Mexiletine
Explore a selection of our essential drug information below, or:
Identification
- Summary
Mexiletine is a class 1B antiarrhythmic agent used in the treatment of documented ventricular arrhythmias that warrant treatment.
- Generic Name
- Mexiletine
- DrugBank Accession Number
- DB00379
- Background
Antiarrhythmic agent pharmacologically similar to lidocaine. It may have some anticonvulsant properties.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 179.2588
Monoisotopic: 179.131014171 - Chemical Formula
- C11H17NO
- Synonyms
- (±)-1-(2,6-dimethylphenoxy)propan-2-amine
- (2RS)-1-(2,6-dimethylphenoxy)-2-aminopropane
- 1-(2,6-dimethylphenoxy)-2-propanamine
- 1-(2',6'-dimethylphenoxy)-2-aminopropane
- 1-methyl-2-(2,6-xylyloxy)ethanamine
- Mexiletina
- Mexilétine
- Mexiletine
- Mexiletinum
- External IDs
- Kö 1173
Pharmacology
- Indication
For the treatment of ventricular tachycardia and symptomatic premature ventricular beats, and prevention of ventricular fibrillation.
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
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Ventricular arrhythmia •••••••••••• Management of Ventricular tachycardia, sustained •••••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Mexiletine is a local anesthetic, antiarrhythmic agent (Class Ib), structurally similar to lidocaine, but orally active. Mexiletine has fast onset and offset kinetics, meaning that they have little or no effect at slower heart rates, and more effects at faster heart rates. It shortens the action potential duration, reduces refractoriness, and decreases Vmax in partially depolarized cells with fast response action potentials. Mexiletine either does not change the action potential duration, or decreases the action potential duration.
- Mechanism of action
Mexiletine, like lidocaine, inhibits the inward sodium current required for the initiation and conduction of impulses, thus reducing the rate of rise of the action potential, Phase 0. It achieves this reduced sodium current by inhibiting sodium channels. Mexiletine decreases the effective refractory period (ERP) in Purkinje fibers in the heart. The decrease in ERP is of lesser magnitude than the decrease in action potential duration (APD), which results in an increase in the ERP/APD ratio. It does not significantly affect resting membrane potential or sinus node automaticity, left ventricular function, systolic arterial blood pressure, atrioventricular (AV) conduction velocity, or QRS or QT intervals
Target Actions Organism ASodium channel protein type 5 subunit alpha inhibitorHumans UAryl hydrocarbon receptor agonistHumans - Absorption
Well absorbed (bioavailability 90%) from the gastrointenstinal tract.
- Volume of distribution
- 5 to 7 L/lg
- Protein binding
50-60%
- Metabolism
Primarily hepatic (85%) via CYP2D6 and CYP1A2 (primarily CYP2D6).
Hover over products below to view reaction partners
- Route of elimination
Approximately 10% is excreted unchanged by the kidney. The urinary excretion of N-methylmexiletine in man is less than 0.5%.
- Half-life
10-12 hours
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Symptoms of overdose include nausea, hypotension, sinus bradycardia, paresthesia, seizures, bundle branch block, AV heart block, asystole, ventricular tachyarrythmia, including ventricular fibrillation, cardiovascular collapse, and coma.
- Pathways
Pathway Category Mexiletine Action Pathway Drug action - 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 softwareAbametapir The serum concentration of Mexiletine can be increased when it is combined with Abametapir. Abatacept The metabolism of Mexiletine can be increased when combined with Abatacept. Abiraterone The serum concentration of Mexiletine can be increased when it is combined with Abiraterone. Acebutolol Mexiletine may increase the arrhythmogenic activities of Acebutolol. Acenocoumarol The metabolism of Acenocoumarol can be decreased when combined with Mexiletine. - Food Interactions
- Take with food. Food reduces irritation.
