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Identification
- Summary
Eslicarbazepine acetate is an anticonvulsant agent used as an adjunct to treat partial-onset seizures in patients with inadequate clinical response to conventional antiepileptic therapy.
- Brand Names
- Aptiom, Zebinix
- Generic Name
- Eslicarbazepine acetate
- DrugBank Accession Number
- DB09119
- Background
Eslicarbazepine acetate (ESL) is an anticonvulsant medication approved for use in Europe, the United States and Canada as an adjunctive therapy for partial-onset seizures that are not adequately controlled with conventional therapy. Eslicarbazepine acetate is a prodrug that is rapidly converted to eslicarbazepine, the primary active metabolite in the body. Eslicarbazepine's mechanism of action is not well understood, but it is known that it does exert anticonvulsant activity by inhibiting repeated neuronal firing and stabilizing the inactivated state of voltage-gated sodium channels, thus preventing their return to the activated state during which seizure activity can occur.
Eslicarbazepine acetate is marketed as Aptiom in North America and Zebinix or Exalief in Europe. It is available in 200, 400, 600, or 800mg tablets that are taken once daily, with or without food. Eslicarbazepine acetate is associated with numerous side effects including dizziness, drowsiness, nausea, vomiting, diarrhea, headache, aphasia, lack of concentration, psychomotor retardation, speech disturbances, ataxia, depression and hyponatremia. It is recommended that patients taking eslicarbazepine acetate be monitored for suicidality.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Eslicarbazepine acetate (DB09119)
- Weight
- Average: 296.326
Monoisotopic: 296.116092383 - Chemical Formula
- C17H16N2O3
- Synonyms
- (10S)-10-acetoxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide
- (10S)-5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl acetate
- ESL
- Eslicarbazepine acetate
- External IDs
- BIA 2-093
- BIA-2-093
- BIA2-093
- SEP 0002093
- SEP-0002093
- SEP0002093
Pharmacology
- Indication
Eslicarbazepine acetate is indicated for the treatment of partial-onset seizures in patients 4 years of age and older.13
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Partial-onset seizures •••••••••••• •••••• - 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
Eslicarbazepine acetate is associated with a dose- and concentration-dependant increase in heart rate and prolongation of PR interval.
- Mechanism of action
Eslicarbazepine acetate is converted to the active metabolite eslicarbazepine which carries out its anticonvulsant activity. The exact mechanism of action is unknown, but it is thought to involve the inhibition of voltage-gated sodium channels. In in vitro electrophysiological studies, eslicarbazepine was shown to inhibit repeated neuronal firing by stabilizing the inactivated state of voltage-gated sodium channels and preventing their return to the activated state. In vitro studies also showed eslicarbazepine inhibiting T-type calcium channels, which likely also has a role in anticonvulsant activity.
Target Actions Organism AP2X purinoceptor 4 antagonistHumans - Absorption
Eslicarbazepine active metabolite has a high bioavailability and reaches peak serum concentration 1-4 hours after a given dose. Eslicarbazepine acetate absorption is not affected by food.
- Volume of distribution
The apparent volume of distribution of eslicarbazepine is 61.3 L for a body weight of 70 kg based on population PK analysis.
- Protein binding
Eslicarbazepine is bound to plasma proteins at a relatively low rate of <40%, independent of concentration. In vitro studies have shown that plasma protein binding is not relevantly affected by the presence of other medications such as warfarin, diazepam, digoxin, phenytoin or tolbutamide. Similarly, the binding of these medications was not significantly affected by the presence of eslicarbazepine.
- Metabolism
Eslicarbazepine acetate is rapidly and extensively metabolized to its major active metabolite, eslicarbazepine, via hydrolytic first-pass metabolism. Eslicarbazepine corresponds to about 92% of systemic exposure. Minor active metabolites (R)-licarbazepine and oxcarbazepine consist of <5% of systemic exposure. Active metabolites are then metabolized to inactive glucuronides that correspond to about 3% of systemic exposure.
