydrochlorideOQW30I133235604-67-2HJOCKFVCMLCPTP-UHFFFAOYSA-N
International/Other Brands
Emovit
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
QelbreeCapsule, extended release150 mg/1OralSupernus Pharmaceuticals, Inc2021-04-02Not applicableUS flag
QelbreeCapsule, extended release100 mg/1OralSupernus Pharmaceuticals, Inc2021-04-02Not applicableUS flag
QelbreeCapsule, extended release200 mg/1OralSupernus Pharmaceuticals, Inc2021-04-02Not applicableUS flag

Categories

ATC Codes
N06AX09 — Viloxazine
Drug Categories
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 / Alkyl aryl ethers / Morpholines / Oxacyclic compounds / Dialkylamines / Dialkyl ethers / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Alkyl aryl ether / Amine / Aromatic heteromonocyclic compound / Azacycle / Dialkyl ether / Ether / Hydrocarbon derivative / Monocyclic benzene moiety / Morpholine / Organic nitrogen compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
5I5Y2789ZF
CAS number
46817-91-8
InChI Key
YWPHCCPCQOJSGZ-UHFFFAOYSA-N
InChI
InChI=1S/C13H19NO3/c1-2-15-12-5-3-4-6-13(12)17-10-11-9-14-7-8-16-11/h3-6,11,14H,2,7-10H2,1H3
IUPAC Name
2-[(2-ethoxyphenoxy)methyl]morpholine
SMILES
CCOC1=CC=CC=C1OCC1CNCCO1

References

General References
  1. Pinder RM, Brogden RN, Speight TM, Avery GS: Viloxazine: a review of its pharmacological properties and therapeutic efficacy in depressive illness. Drugs. 1977 Jun;13(6):401-21. [Article]
  2. Kergueris MF, Bourin M, Ribeyrol M, Beneroso N, Normand YL, Larousse C: Comparative pharmacokinetic study of conventional and sustained-release viloxazine in normal volunteers. Neuropsychobiology. 1989;20(3):136-40. [Article]
  3. Yu C: Metabolism and in vitro drug-drug interaction assessment of viloxazine. Xenobiotica. 2020 Nov;50(11):1285-1300. doi: 10.1080/00498254.2020.1767319. Epub 2020 Jun 10. [Article]
  4. Edinoff AN, Akuly HA, Wagner JH, Boudreaux MA, Kaplan LA, Yusuf S, Neuchat EE, Cornett EM, Boyer AG, Kaye AM, Kaye AD: Viloxazine in the Treatment of Attention Deficit Hyperactivity Disorder. Front Psychiatry. 2021 Dec 17;12:789982. doi: 10.3389/fpsyt.2021.789982. eCollection 2021. [Article]
  5. Yu C, Garcia-Olivares J, Candler S, Schwabe S, Maletic V: New Insights into the Mechanism of Action of Viloxazine: Serotonin and Norepinephrine Modulating Properties. J Exp Pharmacol. 2020 Aug 25;12:285-300. doi: 10.2147/JEP.S256586. eCollection 2020. [Article]
  6. Findling RL, Candler SA, Nasser AF, Schwabe S, Yu C, Garcia-Olivares J, O'Neal W, Newcorn JH: Viloxazine in the Management of CNS Disorders: A Historical Overview and Current Status. CNS Drugs. 2021 Jun;35(6):643-653. doi: 10.1007/s40263-021-00825-w. Epub 2021 May 18. [Article]
  7. FDA Approved Drug Products: QELBREE (viloxazine extended-release capsules), for oral use [Link]
  8. CymitQuimica: Viloxazine Hydrochloride MSDS [Link]
KEGG Drug
D08673
PubChem Compound
5666
PubChem Substance
310265093
ChemSpider
5464
BindingDB
50025691
RxNav
11196
ChEBI
94405
ChEMBL
CHEMBL306700
Wikipedia
Viloxazine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentAttention Deficit Hyperactivity Disorder (ADHD)1
1, 2CompletedOtherAttention Deficit Hyperactivity Disorder (ADHD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Capsule, extended releaseOral100 mg/1
Capsule, extended releaseOral150 mg/1
Capsule, extended releaseOral200 mg/1
Tablet
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US9603853No2017-03-282033-02-07US flag
US9358204No2016-06-072033-02-07US flag
US9662338No2017-05-302033-02-07US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)178-180https://www.trc-canada.com/prod-img/MSDS/V312440MSDS.pdf
Predicted Properties
PropertyValueSource
Water Solubility1.24 mg/mLALOGPS
logP1.71ALOGPS
logP1.49ChemAxon
logS-2.3ALOGPS
pKa (Strongest Basic)8.19ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area39.72 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity65.2 m3·mol-1ChemAxon
Polarizability26.32 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
Viloxazine binds to the norepinephrine transporter (NET, Ki= 0.63 µM) and inhibits the reuptake of norepinephrine (IC50=0.2 µM).