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 Mexiletine hydrochloride 606D60IS38 5370-01-4 NFEIBWMZVIVJLQ-UHFFFAOYSA-N - Product Images
- International/Other Brands
- Cirumimeru (Tsuruhara Seiyaku) / Mekiratin (Ohara Yakuhin) / Melate (Medisa Shinyaku) / Meldest (Taiyo Pharmaceutical) / Meletin (Taiwan Biotech) / Mequitolide (Towa Yakuhin) / Metorekicin (Choseido Pharmaceutical) / Mexicord (Polfa Grodzisk) / Mexitilen (Boehringer Ingelheim) / Minsetil (Zdravlje) / Mobalen (Tatsumi Kagaku) / Mugadine (Yung Shin) / Olzoron (Kobayashi Kako) / Poeruten (Yoshindo) / Ritalmex (Valeant) / Toi (Kyorin Rimedio) / Tumetil (Boehringer Ingelheim)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Mexiletine HCl Capsule 150 mg/1 Oral Watson Pharmaceuticals 2008-04-29 Not applicable US Mexiletine HCl Capsule 250 mg/1 Oral Watson Pharmaceuticals 2008-04-29 Not applicable US Mexiletine HCl Capsule 200 mg/1 Oral Watson Pharmaceuticals 2008-04-29 Not applicable US Mexitil Capsule 150 mg/1 Oral Boehringer Ingelheim 1985-12-30 2005-01-04 US Mexitil Capsule 150 mg/1 Oral Physicians Total Care, Inc. 1985-12-30 2000-06-30 US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Alti-mexiletine Capsule 100 mg Oral Altimed Pharma Inc. 1997-11-07 2001-09-05 Canada Alti-mexiletine Capsule 200 mg / cap Oral Altimed Pharma Inc. 1997-11-07 2001-09-05 Canada Mexiletine Hydrochloride Capsule 250 mg/1 Oral Senores Pharmaceuticals, Inc. 2021-11-29 Not applicable US Mexiletine Hydrochloride Capsule 250 mg/1 Oral bryant ranch prepack 2020-06-22 Not applicable US Mexiletine Hydrochloride Capsule 150 mg/1 Oral Ingenus Pharmaceuticals, LLC 2021-01-26 Not applicable US
Categories
- ATC Codes
- C01BB02 — Mexiletine
- Drug Categories
- Amines
- Antiarrhythmic agents
- Antiarrhythmics, Class I
- Antiarrhythmics, Class Ib
- Benzene Derivatives
- Cardiac Therapy
- Cardiovascular Agents
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (moderate)
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP2E1 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Membrane Transport Modulators
- Phenols
- Phenyl Ethers
- Propylamines
- Sodium Channel Blockers
- Voltage-Gated Sodium Channel Blockers
- 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
- m-Xylenes / Phenoxy compounds / Alkyl aryl ethers / Organopnictogen compounds / Monoalkylamines / Hydrocarbon derivatives
- Substituents
- Alkyl aryl ether / Amine / Aromatic homomonocyclic compound / Ether / Hydrocarbon derivative / M-xylene / Monocyclic benzene moiety / Organic nitrogen compound / Organic oxygen compound / Organonitrogen compound
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- aromatic ether, primary amino compound (CHEBI:6916)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 1U511HHV4Z
- CAS number
- 31828-71-4
- InChI Key
- VLPIATFUUWWMKC-UHFFFAOYSA-N
- InChI
- InChI=1S/C11H17NO/c1-8-5-4-6-9(2)11(8)13-7-10(3)12/h4-6,10H,7,12H2,1-3H3
- IUPAC Name
- 1-(2,6-dimethylphenoxy)propan-2-amine
- SMILES
- CC(N)COC1=C(C)C=CC=C1C
References
- Synthesis Reference
Margarita Ortiz-Marciales, Kun Huang, Viatcheslav Stepanenko, Melvin De Jesus, Wildeliz Correa, "Method of synthesizing enantiopure mexiletine analogues and novel b-thiophenoxy and pyridyl ethers." U.S. Patent US08012901, issued September 06, 2011.