Eslicarbazepine had a moderate inhibitory effect on CYP2C19 and a mild activation of UGT1A1-mediated glucuronidation when studied in human hepatic microsomes. It has been shown to induce CYP3A4 enzymes in vivo.
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- Route of elimination
Eslicarbazepine acetate and its metabolites are eliminated primarily via renal excretion. Eslicarbazepine active metabolite is excreted two-thirds in the unchanged form and one-third as a glucuronide conjugate. This accounts for around 90% of total metabolites excreted, with the remaining 10% being minor metabolites. Renal tubular reabsorption is expected to occur with eslicarbazepine.
- Half-life
The apparent plasma half-life of eslicarbazepine is 10-20 hours in healthy subjects and 13-20 hours in epilepsy patients. Steady-state plasma concentrations are attained after 4 to 5 days of once daily dosing.
- Clearance
Renal clearance of eslicarbazepine was found to be approximately 20 mL/min in healthy subjects with normal renal function.
- Adverse Effects
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There are no adequate and well-controlled studies of the use of eslicarbazepine acetate in pregnant women. In studies conducted in pregnant mice, rats, and rabbits, eslicarbazepine acetate did show developmental toxicities, including teratogenicity, embryolethality, and fetal growth retardation, at clinically relevant doses. Drug-induced liver injury ranging from mild to moderate elevations in transaminases (>3 times the upper limit of normal) to rare cases with concomitant elevations of total bilirubin (>2 times the upper limit of normal) have been reported with the use of eslicarbazepine. Overdose with eslicarbazepine acetate appears similar to its known adverse reactions and includes symptoms of hyponatremia, dizziness, nausea, vomiting, somnolence, euphoria, oral paraesthesias, ataxia, and diplopia. There is no specific antidote for eslicarbazepine acetate overdose and it should be treated primarily with supportive measures. If required, the drug may be removed by gastric lavage, partially by hemodialysis or inactivated with activated charcoal.
- 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 CNS depression can be increased when Eslicarbazepine acetate is combined with 1,2-Benzodiazepine. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Eslicarbazepine acetate. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Eslicarbazepine acetate. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Eslicarbazepine acetate. Acenocoumarol The metabolism of Acenocoumarol can be increased when combined with Eslicarbazepine acetate. - Food Interactions
- Take with or without food.
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.- Active Moieties
Name Kind UNII CAS InChI Key Eslicarbazepine prodrug S5VXA428R4 104746-04-5 BMPDWHIDQYTSHX-AWEZNQCLSA-N - International/Other Brands
- Eksaliyef (Bial-Portela & Ca. S.A.) / Erelib (Bial-Portela & Ca. S.A.) / Eslicar (Emcure Pharmaceuticals Ltd) / Eslify (Torrent Pharmaceuticals Ltd) / Eslistar (Lupin Ltd) / Eslizen (Intas Pharmaceuticals Ltd) / Exalief (Bial-Portela & Ca. S.A.) / Normictal (Abbott India Ltd) / Stedesa / Zefretol (Sun Pharma Laboratories Ltd)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Aptiom Tablet 200 mg Oral Sumitomo Pharma America, Inc. 2014-08-07 Not applicable Canada 
