Viloxazine
Identification
- Generic Name
- Viloxazine
- DrugBank Accession Number
- DB09185
- Background
Viloxazine is a selective norepinephrine reuptake inhibitor (NRI) that was used in some European countries as an antidepressant drug. It structurally differs from conventional tri- or tetra-cyclic antidepressants and it does not produce sedative anticholinergic or adrenergic effects in man 1. While displaying amphetamine-like CNS stimulant effects, there is little evidence of drug dependence from viloxazine therapy. Viloxazine hydrochloride is a common active ingredient in drug formulation. It was discovered and brought to market in 1976 by Imperial Chemical Industries and in early 2000's, it was withdrawn from the market.
- 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- Approved, Investigational, Withdrawn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
Indicated for the treatment of clinical depression.
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Contraindications & Blackbox WarningsWith our commercial data, access important information on dangerous risks, contraindications, and adverse effects.Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects- Pharmacodynamics
Viloxazine is a selective noradrenaline reuptake inhibitor (NRI) with minimal inhibitory effect on the reuptake of 5-HT. It is also shown to upregulate the levels of GABA-B receptors in the rat frontal cortex. It is shown to form a complex with the human norepinephrine transporter (hNET) 8. The S(-)-stereoisomer of viloxazine exhibits more potent pharmacological actions 9.
- Mechanism of action
Viloxazine inhibits noradrenaline uptake in rat and mouse heart tissue and has a weak effect on the uptake of 5-HT 1. In a docking study, the amino group of viloxazine points towards Asp75 in the drug binding pocket of the transporter and forms hydrogen bonds with Phe72, Asp75 and Phe317. The rest of the drug molecule forms hydrophobic interactions with other key residues in the binding pocket 8.
Target Actions Organism ASodium-dependent noradrenaline transporter inhibitorHumans - Absorption
Viloxazine is rapidly and almost completely absorbed following oral administration. The peak plasma concentration (Cmax) ranges between 540 and 1,600 ng/mL and the mean time to reach Cmax is approximately 86 minutes 6. Increase in plasma drug concentration is dose-proportional 1.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Viloxazine is thought to be extensively metabolized into 5-hydroxy derivative and glucuronidated phenol. Other detected metabolites include 4-hydroxy isomer and its glucuronide, together with the sulphate conjugates of the phenolic metabolites 1.
- Route of elimination
Viloxazine is rapidly eliminated via urine and about 2% of the administered dose is recovered in the feces. About 12-15% of the total drug is eliminated as unchanged parent drug 1.
- Half-life
Elimination half life is approximately 3-4 hours 6.
- Clearance
Not Available
- Adverse Effects
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Common adverse effects are nausea and vomiting. Other side effects are dry mouth, dizziness, headache, drowsiness, sleep disturbances, bad taste, anorexia, heartburn and indigestion, constipation, diarrhoea, ataxia, tremor, dyskinesia, paraesthesia, confusion, restlessness, irritability, hypomania and mania, sweating, palpitation, tachycardia, increased and decreased blood pressure, pruritus and skin rashes 6.
- 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 risk or severity of adverse effects can be increased when Viloxazine is combined with 1,2-Benzodiazepine. Abacavir Abacavir may decrease the excretion rate of Viloxazine which could result in a higher serum level. 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 Acetaminophen may decrease the excretion rate of Viloxazine which could result in a higher serum level. Acetazolamide The risk or severity of adverse effects can be increased when Acetazolamide is combined with Viloxazine. Acetophenazine The risk or severity of adverse effects can be increased when Acetophenazine is combined with Viloxazine. Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Viloxazine which could result in a higher serum level. Aclidinium Aclidinium may increase the central nervous system depressant (CNS depressant) activities of Viloxazine. 
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- Not Available
Products
Comprehensive & structured drug product infoFrom application numbers to product codes, connect different identifiers through our commercial datasets.Easily connect various identifiers back to our datasets- 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 Uptake Inhibitors
- Antidepressive Agents
- Antidepressive Agents, Second-Generation
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (weak)
- Cytochrome P-450 Enzyme Inhibitors
- Drugs that are Mainly Renally Excreted
- Membrane Transport Modulators
- Morpholines
- Nervous System
- Neurotransmitter Agents
- Neurotransmitter Uptake Inhibitors
- Oxazines
- 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 / 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. [PubMed:324751]
- Lippman W, Pugsley TA: Effects of viloxazine, an antidepressant agent, on biogenic amine uptake mechanisms and related activities. Can J Physiol Pharmacol. 1976 Aug;54(4):494-509. [PubMed:974878]
- Sebjanic V, Grombein S: Viloxazine (Vivalan ICI) in depression: results of a field trial of 276 patients in neuropsychiatric practice. Adv Biochem Psychopharmacol. 1982;32:113-20. [PubMed:7046360]
- Case DE, Reeves PR: The disposition and metabolism of I.C.I. 58,834 (viloxazine) in humans. Xenobiotica. 1975 Feb;5(2):113-29. [PubMed:1154799]
- Thomare P, Bourin M, Kergueris MF, Ortega A, Larousse C: Effects of administration route on pharmacokinetics of viloxazine in the rabbit. Methods Find Exp Clin Pharmacol. 1992 Mar;14(2):125-9. [PubMed:1598024]
- 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. [PubMed:2761683]
- Vandel B, Vandel S, Jounet JM, Blum D: Pharmacokinetics of viloxazine hydrochloride in man. Eur J Drug Metab Pharmacokinet. 1982 Jan-Mar;7(1):65-8. [PubMed:7067726]
- 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. [PubMed:27230580]
- Danchev ND, Rozhanets VV, Zhmurenko LA, Glozman OM, Zagorevskii VA: [Behavioral and radioreceptor analysis of viloxazine stereoisomers]. Biull Eksp Biol Med. 1984 May;97(5):576-8. [PubMed:6326891]
- 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 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
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- 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
- 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
- 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. [PubMed:27230580]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- 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
- Griffin J. and D'Arcy P. (1997). A manual of adverse drug interactions (5th ed.). Elsevier. [ISBN:0-444-82406-5]
Drug created on October 16, 2015 19:16 / Updated on April 16, 2021 09:37