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
  1. Zheng G, Xue W, Wang P, Yang F, Li B, Li X, Li Y, Yao X, Zhu F: Exploring the Inhibitory Mechanism of Approved Selective Norepinephrine Reuptake Inhibitors and Reboxetine Enantiomers by Molecular Dynamics Study. Sci Rep. 2016 May 27;6:26883. doi: 10.1038/srep26883. [Article]
  2. Yu C, Garcia-Olivares J, Candler S, Schwabe S, Maletic V: New Insights into the Mechanism of Action of Viloxazine: Serotonin and Norepinephrine Modulating Properties. J Exp Pharmacol. 2020 Aug 25;12:285-300. doi: 10.2147/JEP.S256586. eCollection 2020. [Article]
  3. FDA Approved Drug Products: QELBREE (viloxazine extended-release capsules), for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding causes a conformation...
Gene Name
HTR2B
Uniprot ID
P41595
Uniprot Name
5-hydroxytryptamine receptor 2B
Molecular Weight
54297.41 Da
References
  1. Yu C, Garcia-Olivares J, Candler S, Schwabe S, Maletic V: New Insights into the Mechanism of Action of Viloxazine: Serotonin and Norepinephrine Modulating Properties. J Exp Pharmacol. 2020 Aug 25;12:285-300. doi: 10.2147/JEP.S256586. eCollection 2020. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
Gene Name
HTR2C
Uniprot ID
P28335
Uniprot Name
5-hydroxytryptamine receptor 2C
Molecular Weight
51820.705 Da
References
  1. Yu C, Garcia-Olivares J, Candler S, Schwabe S, Maletic V: New Insights into the Mechanism of Action of Viloxazine: Serotonin and Norepinephrine Modulating Properties. J Exp Pharmacol. 2020 Aug 25;12:285-300. doi: 10.2147/JEP.S256586. eCollection 2020. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
Viloxazine acts as a weak antagonist.
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. Findling RL, Candler SA, Nasser AF, Schwabe S, Yu C, Garcia-Olivares J, O'Neal W, Newcorn JH: Viloxazine in the Management of CNS Disorders: A Historical Overview and Current Status. CNS Drugs. 2021 Jun;35(6):643-653. doi: 10.1007/s40263-021-00825-w. Epub 2021 May 18. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
Viloxazine acts as a weak antagonist.
General Function
Protein homodimerization activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately ...
Gene Name
ADRB2
Uniprot ID
P07550
Uniprot Name
Beta-2 adrenergic receptor
Molecular Weight
46458.32 Da
References
  1. Findling RL, Candler SA, Nasser AF, Schwabe S, Yu C, Garcia-Olivares J, O'Neal W, Newcorn JH: Viloxazine in the Management of CNS Disorders: A Historical Overview and Current Status. CNS Drugs. 2021 Jun;35(6):643-653. doi: 10.1007/s40263-021-00825-w. Epub 2021 May 18. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
Viloxazine demonstrated weak competitive inhibition (< 25%).
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Findling RL, Candler SA, Nasser AF, Schwabe S, Yu C, Garcia-Olivares J, O'Neal W, Newcorn JH: Viloxazine in the Management of CNS Disorders: A Historical Overview and Current Status. CNS Drugs. 2021 Jun;35(6):643-653. doi: 10.1007/s40263-021-00825-w. Epub 2021 May 18. [Article]
  2. Yu C, Garcia-Olivares J, Candler S, Schwabe S, Maletic V: New Insights into the Mechanism of Action of Viloxazine: Serotonin and Norepinephrine Modulating Properties. J Exp Pharmacol. 2020 Aug 25;12:285-300. doi: 10.2147/JEP.S256586. eCollection 2020. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
Viloxazine demonstrated weak competitive inhibition (< 25%).