Aptiom Tablet 200 mg/1 Oral Sumitomo Pharma America, Inc. 2014-04-07 Not applicable US 
Aptiom Tablet 800 mg Oral Sumitomo Pharma America, Inc. 2014-08-07 Not applicable Canada Aptiom Tablet 600 mg/1 Oral Sumitomo Pharma America, Inc. 2014-04-07 Not applicable US Aptiom Tablet 800 mg/1 Oral Sumitomo Pharma America, Inc. 2014-04-07 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Eslicarbazepine acetate Tablet 200 mg/1 Oral Camber Pharmaceuticals, Inc. 2023-08-03 Not applicable US Eslicarbazepine acetate Tablet 600 mg/1 Oral Camber Pharmaceuticals, Inc. 2023-08-03 Not applicable US Eslicarbazepine acetate Tablet 800 mg/1 Oral Camber Pharmaceuticals, Inc. 2023-08-03 Not applicable US Eslicarbazepine acetate Tablet 400 mg/1 Oral Camber Pharmaceuticals, Inc. 2023-08-03 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Aptiom Eslicarbazepine acetate (400 mg/1) + Eslicarbazepine acetate (800 mg/1) Kit Oral Sumitomo Pharma America, Inc. 2014-04-07 Not applicable US Aptiom Eslicarbazepine acetate (400 mg/1) + Eslicarbazepine acetate (800 mg/1) Kit Oral Sumitomo Pharma America, Inc. 2014-04-07 Not applicable US
Categories
- Drug Categories
- Anticonvulsants
- Carboxamide Derivatives
- Cardiovascular Agents
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 Inhibitors (moderate)
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (weak)
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Eslicarbazepine and prodrugs
- Heterocyclic Compounds, Fused-Ring
- Membrane Transport Modulators
- Nervous System
- Sodium Channel Blockers
- UGT1A1 Substrates
- Voltage-Gated Sodium Channel Blockers
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as dibenzazepines. These are compounds with two benzene rings connected by an azepine ring. Azepine is an unsaturated seven-member heterocycle with one nitrogen atom replacing a carbon atom.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Benzazepines
- Sub Class
- Dibenzazepines
- Direct Parent
- Dibenzazepines
- Alternative Parents
- Azepines / Benzenoids / Ureas / Carboxylic acid esters / Monocarboxylic acids and derivatives / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives show 1 more
- Substituents
- Aromatic heteropolycyclic compound / Azacycle / Azepine / Benzenoid / Carbonic acid derivative / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Dibenzazepine / Hydrocarbon derivative show 8 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- acetate ester, carboxamide, dibenzoazepine (CHEBI:87016)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- BEA68ZVB2K
- CAS number
- 236395-14-5
- InChI Key
- QIALRBLEEWJACW-INIZCTEOSA-N
- InChI
- InChI=1S/C17H16N2O3/c1-11(20)22-16-10-12-6-2-4-8-14(12)19(17(18)21)15-9-5-3-7-13(15)16/h2-9,16H,10H2,1H3,(H2,18,21)/t16-/m0/s1
- IUPAC Name
- (9S)-2-carbamoyl-2-azatricyclo[9.4.0.0³,⁸]pentadeca-1(15),3,5,7,11,13-hexaen-9-yl acetate
- SMILES
- CC(=O)O[C@H]1CC2=CC=CC=C2N(C(N)=O)C2=CC=CC=C12
References
- Synthesis Reference
- Ravinder B, Reddy SR, Sridhar M, Mohan MM, Srinivas K, Reddy AP, Bandichhor R. An efficient synthesis for eslicarbazepine acetate, oxcarbazepine, and carbamazepine. Tetrahedron Letters. 2013 May 29;54(22):2841-4.
- Desai S, Poddar A, Sawant K: Formulation of cyclodextrin inclusion complex-based orally disintegrating tablet of eslicarbazepine acetate for improved oral bioavailability. Mater Sci Eng C Mater Biol Appl. 2016 Jan 1;58:826-34. doi: 10.1016/j.msec.2015.09.019. Epub 2015 Sep 8. Pubmed.
