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Identification
NameEzogabine
Accession NumberDB04953
TypeSmall Molecule
GroupsApproved
DescriptionEzogabine (D23129) is a close structural analog of the centrally acting analgesic flupitrine. It is a neuronal potassium channel opener being developed as a first-in-class antiepileptic drug (AED) and is currently being studied in Phase 3 trials as an adjunctive treatment for partial-onset seizures in adult patients with refractory epilepsy. FDA approved in June 10, 2011 under the name of ezogabine.
Structure
Thumb
Synonyms
D-23129
Ethyl {2-amino-4-[(4-fluorobenzyl)amino]phenyl}carbamate
Ethyl 2-amino-4-((P-fluorobenzyl)amino)carbanilate
EZG
N-(2-Amino-4-(4-fluorobenzylamino)-phenyl) carbamic acid ethyl ester
N-(2-Amino-4-(4-fluorobenzylamino)phenyl)carbamic acid ethyl ester
Potiga
Retigabine
RTG
External Identifiers
  • D-23129
  • D23129
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Potigatablet, film coated50 mg/1oralGlaxo Smith Kline Llc2012-04-19Not applicableUs
Potigatablet, film coated200 mg/1oralGlaxo Smith Kline Llc2012-04-19Not applicableUs
Potigatablet, film coated300 mg/1oralGlaxo Smith Kline Llc2012-04-19Not applicableUs
Potigatablet, film coated400 mg/1oralGlaxo Smith Kline Llc2012-04-19Not applicableUs
TrobaltFilm-coated tablet100 mgOral useGlaxo Group Limited  2011-03-28Not applicableEu
TrobaltFilm-coated tablet300 mgOral useGlaxo Group Limited  2011-03-28Not applicableEu
TrobaltFilm-coated tablet50 mgOral useGlaxo Group Limited  2011-03-28Not applicableEu
TrobaltFilm-coated tablet200 mgOral useGlaxo Group Limited  2011-03-28Not applicableEu
TrobaltFilm-coated tablet400 mgOral useGlaxo Group Limited  2011-03-28Not applicableEu
TrobaltFilm-coated tablet50 mgOral useGlaxo Group Limited  2011-03-28Not applicableEu
TrobaltFilm-coated tablet200 mgOral useGlaxo Group Limited  2011-03-28Not applicableEu
TrobaltFilm-coated tablet400 mgOral useGlaxo Group Limited  2011-03-28Not applicableEu
TrobaltFilm-coated tablet100 mgOral useGlaxo Group Limited  2011-03-28Not applicableEu
TrobaltFilm-coated tablet300 mgOral useGlaxo Group Limited  2011-03-28Not applicableEu
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII12G01I6BBU
CAS number150812-12-7
WeightAverage: 303.3314
Monoisotopic: 303.13830504
Chemical FormulaC16H18FN3O2
InChI KeyInChIKey=PCOBBVZJEWWZFR-UHFFFAOYSA-N
InChI
InChI=1S/C16H18FN3O2/c1-2-22-16(21)20-15-8-7-13(9-14(15)18)19-10-11-3-5-12(17)6-4-11/h3-9,19H,2,10,18H2,1H3,(H,20,21)
IUPAC Name
ethyl N-(2-amino-4-{[(4-fluorophenyl)methyl]amino}phenyl)carbamate
SMILES
CCOC(=O)NC1=C(N)C=C(NCC2=CC=C(F)C=C2)C=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylcarbamates. These are compounds containing a phenylazide moiety, which consists of a carbamic acid substituent attached to a phenyl group.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenylcarbamates
Direct ParentPhenylcarbamates
Alternative Parents
Substituents
  • Phenylcarbamate
  • Phenylalkylamine
  • Substituted aniline
  • Phenylmethylamine
  • Benzylamine
  • Aralkylamine
  • Secondary aliphatic/aromatic amine
  • Halobenzene
  • Fluorobenzene
  • Aniline
  • Primary aromatic amine
  • Aryl halide
  • Aryl fluoride
  • Secondary amine
  • Monocarboxylic acid or derivatives
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationAdjuvant treatment of partial-onset seizures.
PharmacodynamicsAs compared to other antiepileptic agents, ezogabine is unique in that it selectively activates potassium ion channels Kv 7.2-Kv7.5 and not cardiac Kv 7.1, thereby avoiding cardiac side effects. The antiepileptics, as a drug class, are routinely used in the treatment of a number of disease states in addition to epilepsy. Ezogabine is highly efficacious in a broad-spectrum of in vivo epilepsy and seizure models. A comparison of antiepileptic form activity of ezogabine with that of conventional anticonvulsants in in vitro models suggests that retigabine is especially likely to be useful in the treatment of pharmacoresistant epilepsy. Retigabine clearly attenuates pain-like behaviors in various animal models of neuropathic pain; it may also prove to be useful in treatment of clinical anxiety disorders. Clinical data obtained thus far indicate that retigabine is well tolerated in humans when titrated up to its therapeutic dose range. No tolerance, drug dependence, or withdrawal liability has been reported. Thus, retigabine may prove to be useful in the treatment of a diverse range of disease states in which neuronal hyperexcitability is a common underlying factor.
Mechanism of actionEzogabine has a novel mechanism of action that involves opening of neuronal Kv7.2-7.5 (formerly KCNQ2-5) voltage activated potassium channels. These channels (primarily Kv7.2/7.3) enable generation of the M-current, a sub-threshold potassium current that serves to stabilize the membrane potential and control neuronal excitability. In addition to acting on potassium ion channels, retigabine also affects GABA neurotransmission in the GABA-A receptor, which is a key inhibitory receptor in the central nervous system and is implicated in epilepsy. Malfunctioning of the GABA-A receptor leads to hyperexcitability in the brain, which causes seizures, making this receptor an important target for antiepileptic therapeutics. Apart from increasing the concentration of GABA in the brain (by either enhancing GABA synthesis or blocking GABA metabolism), retigabine allosterically potentiates GABA-induced current in rat cortical neurons in a concentration-dependent manner. Numerous studies have demonstrated that retigabine is effective in a broad spectrum of in vivo epilepsy and seizure models.
Related Articles
AbsorptionRapidly absorbed and distributed, with an absolute oral bioavailability of 60%. Pharmacokinetics of ezogabine suggest first-order kinetics. Tmax, single oral dose = 30-120 minutes; Time to steady state = 3 days
Volume of distribution

