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- Approved, Investigational, Withdrawn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
Structure for Viloxazine (DB09185)
- 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
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- 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
Target Actions Organism ASodium-dependent noradrenaline transporter inhibitorHumans A5-hydroxytryptamine receptor 2B antagonistHumans A5-hydroxytryptamine receptor 2C agonistHumans UAlpha-1B adrenergic receptor antagonistHumans UBeta-2 adrenergic receptor antagonistHumans UHistamine H1 receptor antagonistHumans UHistamine H2 receptor antagonistHumans UMuscarinic acetylcholine receptor M1 antagonistHumans UMuscarinic acetylcholine receptor M2 antagonistHumans UMuscarinic acetylcholine receptor M3 antagonistHumans UMuscarinic acetylcholine receptor M4 antagonistHumans UAmine oxidase [flavin-containing] A inhibitorHumans UAmine oxidase [flavin-containing] B inhibitorHumans - 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
Hover over products below to view reaction partners
- 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
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- 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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The metabolism of 1,2-Benzodiazepine can be decreased when combined with Viloxazine. Abacavir Abacavir may decrease the excretion rate of Viloxazine which could result in a higher serum level. Abemaciclib The metabolism of Abemaciclib can be decreased when combined with Viloxazine. Abiraterone The metabolism of Abiraterone can be decreased when combined with Viloxazine. Acalabrutinib The metabolism of Acalabrutinib can be decreased when combined with Viloxazine. Acebutolol The metabolism of Acebutolol can be decreased when combined with Viloxazine. Aceclofenac Aceclofenac may decrease the excretion rate of Viloxazine which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Viloxazine which could result in a higher serum level. Acenocoumarol The metabolism of Acenocoumarol can be decreased when combined with Viloxazine. Acetaminophen The metabolism of Acetaminophen can be decreased when combined with Viloxazine. 
Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - 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
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Viloxazine hydrochloride OQW30I1332 35604-67-2 HJOCKFVCMLCPTP-UHFFFAOYSA-N - International/Other Brands
- Emovit
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Qelbree Capsule, extended release 150 mg/1 Oral Supernus Pharmaceuticals, Inc 2021-04-02 Not applicable US 
Qelbree Capsule, extended release 100 mg/1 Oral Supernus Pharmaceuticals, Inc 2021-04-02 Not applicable US Qelbree Capsule, extended release 200 mg/1 Oral Supernus Pharmaceuticals, Inc 2021-04-02 Not applicable US
Categories
- ATC Codes
- N06AX09 — Viloxazine
- Drug Categories
- Adrenergic Agents
- Adrenergic alpha-1 Receptor Antagonists
- Adrenergic alpha-Antagonists
- Adrenergic Antagonists
- Adrenergic beta-Antagonists
- Adrenergic Uptake Inhibitors
- Anticholinergic Agents
- Antidepressive Agents
- Antidepressive Agents, Second-Generation
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (strong)
- Cytochrome P-450 CYP1A2 Inhibitors (weak)
- Cytochrome P-450 CYP2B6 Inhibitors
- Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A5 Inhibitors
- Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- Histamine Antagonists
- Histamine H1 Antagonists
- Histamine H2 Antagonists
- Histamine H3 Antagonists
- MATE 1 Inhibitors
- MATE inhibitors
- Membrane Transport Modulators
- Monoamine Oxidase A Inhibitors
- Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates
- Monoamine Oxidase B Inhibitors
- Monoamine Oxidase Inhibitors
- Morpholines
- Muscarinic Antagonists
- Nervous System
- Neurotransmitter Agents
- Neurotransmitter Uptake Inhibitors
- Norepinephrine Reuptake Inhibitor
- Norepinephrine Uptake Inhibitors
- Oxazines
- Psychoanaleptics
- Psychotropic Drugs
- UGT1A9 Substrates
- 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
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- FDA Approved Drug Products: QELBREE (viloxazine extended-release capsules), for oral use [Link]
- CymitQuimica: Viloxazine Hydrochloride MSDS [Link]
- External Links
- KEGG Drug
- D08673
- PubChem Compound
- 5666
- PubChem Substance
- 310265093
- ChemSpider
- 5464
- BindingDB
- 50025691
- 11196
- ChEBI
- 94405
- ChEMBL
- CHEMBL306700
- Wikipedia
- Viloxazine
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Attention Deficit Hyperactivity Disorder (ADHD) 1 3 Completed Treatment Attention Deficit Hyperactivity Disorder (ADHD) 1 1, 2 Completed Other Attention Deficit Hyperactivity Disorder (ADHD) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule, extended release Oral 100 mg/1 Capsule, extended release Oral 150 mg/1 Capsule, extended release Oral 200 mg/1 Tablet - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9603853 No 2017-03-28 2033-02-07 US US9358204 No 2016-06-07 2033-02-07 US US9662338 No 2017-05-30 2033-02-07 US US11324753 No 2009-09-04 2029-09-04 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 178-180 https://www.trc-canada.com/prod-img/MSDS/V312440MSDS.pdf - Predicted Properties
Property Value Source Water Solubility 1.24 mg/mL ALOGPS logP 1.71 ALOGPS logP 1.49 ChemAxon logS -2.3 ALOGPS pKa (Strongest Basic) 8.19 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 5 ChemAxon Refractivity 65.2 m3·mol-1 ChemAxon Polarizability 26.32 Å3 ChemAxon Number of Rings 2 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule Yes ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available 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
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- 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
- 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]
- 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]
- 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
- 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
- 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
- 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
- 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
- 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]
- 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
- 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]
- 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
- 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]
- 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
- 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]
- 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
- 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]
- 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
- 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]
- 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
- Martinez C, Dominiak P, Kees F, Grobecker H: Inhibition of monoamine oxidase by viloxazine in rats. Arzneimittelforschung. 1986 May;36(5):800-3. [Article]
- 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
- Martinez C, Dominiak P, Kees F, Grobecker H: Inhibition of monoamine oxidase by viloxazine in rats. Arzneimittelforschung. 1986 May;36(5):800-3. [Article]
- 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
- SubstrateInhibitor
- 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
- 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
- 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
- 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
- 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]
- Griffin J. and D'Arcy P. (1997). A manual of adverse drug interactions (5th ed.). Elsevier. [ISBN:0-444-82406-5]
- 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
- 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
- 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
- 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
- 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