- General References
- Banach M, Borowicz KK, Czuczwar SJ: Pharmacokinetic/pharmacodynamic evaluation of eslicarbazepine for the treatment of epilepsy. Expert Opin Drug Metab Toxicol. 2015 Apr;11(4):639-48. doi: 10.1517/17425255.2015.1021686. Epub 2015 Mar 5. [Article]
- Bialer M, White HS: Key factors in the discovery and development of new antiepileptic drugs. Nat Rev Drug Discov. 2010 Jan;9(1):68-82. doi: 10.1038/nrd2997. [Article]
- Bialer M, Soares-da-Silva P: Pharmacokinetics and drug interactions of eslicarbazepine acetate. Epilepsia. 2012 Jun;53(6):935-46. doi: 10.1111/j.1528-1167.2012.03519.x. Epub 2012 May 21. [Article]
- Villanueva V, Serratosa JM, Guillamon E, Garces M, Giraldez BG, Toledo M, Salas-Puig J, Lopez Gonzalez FJ, Flores J, Rodriguez-Uranga J, Castillo A, Mauri JA, Camacho JL, Lopez-Gomariz E, Giner P, Torres N, Palau J, Molins A: Long-term safety and efficacy of eslicarbazepine acetate in patients with focal seizures: results of the 1-year ESLIBASE retrospective study. Epilepsy Res. 2014 Sep;108(7):1243-52. doi: 10.1016/j.eplepsyres.2014.04.014. Epub 2014 May 14. [Article]
- Soares-da-Silva P, Pires N, Bonifacio MJ, Loureiro AI, Palma N, Wright LC: Eslicarbazepine acetate for the treatment of focal epilepsy: an update on its proposed mechanisms of action. Pharmacol Res Perspect. 2015 Mar;3(2):e00124. doi: 10.1002/prp2.124. Epub 2015 Mar 30. [Article]
- Rocamora R: A review of the efficacy and safety of eslicarbazepine acetate in the management of partial-onset seizures. Ther Adv Neurol Disord. 2015 Jul;8(4):178-86. doi: 10.1177/1756285615589711. [Article]
- Tomic MA, Pecikoza UB, Micov AM, Stepanovic-Petrovic RM: The Efficacy of Eslicarbazepine Acetate in Models of Trigeminal, Neuropathic, and Visceral Pain: The Involvement of 5-HT1B/1D Serotonergic and CB1/CB2 Cannabinoid Receptors. Anesth Analg. 2015 Dec;121(6):1632-9. doi: 10.1213/ANE.0000000000000953. [Article]
- Jacobson MP, Pazdera L, Bhatia P, Grinnell T, Cheng H, Blum D: Efficacy and safety of conversion to monotherapy with eslicarbazepine acetate in adults with uncontrolled partial-onset seizures: a historical-control phase III study. BMC Neurol. 2015 Mar 28;15:46. doi: 10.1186/s12883-015-0305-5. [Article]
- Zaccara G, Giovannelli F, Cincotta M, Carelli A, Verrotti A: Clinical utility of eslicarbazepine: current evidence. Drug Des Devel Ther. 2015 Feb 10;9:781-9. doi: 10.2147/DDDT.S57409. eCollection 2015. [Article]
- Sperling MR, Abou-Khalil B, Harvey J, Rogin JB, Biraben A, Galimberti CA, Kowacs PA, Hong SB, Cheng H, Blum D, Nunes T, Soares-da-Silva P: Eslicarbazepine acetate as adjunctive therapy in patients with uncontrolled partial-onset seizures: Results of a phase III, double-blind, randomized, placebo-controlled trial. Epilepsia. 2015 Feb;56(2):244-53. doi: 10.1111/epi.12894. Epub 2014 Dec 22. [Article]
- Shaikh S, Rizvi SM, Hameed N, Biswas D, Khan M, Shakil S, Kamal MA: Aptiom (eslicarbazepine acetate) as a dual inhibitor of beta-secretase and voltage-gated sodium channel: advancement in Alzheimer's disease-epilepsy linkage via an enzoinformatics study. CNS Neurol Disord Drug Targets. 2014;13(7):1258-62. [Article]
- Doeser A, Soares-da-Silva P, Beck H, Uebachs M: The effects of eslicarbazepine on persistent Na(+) current and the role of the Na(+) channel beta subunits. Epilepsy Res. 2014 Feb;108(2):202-11. doi: 10.1016/j.eplepsyres.2013.11.022. Epub 2013 Dec 8. [Article]
- FDA Approved Drug Products: Aptiom (eslicarbazepine acetate) tablets for oral use [Link]
- External Links
- KEGG Drug
- D09612
- PubChem Compound
- 179344
- PubChem Substance
- 310265036
- ChemSpider
- 156110
- BindingDB
- 50240669
- 1482501
- ChEBI
- 87016
- ChEMBL
- CHEMBL87992
- ZINC
- ZINC000000007295