General Function
Histamine receptor activity
Specific Function
The H2 subclass of histamine receptors mediates gastric acid secretion. Also appears to regulate gastrointestinal motility and intestinal secretion. Possible role in regulating cell growth and diff...
Gene Name
HRH2
Uniprot ID
P25021
Uniprot Name
Histamine H2 receptor
Molecular Weight
40097.65 Da
References
  1. Findling RL, Candler SA, Nasser AF, Schwabe S, Yu C, Garcia-Olivares J, O'Neal W, Newcorn JH: Viloxazine in the Management of CNS Disorders: A Historical Overview and Current Status. CNS Drugs. 2021 Jun;35(6):643-653. doi: 10.1007/s40263-021-00825-w. Epub 2021 May 18. [Article]
  2. Yu C, Garcia-Olivares J, Candler S, Schwabe S, Maletic V: New Insights into the Mechanism of Action of Viloxazine: Serotonin and Norepinephrine Modulating Properties. J Exp Pharmacol. 2020 Aug 25;12:285-300. doi: 10.2147/JEP.S256586. eCollection 2020. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
Viloxazine demonstrated weak competitive inhibition (< 25%).
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. Findling RL, Candler SA, Nasser AF, Schwabe S, Yu C, Garcia-Olivares J, O'Neal W, Newcorn JH: Viloxazine in the Management of CNS Disorders: A Historical Overview and Current Status. CNS Drugs. 2021 Jun;35(6):643-653. doi: 10.1007/s40263-021-00825-w. Epub 2021 May 18. [Article]
  2. Yu C, Garcia-Olivares J, Candler S, Schwabe S, Maletic V: New Insights into the Mechanism of Action of Viloxazine: Serotonin and Norepinephrine Modulating Properties. J Exp Pharmacol. 2020 Aug 25;12:285-300. doi: 10.2147/JEP.S256586. eCollection 2020. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
Viloxazine demonstrated weak competitive inhibition (< 25%).
General Function
G-protein coupled acetylcholine receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM2
Uniprot ID
P08172
Uniprot Name
Muscarinic acetylcholine receptor M2
Molecular Weight
51714.605 Da
References
  1. Findling RL, Candler SA, Nasser AF, Schwabe S, Yu C, Garcia-Olivares J, O'Neal W, Newcorn JH: Viloxazine in the Management of CNS Disorders: A Historical Overview and Current Status. CNS Drugs. 2021 Jun;35(6):643-653. doi: 10.1007/s40263-021-00825-w. Epub 2021 May 18. [Article]
  2. Yu C, Garcia-Olivares J, Candler S, Schwabe S, Maletic V: New Insights into the Mechanism of Action of Viloxazine: Serotonin and Norepinephrine Modulating Properties. J Exp Pharmacol. 2020 Aug 25;12:285-300. doi: 10.2147/JEP.S256586. eCollection 2020. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
Viloxazine demonstrated weak competitive inhibition (< 25%).
General Function
Receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM3
Uniprot ID
P20309
Uniprot Name
Muscarinic acetylcholine receptor M3
Molecular Weight
66127.445 Da
References
  1. Findling RL, Candler SA, Nasser AF, Schwabe S, Yu C, Garcia-Olivares J, O'Neal W, Newcorn JH: Viloxazine in the Management of CNS Disorders: A Historical Overview and Current Status. CNS Drugs. 2021 Jun;35(6):643-653. doi: 10.1007/s40263-021-00825-w. Epub 2021 May 18. [Article]
  2. Yu C, Garcia-Olivares J, Candler S, Schwabe S, Maletic V: New Insights into the Mechanism of Action of Viloxazine: Serotonin and Norepinephrine Modulating Properties. J Exp Pharmacol. 2020 Aug 25;12:285-300. doi: 10.2147/JEP.S256586. eCollection 2020. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
Viloxazine demonstrated weak competitive inhibition (< 25%).