US08012901- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0014523
- KEGG Compound
- C07220
- PubChem Compound
- 4178
- PubChem Substance
- 46505491
- ChemSpider
- 4034
- BindingDB
- 50117271
- 6926
- ChEBI
- 6916
- ChEMBL
- CHEMBL558
- Therapeutic Targets Database
- DAP000505
- PharmGKB
- PA450488
- Guide to Pharmacology
- GtP Drug Page
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Mexiletine
- FDA label
- Download (1.21 MB)
- MSDS
- Download (47.1 KB)
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 dataNot Available Active Not Recruiting Not Available Steinert's Disease 1 somestatus stop reason just information to hide Not Available Active Not Recruiting Treatment Myotonic Disorders 1 somestatus stop reason just information to hide Not Available Recruiting Treatment Giant T-wave Electrical Alternans 1 somestatus stop reason just information to hide Not Available Recruiting Treatment Non-dystrophic Myotonias 1 somestatus stop reason just information to hide 4 Completed Treatment Cryptogenic Sensory Peripheral Neuropathy 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Sandoz inc
- Teva pharmaceuticals usa inc
- Watson laboratories inc
- Boehringer ingelheim
- Packagers
- Atlantic Biologicals Corporation
- Kaiser Foundation Hospital
- Murfreesboro Pharmaceutical Nursing Supply
- Novopharm Ltd.
- Nucare Pharmaceuticals Inc.
- Physicians Total Care Inc.
- Prescript Pharmaceuticals
- Roxane Labs
- Southwood Pharmaceuticals
- Teva Pharmaceutical Industries Ltd.
- Warrick Pharmaceuticals Corp.
- Dosage Forms
Form Route Strength Capsule Oral 100 mg Capsule Oral 200 mg / cap Capsule Oral 150 mg/1 Capsule Oral 200 mg/1 Capsule Oral 250 mg/1 Capsule Oral Injection, solution Capsule Oral 200 mg Capsule Oral 167 MG - Prices
Unit description Cost Unit Mexitil 250 mg capsule 1.85USD capsule Mexiletine HCl 250 mg capsule 1.6USD capsule Mexiletine 250 mg capsule 1.54USD capsule Mexiletine HCl 200 mg capsule 1.38USD capsule Mexiletine 200 mg capsule 1.33USD capsule Mexitil 200 mg capsule 1.23USD capsule Novo-Mexiletine 200 mg Capsule 1.19USD capsule Mexiletine HCl 150 mg capsule 1.16USD capsule Mexiletine 150 mg capsule 1.11USD capsule Novo-Mexiletine 100 mg Capsule 0.89USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 203-205 °C PhysProp water solubility 8.25 mg/mL Not Available logP 2.15 MANNHOLD,R ET AL. (1990) pKa 9.2 Not Available - Predicted Properties
Property Value Source Water Solubility 0.538 mg/mL ALOGPS logP 2.17 ALOGPS logP 2.46 Chemaxon logS -2.5 ALOGPS pKa (Strongest Basic) 9.52 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 35.25 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 54.97 m3·mol-1 Chemaxon Polarizability 21.17 Å3 Chemaxon Number of Rings 1 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
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9382 Caco-2 permeable + 0.7357 P-glycoprotein substrate Non-substrate 0.6711 P-glycoprotein inhibitor I Non-inhibitor 0.8781 P-glycoprotein inhibitor II Non-inhibitor 0.9484 Renal organic cation transporter Non-inhibitor 0.7849 CYP450 2C9 substrate Non-substrate 0.8191 CYP450 2D6 substrate Substrate 0.8918 CYP450 3A4 substrate Non-substrate 0.5463 CYP450 1A2 substrate Inhibitor 0.9107 CYP450 2C9 inhibitor Non-inhibitor 0.941 CYP450 2D6 inhibitor Inhibitor 0.8932 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor Non-inhibitor 0.9132 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6004 Ames test Non AMES toxic 0.6357 Carcinogenicity Non-carcinogens 0.7796 Biodegradation Not ready biodegradable 0.9261 Rat acute toxicity 2.6338 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8982 hERG inhibition (predictor II) Non-inhibitor 0.6563