8.7 L/kg

Protein bindingApproximately 80% protein bound.
Metabolism

Ezogabine is metabolized exclusively via phase II hepatic N-glucurodination and acetylation. N-glucurodination is the major metabolic pathway of the two and form two major N-glucuronide metabolites. The enzymes involved are UGT1A1, 1A9, 1A4, and 1A3. However, the product of the N-acetyl pathway is a weak, active metabolite referred to as NAMR. The enzyme that is involved in the N-acetyl pathway is called N-acetyltransferase 2. The pharmacokinetics of NAMR and ezogabine are similar. The cytochrome P450 enzyme system is not involved with the metabolism of ezogabine.

Route of eliminationUrine (85%, 36% of total dose as unchanged drug, 18% of total dose as NAMR) and feces (14%, 3% of total dose as unchanged drug)
Half lifeTerminal half-life = 7.5 hours
Clearance

0.58 – 0.76 L/h·kg. Clearance may differ between ethnic groups with Black Americans having 20% lower clearance than Caucasian Americans.

ToxicityLethal Dose, acute, oral, rat = 100 mg/kg; Lethal Dose, chronic, oral, rat = 5.1 mg/kg/day, 90-day; Most common adverse effects that lead to discontinuation of therapy include dizziness and somnolence.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9876
Blood Brain Barrier+0.9382
Caco-2 permeable-0.5245
P-glycoprotein substrateNon-substrate0.5295
P-glycoprotein inhibitor INon-inhibitor0.6642
P-glycoprotein inhibitor IINon-inhibitor0.9155
Renal organic cation transporterNon-inhibitor0.8998
CYP450 2C9 substrateNon-substrate0.8602
CYP450 2D6 substrateNon-substrate0.8045
CYP450 3A4 substrateNon-substrate0.679
CYP450 1A2 substrateInhibitor0.8417
CYP450 2C9 inhibitorNon-inhibitor0.607
CYP450 2D6 inhibitorInhibitor0.5995
CYP450 2C19 inhibitorNon-inhibitor0.5221
CYP450 3A4 inhibitorInhibitor0.5085
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6414
Ames testNon AMES toxic0.5119
CarcinogenicityNon-carcinogens0.621
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.4793 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9807
hERG inhibition (predictor II)Non-inhibitor0.6007
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tablet, film coatedoral200 mg/1
Tablet, film coatedoral300 mg/1
Tablet, film coatedoral400 mg/1
Tablet, film coatedoral50 mg/1
Film-coated tabletOral use100 mg
Film-coated tabletOral use200 mg
Film-coated tabletOral use300 mg
Film-coated tabletOral use400 mg
Film-coated tabletOral use50 mg
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
pKa10.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0307 mg/mLALOGPS
logP3.07ALOGPS
logP2.7ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)13.6ChemAxon
pKa (Strongest Basic)3.99ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area76.38 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity87.02 m3·mol-1ChemAxon
Polarizability31.97 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Porter RJ, Nohria V, Rundfeldt C: Retigabine. Neurotherapeutics. 2007 Jan;4(1):149-54. [PubMed:17199031 ]
  2. Hermann R, Ferron GM, Erb K, Knebel N, Ruus P, Paul J, Richards L, Cnota HP, Troy S: Effects of age and sex on the disposition of retigabine. Clin Pharmacol Ther. 2003 Jan;73(1):61-70. [PubMed:12545144 ]
  3. Hermann R, Knebel NG, Niebch G, Richards L, Borlak J, Locher M: Pharmacokinetic interaction between retigabine and lamotrigine in healthy subjects. Eur J Clin Pharmacol. 2003 Apr;58(12):795-802. Epub 2003 Feb 28. [PubMed:12698305 ]
  4. Dost R, Rostock A, Rundfeldt C: The anti-hyperalgesic activity of retigabine is mediated by KCNQ potassium channel activation. Naunyn Schmiedebergs Arch Pharmacol. 2004 Apr;369(4):382-90. Epub 2004 Mar 9. [PubMed:15007538 ]