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Eslicarbazepine_acetate
- FDA label
- Download (820 KB)
- MSDS
- Download (44.8 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 Completed Not Available Epilepsy 2 somestatus stop reason just information to hide Not Available Completed Not Available Partial-Onset Seizures 1 somestatus stop reason just information to hide Not Available Unknown Status Not Available Aging / Aging Disorder / Epilepsy / Epilepsy; Seizure 1 somestatus stop reason just information to hide 4 Completed Treatment Epilepsy 1 somestatus stop reason just information to hide 4 Completed Treatment Partial-Onset Seizures 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Kit Oral Tablet Oral 200 mg Tablet Oral 200 mg/1 Tablet Oral 400 mg/1 Tablet Oral 400 mg Tablet Oral 600 mg/1 Tablet Oral 600 mg Tablet Oral 800 mg/1 Tablet Oral 800 MG Suspension Oral 50 MG/ML - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5753646 No 1998-05-19 2016-06-27 US US8372431 No 2013-02-12 2030-04-17 US US9206135 No 2015-12-08 2026-04-21 US US9643929 No 2017-05-09 2026-04-21 US US9566244 No 2017-02-14 2028-10-23 US US9763954 No 2017-09-19 2028-09-13 US US9750747 No 2017-09-05 2032-08-24 US US10695354 No 2020-06-30 2025-05-06 US US10675287 No 2020-06-09 2025-05-06 US US10702536 No 2020-07-07 2025-05-06 US US10912781 No 2021-02-09 2028-10-23 US US11364247 No 2005-05-06 2025-05-06 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Water solubility of eslicarbazepine acetate is low at less than 1 mg/mL including at different pH values. Its main metabolite eslicarbazepine has a greater water solubility of 4.2 mg/mL. # Banach M, Borowicz KK, Czuczwar SJ: Pharmacokinetic/pharmacodynamic evaluation of eslicarbazepine for the treatment of epilepsy. Expert Opin Drug Metab Toxicol. 2015 Apr;11(4):639-48. doi: 10.1517/17425255.2015.1021686. Epub 2015 Mar 5. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/25740561 logP 8.8 # Bialer M, Soares-da-Silva P: Pharmacokinetics and drug interactions of eslicarbazepine acetate. Epilepsia. 2012 Jun;53(6):935-46. doi: 10.1111/j.1528-1167.2012.03519.x. Epub 2012 May 21. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/22612290 - Predicted Properties
Property Value Source Water Solubility 0.11 mg/mL ALOGPS logP 1.99 ALOGPS logP 2.17 Chemaxon logS -3.4 ALOGPS pKa (Strongest Acidic) 15.96 Chemaxon pKa (Strongest Basic) -3.8 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 72.63 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 81.44 m3·mol-1 Chemaxon Polarizability 30.19 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No 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 splash10-000l-4290000000-ce88828aa8458d5001cf Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-000b-0190000000-7af1e0dfe0325ae3ab4a Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4i-9100000000-aa98df9e1fa47b1e2c74 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-01p6-0490000000-4ede23df8099b65574d0 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4i-9000000000-06464f476e9b46a53d83 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-0490000000-5d275ffc6cc7e404595d Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-052f-9000000000-dc41dbb452f3d9a806b4 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]- 179.0404472 predictedDarkChem Lite v0.1.0 [M-H]- 161.73204 predictedDeepCCS 1.0 (2019) [M+H]+ 179.9304472 predictedDarkChem Lite v0.1.0 [M+H]+ 164.09009 predictedDeepCCS 1.0 (2019) [M+Na]+ 179.4916472 predictedDarkChem Lite v0.1.0 [M+Na]+ 170.35072 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- ATP-gated nonselective transmembrane cation channel permeable to potassium, sodium and calcium (PubMed:9016352). CTP, but not