General Function
Guanyl-nucleotide exchange factor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM4
Uniprot ID
P08173
Uniprot Name
Muscarinic acetylcholine receptor M4
Molecular Weight
53048.65 Da
References
  1. Findling RL, Candler SA, Nasser AF, Schwabe S, Yu C, Garcia-Olivares J, O'Neal W, Newcorn JH: Viloxazine in the Management of CNS Disorders: A Historical Overview and Current Status. CNS Drugs. 2021 Jun;35(6):643-653. doi: 10.1007/s40263-021-00825-w. Epub 2021 May 18. [Article]
  2. Yu C, Garcia-Olivares J, Candler S, Schwabe S, Maletic V: New Insights into the Mechanism of Action of Viloxazine: Serotonin and Norepinephrine Modulating Properties. J Exp Pharmacol. 2020 Aug 25;12:285-300. doi: 10.2147/JEP.S256586. eCollection 2020. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
In rats, viloxazine was a very weak, competitive, and reversible inhibitor.
General Function
Serotonin binding
Specific Function
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
Gene Name
MAOA
Uniprot ID
P21397
Uniprot Name
Amine oxidase [flavin-containing] A
Molecular Weight
59681.27 Da
References
  1. Martinez C, Dominiak P, Kees F, Grobecker H: Inhibition of monoamine oxidase by viloxazine in rats. Arzneimittelforschung. 1986 May;36(5):800-3. [Article]
  2. Findling RL, Candler SA, Nasser AF, Schwabe S, Yu C, Garcia-Olivares J, O'Neal W, Newcorn JH: Viloxazine in the Management of CNS Disorders: A Historical Overview and Current Status. CNS Drugs. 2021 Jun;35(6):643-653. doi: 10.1007/s40263-021-00825-w. Epub 2021 May 18. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
In rats, viloxazine was a very weak, competitive, and reversible inhibitor.
General Function
Primary amine oxidase activity
Specific Function
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
Gene Name
MAOB
Uniprot ID
P27338
Uniprot Name
Amine oxidase [flavin-containing] B
Molecular Weight
58762.475 Da
References
  1. Martinez C, Dominiak P, Kees F, Grobecker H: Inhibition of monoamine oxidase by viloxazine in rats. Arzneimittelforschung. 1986 May;36(5):800-3. [Article]
  2. Findling RL, Candler SA, Nasser AF, Schwabe S, Yu C, Garcia-Olivares J, O'Neal W, Newcorn JH: Viloxazine in the Management of CNS Disorders: A Historical Overview and Current Status. CNS Drugs. 2021 Jun;35(6):643-653. doi: 10.1007/s40263-021-00825-w. Epub 2021 May 18. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
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
  1. Yu C: Metabolism and in vitro drug-drug interaction assessment of viloxazine. Xenobiotica. 2020 Nov;50(11):1285-1300. doi: 10.1080/00498254.2020.1767319. Epub 2020 Jun 10. [Article]
  2. FDA Approved Drug Products: QELBREE (viloxazine extended-release capsules), for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da
References
  1. FDA Approved Drug Products: QELBREE (viloxazine extended-release capsules), for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme displays activity toward several classes of xeno...
Gene Name
UGT2B15
Uniprot ID
P54855
Uniprot Name
UDP-glucuronosyltransferase 2B15
Molecular Weight
61035.815 Da
References
  1. FDA Approved Drug Products: QELBREE (viloxazine extended-release capsules), for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
Viloxazine is a reversible inhibitor of this enzyme.
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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 oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Yu C: Metabolism and in vitro drug-drug interaction assessment of viloxazine. Xenobiotica. 2020 Nov;50(11):1285-1300. doi: 10.1080/00498254.2020.1767319. Epub 2020 Jun 10. [Article]
  2. Griffin J. and D'Arcy P. (1997). A manual of adverse drug interactions (5th ed.). Elsevier. [ISBN:0-444-82406-5]
  3. FDA Approved Drug Products: QELBREE (viloxazine extended-release capsules), for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
Viloxazine is a reversible inhibitor of this enzyme.
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. FDA Approved Drug Products: QELBREE (viloxazine extended-release capsules), for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
Viloxazine is a reversible inhibitor of this enzyme.
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
  1. FDA Approved Drug Products: QELBREE (viloxazine extended-release capsules), for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
Viloxazine is a reversible inhibitor of this enzyme.
General Function
Oxygen binding
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 oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. FDA Approved Drug Products: QELBREE (viloxazine extended-release capsules), for oral use [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Monovalent cation:proton antiporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. FDA Approved Drug Products: QELBREE (viloxazine extended-release capsules), for oral use [Link]

Drug created at October 16, 2015 19:16 / Updated at May 07, 2022 17:11