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 146.7579364 predictedDarkChem Lite v0.1.0 [M-H]- 139.24828 predictedDeepCCS 1.0 (2019) [M+H]+ 147.3383364 predictedDarkChem Lite v0.1.0 [M+H]+ 141.89243 predictedDeepCCS 1.0 (2019) [M+Na]+ 146.5748364 predictedDarkChem Lite v0.1.0 [M+Na]+ 150.57631 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Pore-forming subunit of Nav1.5, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient. The influx of Na(+) ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues (PubMed:1309946, PubMed:21447824, PubMed:23085483, PubMed:23420830, PubMed:25370050, PubMed:26279430, PubMed:26392562, PubMed:26776555). Nav1.5 is the predominant sodium channel expressed in myocardial cells and it is responsible for the initial upstroke of the action potential in cardiac myocytes, thereby initiating the heartbeat (PubMed:11234013, PubMed:11804990, PubMed:12569159, PubMed:1309946). Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2 (By similarity)
- Specific Function
- ankyrin binding
- Gene Name
- SCN5A
- Uniprot ID
- Q14524
- Uniprot Name
- Sodium channel protein type 5 subunit alpha
- Molecular Weight
- 226937.475 Da
References
- Valdivia CR, Ackerman MJ, Tester DJ, Wada T, McCormack J, Ye B, Makielski JC: A novel SCN5A arrhythmia mutation, M1766L, with expression defect rescued by mexiletine. Cardiovasc Res. 2002 Aug 1;55(2):279-89. [Article]
- Chinushi M, Tagawa M, Sugiura H, Komura S, Hosaka Y, Washizuka T, Aizawa Y: Ventricular tachyarrhythmias in a canine model of LQT3: arrhythmogenic effects of sympathetic activity and therapeutic effects of mexiletine. Circ J. 2003 Mar;67(3):263-8. [Article]
- Fabritz L, Kirchhof P, Franz MR, Nuyens D, Rossenbacker T, Ottenhof A, Haverkamp W, Breithardt G, Carmeliet E, Carmeliet P: Effect of pacing and mexiletine on dispersion of repolarisation and arrhythmias in DeltaKPQ SCN5A (long QT3) mice. Cardiovasc Res. 2003 Mar 15;57(4):1085-93. [Article]
- Wang HW, Zheng YQ, Yang ZF, Li CZ, Liu YM: Effect of mexiletine on long QT syndrome model. Acta Pharmacol Sin. 2003 Apr;24(4):316-20. [Article]
- Napolitano C, Bloise R, Priori SG: Gene-specific therapy for inherited arrhythmogenic diseases. Pharmacol Ther. 2006 Apr;110(1):1-13. Epub 2005 Sep 15. [Article]
- Shimizu W, Antzelevitch C, Suyama K, Kurita T, Taguchi A, Aihara N, Takaki H, Sunagawa K, Kamakura S: Effect of sodium channel blockers on ST segment, QRS duration, and corrected QT interval in patients with Brugada syndrome. J Cardiovasc Electrophysiol. 2000 Dec;11(12):1320-9. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Ligand-activated transcription factor that enables cells to adapt to changing conditions by sensing compounds from the environment, diet, microbiome and cellular metabolism, and which plays important roles in development, immunity and cancer (PubMed:23275542, PubMed:30373764, PubMed:32818467, PubMed:7961644). Upon ligand binding, translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE) (PubMed:23275542, PubMed:30373764, PubMed:7961644). Regulates a variety of biological processes, including angiogenesis, hematopoiesis, drug and lipid metabolism, cell motility and immune modulation (PubMed:12213388). Xenobiotics can act as ligands: upon xenobiotic-binding, activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene) (PubMed:7961644). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons (PubMed:34521881, PubMed:7961644). Next to xenobiotics, natural ligands derived from plants, microbiota, and endogenous metabolism are potent AHR agonists (PubMed:18076143). Tryptophan (Trp) derivatives constitute an important class of endogenous AHR ligands (PubMed:32818467, PubMed:32866000). Acts as a negative regulator of anti-tumor immunity: indoles and kynurenic acid generated by Trp catabolism act as ligand and activate AHR, thereby promoting AHR-driven cancer cell motility and suppressing adaptive immunity (PubMed:32818467). Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1 (PubMed:28602820). Inhibits PER1 by repressing the CLOCK-BMAL1 heterodimer mediated transcriptional activation of PER1 (PubMed:28602820). The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28602820)
- Specific Function
- cis-regulatory region sequence-specific DNA binding
- Gene Name
- AHR
- Uniprot ID
- P35869
- Uniprot Name
- Aryl hydrocarbon receptor
- Molecular Weight
- 96146.705 Da
References
- Hu W, Sorrentino C, Denison MS, Kolaja K, Fielden MR: Induction of cyp1a1 is a nonspecific biomarker of aryl hydrocarbon receptor activation: results of large scale screening of pharmaceuticals and toxicants in vivo and in vitro. Mol Pharmacol. 2007 Jun;71(6):1475-86. Epub 2007 Feb 27. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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
- Labbe L, Abolfathi Z, Lessard E, Pakdel H, Beaune P, Turgeon J: Role of specific cytochrome P450 enzymes in the N-oxidation of the antiarrhythmic agent mexiletine. Xenobiotica. 2003 Jan;33(1):13-25. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). 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:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable)
- Specific Function
- 4-nitrophenol 2-monooxygenase activity
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- Labbe L, Abolfathi Z, Lessard E, Pakdel H, Beaune P, Turgeon J: Role of specific cytochrome P450 enzymes in the N-oxidation of the antiarrhythmic agent mexiletine. Xenobiotica. 2003 Jan;33(1):13-25. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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
- Labbe L, O'Hara G, Lefebvre M, Lessard E, Gilbert M, Adedoyin A, Champagne J, Hamelin B, Turgeon J: Pharmacokinetic and pharmacodynamic interaction between mexiletine and propafenone in human beings. Clin Pharmacol Ther. 2000 Jul;68(1):44-57. doi: 10.1067/mcp.2000.108023. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- Nakajima M, Kobayashi K, Shimada N, Tokudome S, Yamamoto T, Kuroiwa Y: Involvement of CYP1A2 in mexiletine metabolism. Br J Clin Pharmacol. 1998 Jul;46(1):55-62. [Article]
- Wei X, Dai R, Zhai S, Thummel KE, Friedman FK, Vestal RE: Inhibition of human liver cytochrome P-450 1A2 by the class IB antiarrhythmics mexiletine, lidocaine, and tocainide. J Pharmacol Exp Ther. 1999 May;289(2):853-8. [Article]
- Flockhart Table of Drug Interactions [Link]
- Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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
- Nakajima M, Kobayashi K, Shimada N, Tokudome S, Yamamoto T, Kuroiwa Y: Involvement of CYP1A2 in mexiletine metabolism. Br J Clin Pharmacol. 1998 Jul;46(1):55-62. [Article]
- Otani M, Fukuda T, Naohara M, Maune H, Senda C, Yamamoto I, Azuma J: Impact of CYP2D6*10 on mexiletine pharmacokinetics in healthy adult volunteers. Eur J Clin Pharmacol. 2003 Sep;59(5-6):395-9. doi: 10.1007/s00228-003-0656-5. Epub 2003 Aug 23. [Article]
- Senda C, Yamaura Y, Kobayashi K, Fujii H, Minami H, Sasaki Y, Igarashi T, Chiba K: Influence of the CYP2D6*10 allele on the metabolism of mexiletine by human liver microsomes. Br J Clin Pharmacol. 2001 Jul;52(1):100-3. doi: 10.1046/j.0306-5251.2001.01411.x. [Article]
- Flockhart Table of Drug Interactions [Link]
Drug created at June 13, 2005 13:24 / Updated at October 29, 2024 18:19