GTP or UTP, functions as a weak affinity agonist for P2RX4 (By similarity). Activated by extracellularly released ATP, it plays multiple role in immunity and central nervous system physiology (PubMed:35165166). Plays a key role in initial steps of T-cell activation and Ca(2+) microdomain formation (By similarity). Participates also in basal T-cell activity without TCR/CD3 stimulation (By similarity). Promotes the differentiation and activation of Th17 cells via expression of retinoic acid-related orphan receptor C/RORC (PubMed:35165166). Upon activation, drives microglia motility via the PI3K/Akt pathway (By similarity). Could also function as an ATP-gated cation channel of lysosomal membranes (By similarity)
- Specific Function
- ATP binding
- Gene Name
- P2RX4
- Uniprot ID
- Q99571
- Uniprot Name
- P2X purinoceptor 4
- Molecular Weight
- 43368.725 Da
References
- Tian M, Abdelrahman A, Weinhausen S, Hinz S, Weyer S, Dosa S, El-Tayeb A, Muller CE: Carbamazepine derivatives with P2X4 receptor-blocking activity. Bioorg Med Chem. 2014 Feb 1;22(3):1077-88. doi: 10.1016/j.bmc.2013.12.035. Epub 2013 Dec 25. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). 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:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
- Specific Function
- (R)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55944.565 Da
References
- Bialer M, Soares-da-Silva P: Pharmacokinetics and drug interactions of eslicarbazepine acetate. Epilepsia. 2012 Jun;53(6):935-46. doi: 10.1111/j.1528-1167.2012.03519.x. Epub 2012 May 21. [Article]
- Bialer M, White HS: Key factors in the discovery and development of new antiepileptic drugs. Nat Rev Drug Discov. 2010 Jan;9(1):68-82. doi: 10.1038/nrd2997. [Article]
- Galiana GL, Gauthier AC, Mattson RH: Eslicarbazepine Acetate: A New Improvement on a Classic Drug Family for the Treatment of Partial-Onset Seizures. Drugs R D. 2017 Sep;17(3):329-339. doi: 10.1007/s40268-017-0197-5. [Article]
- Eslicarbazepine, PDR [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inducer
- 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
- Bialer M, Soares-da-Silva P: Pharmacokinetics and drug interactions of eslicarbazepine acetate. Epilepsia. 2012 Jun;53(6):935-46. doi: 10.1111/j.1528-1167.2012.03519.x. Epub 2012 May 21. [Article]
- Bialer M, White HS: Key factors in the discovery and development of new antiepileptic drugs. Nat Rev Drug Discov. 2010 Jan;9(1):68-82. doi: 10.1038/nrd2997. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- Curator comments
- The FDA label reports a mild activation of UGT1A1- mediated glucuronidation was observed in human hepatic microsomes, in relation to eslicarbazepine metabolism.
- 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:15472229, PubMed:18004206, PubMed:18004212, PubMed:18719240, PubMed:19830808, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004206, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:15472229, PubMed:18719240, PubMed:23288867). Involved in the glucuronidation of bilirubin, a degradation product occurring in the normal catabolic pathway that breaks down heme in vertebrates (PubMed:17187418, PubMed:18004206, PubMed:19830808, PubMed:24525562). Also catalyzes the glucuronidation 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 losartan, 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:18004212, PubMed:20610558)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A1
- Uniprot ID
- P22309
- Uniprot Name
- UDP-glucuronosyltransferase 1A1
- Molecular Weight
- 59590.91 Da
References
- FDA Approved Drug Products: Aptiom (eslicarbazepine acetate) tablets for oral use [Link]
Drug created at September 22, 2015 20:02 / Updated at April 23, 2024 11:38