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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- Approved, Investigational, Withdrawn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
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Attention deficit hyperactivity disorder (adhd) •••••••••••• ••••••••••• •••••• ••••••••• •••••••• •••••••• ••••••• - Contraindications & Blackbox Warnings
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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
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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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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. - 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
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data4 Recruiting Treatment Attention Deficit Hyperactivity Disorder (ADHD) 1 somestatus stop reason just information to hide 3 Active Not Recruiting Treatment Attention Deficit Hyperactivity Disorder (ADHD) 1 somestatus stop reason just information to hide 3 Completed Treatment Attention Deficit Hyperactivity Disorder (ADHD) 2 somestatus stop reason just information to hide 1, 2 Completed Other Attention Deficit Hyperactivity Disorder (ADHD) 1 somestatus stop reason just information to hide
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 US11458143 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 splash10-052o-9630000000-de4a4c4b2490bdfb2e62 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-000i-0490000000-25cda4161fc540bb62e1 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-014r-4920000000-67fe267fbf476f89a1a5 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0udi-5910000000-f2d296f7605585d4cf5d Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4i-3900000000-f052261682447555ffd1 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0udi-7900000000-ebdcae3ceb3ed754b86b Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-052f-9600000000-65691fc7fb6d36e74c0d Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 148.58481 predictedDeepCCS 1.0 (2019) [M+H]+ 151.17882 predictedDeepCCS 1.0 (2019) [M+Na]+ 159.09804 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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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
- Mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline) (PubMed:2008212, PubMed:8125921). Can also mediate sodium- and chloride-dependent transport of dopamine (PubMed:11093780, PubMed:8125921)
- Specific Function
- Actin binding
- 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
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:18703043, PubMed:23519210, PubMed:7926008, PubMed:8078486, PubMed:8143856, PubMed:8882600). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances (PubMed:12970106, PubMed:18703043, PubMed:23519210, PubMed:23519215, PubMed:24357322, PubMed:28129538, PubMed:7926008, PubMed:8078486, PubMed:8143856). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors (PubMed:23519215, PubMed:28129538, PubMed:8078486, PubMed:8143856, PubMed:8882600). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:23519215, PubMed:28129538). Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores (PubMed:18703043, PubMed:23519215, PubMed:28129538, PubMed:8078486, PubMed:8143856, PubMed:8882600). Plays a role in the regulation of dopamine and 5-hydroxytryptamine release, 5-hydroxytryptamine uptake and in the regulation of extracellular dopamine and 5-hydroxytryptamine levels, and thereby affects neural activity. May play a role in the perception of pain (By similarity). Plays a role in the regulation of behavior, including impulsive behavior (PubMed:21179162). Required for normal proliferation of embryonic cardiac myocytes and normal heart development. Protects cardiomyocytes against apoptosis. Plays a role in the adaptation of pulmonary arteries to chronic hypoxia. Plays a role in vasoconstriction. Required for normal osteoblast function and proliferation, and for maintaining normal bone density. Required for normal proliferation of the interstitial cells of Cajal in the intestine (By similarity)
- Specific Function
- G protein-coupled serotonin receptor activity
- 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]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General 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-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis
- Specific Function
- 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding
- Gene Name
- HTR2C
- Uniprot ID
- P28335
- Uniprot Name
- 5-hydroxytryptamine receptor 2C
- Molecular Weight
- 51804.645 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
- 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) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes
- Specific Function
- Alpha1-adrenergic receptor activity
- 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
- 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 30-fold greater affinity than it does norepinephrine
- Specific Function
- Adenylate cyclase binding
- 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
- 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 catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system
- Specific Function
- G protein-coupled serotonin receptor activity
- 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
- 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 differentiation. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and, through a separate G protein-dependent mechanism, the phosphoinositide/protein kinase (PKC) signaling pathway (By similarity)
- Specific Function
- G protein-coupled serotonin receptor activity
- 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
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover
- Specific Function
- G protein-coupled acetylcholine receptor activity
- 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
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol
- Specific Function
- Arrestin family protein binding
- 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
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover
- Specific Function
- Acetylcholine binding
- 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
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase
- Specific Function
- G protein-coupled acetylcholine receptor activity
- 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
- Catalyzes the oxidative deamination of primary and some secondary amine such as neurotransmitters, with concomitant reduction of oxygen to hydrogen peroxide and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:18391214, PubMed:20493079, PubMed:24169519, PubMed:8316221). Preferentially oxidizes serotonin (PubMed:20493079, PubMed:24169519). Also catalyzes the oxidative deamination of kynuramine to 3-(2-aminophenyl)-3-oxopropanal that can spontaneously condense to 4-hydroxyquinoline (By similarity)
- Specific Function
- Aliphatic amine oxidase activity
- 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
- Catalyzes the oxidative deamination of primary and some secondary amines such as neurotransmitters, and exogenous amines including the tertiary amine, neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), with concomitant reduction of oxygen to hydrogen peroxide and participates in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:11049757, PubMed:11134050, PubMed:20493079, PubMed:8316221, PubMed:8665924). Preferentially degrades benzylamine and phenylethylamine (PubMed:11049757, PubMed:11134050, PubMed:20493079, PubMed:8316221, PubMed:8665924)
- Specific Function
- Aliphatic amine oxidase activity
- 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
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
- Specific Function
- Anandamide 11,12 epoxidase activity
- 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
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15470161, PubMed:15472229, PubMed:18004212, PubMed:18052087, PubMed:18674515, PubMed:19545173). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol and estrone (PubMed:15472229). Also catalyzes the glucuronidation of the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist caderastan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:20610558). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161, PubMed:18004212)
- Specific Function
- Enzyme binding
- Gene Name
- UGT1A9
- Uniprot ID
- O60656
- Uniprot Name
- UDP-glucuronosyltransferase 1A9
- 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
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:16595710, PubMed:18719240, PubMed:23288867, PubMed:7835232, PubMed:9295060). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:7835232). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (testosterone, androsterone) and estrogens (estradiol, epiestradiol, estriol, catechol estrogens) (PubMed:16595710, PubMed:18719240, PubMed:23288867, PubMed:7835232, PubMed:9295060). Displays glucuronidation activity toward several classes of xenobiotic substrates, including phenolic compounds (eugenol, 4-nitrophenol, 4-hydroxybiphenyl) and phenylpropanoids (naringenin, coumarins) (PubMed:7835232). Catalyzes the glucuronidation of monoterpenoid alcohols such as borneol, menthol and isomenthol, a class of natural compounds used in essential oils (By similarity)
- Specific Function
- Glucuronosyltransferase activity
- 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
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
- Specific Function
- Aromatase activity
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58406.915 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
- A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids (PubMed:12865317, PubMed:21289075). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:21289075). Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2 (PubMed:12865317, PubMed:21289075). Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs (PubMed:11695850, PubMed:22909231). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850)
- Specific Function
- Anandamide 11,12 epoxidase activity
- 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
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- 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
- A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
- Specific Function
- Aromatase activity
- 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
- Multidrug efflux pump that functions as a H(+)/organic cation antiporter (PubMed:16330770, PubMed:17509534). Plays a physiological role in the excretion of cationic compounds including endogenous metabolites, drugs, toxins through the kidney and liver, into urine and bile respectively (PubMed:16330770, PubMed:17495125, PubMed:17509534, PubMed:17582384, PubMed:18305230, PubMed:19158817, PubMed:21128598, PubMed:24961373). Mediates the efflux of endogenous compounds such as creatinine, vitamin B1/thiamine, agmatine and estrone-3-sulfate (PubMed:16330770, PubMed:17495125, PubMed:17509534, PubMed:17582384, PubMed:18305230, PubMed:19158817, PubMed:21128598, PubMed:24961373). May also contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable)
- Specific Function
- Antiporter activity
- 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 June 02, 2024 21:54