  5. Mikkelsen JD: The KCNQ channel activator retigabine blocks haloperidol-induced c-Fos expression in the striatum of the rat. Neurosci Lett. 2004 May 27;362(3):240-3. [PubMed:15158023 ]
  6. Punke MA, Friederich P: Retigabine stimulates human KCNQ2/Q3 channels in the presence of bupivacaine. Anesthesiology. 2004 Aug;101(2):430-8. [PubMed:15277926 ]
  7. Wuttke TV, Seebohm G, Bail S, Maljevic S, Lerche H: The new anticonvulsant retigabine favors voltage-dependent opening of the Kv7.2 (KCNQ2) channel by binding to its activation gate. Mol Pharmacol. 2005 Apr;67(4):1009-17. Epub 2005 Jan 20. [PubMed:15662042 ]
  8. Fatope MO: Retigabine (ASTA Medica). IDrugs. 2001 Jan;4(1):93-8. [PubMed:16034707 ]
  9. Orhan G, Wuttke TV, Nies AT, Schwab M, Lerche H: Retigabine/Ezogabine, a KCNQ/K(V)7 channel opener: pharmacological and clinical data. Expert Opin Pharmacother. 2012 Aug;13(12):1807-16. doi: 10.1517/14656566.2012.706278. Epub 2012 Jul 12. [PubMed:22783830 ]
  10. Amabile CM, Vasudevan A: Ezogabine: a novel antiepileptic for adjunctive treatment of partial-onset seizures. Pharmacotherapy. 2013 Feb;33(2):187-94. doi: 10.1002/phar.1185. [PubMed:23386597 ]
External Links
ATC CodesN03AX21
AHFS Codes
  • 28:12.92
PDB EntriesNot Available
FDA labelDownload (516 KB)
MSDSDownload (132 KB)
Interactions
Drug Interactions
Drug
7-NitroindazoleThe risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Ezogabine.
AcepromazineThe risk or severity of adverse effects can be increased when Acepromazine is combined with Ezogabine.
AceprometazineThe risk or severity of adverse effects can be increased when Aceprometazine is combined with Ezogabine.
adipiplonThe risk or severity of adverse effects can be increased when adipiplon is combined with Ezogabine.
AgomelatineThe risk or severity of adverse effects can be increased when Agomelatine is combined with Ezogabine.
AlfaxaloneThe risk or severity of adverse effects can be increased when Alfaxalone is combined with Ezogabine.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Ezogabine.
AlphacetylmethadolThe risk or severity of adverse effects can be increased when Alphacetylmethadol is combined with Ezogabine.
AlprazolamThe risk or severity of adverse effects can be increased when Alprazolam is combined with Ezogabine.
AmiodaroneEzogabine may increase the QTc-prolonging activities of Amiodarone.
AmisulprideThe risk or severity of adverse effects can be increased when Amisulpride is combined with Ezogabine.
AmitriptylineThe risk or severity of adverse effects can be increased when Amitriptyline is combined with Ezogabine.
AmobarbitalThe risk or severity of adverse effects can be increased when Amobarbital is combined with Ezogabine.
AmoxapineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Amoxapine.
AmperozideThe risk or severity of adverse effects can be increased when Amperozide is combined with Ezogabine.
AnagrelideEzogabine may increase the QTc-prolonging activities of Anagrelide.
AripiprazoleThe risk or severity of adverse effects can be increased when Aripiprazole is combined with Ezogabine.
Arsenic trioxideEzogabine may increase the QTc-prolonging activities of Arsenic trioxide.
ArtemetherEzogabine may increase the QTc-prolonging activities of Artemether.
ArtesunateThe serum concentration of the active metabolites of Artesunate can be reduced when Artesunate is used in combination with Ezogabine resulting in a loss in efficacy.
ArticaineThe risk or severity of adverse effects can be increased when Articaine is combined with Ezogabine.
AsenapineThe risk or severity of adverse effects can be increased when Asenapine is combined with Ezogabine.
AzaperoneThe risk or severity of adverse effects can be increased when Azaperone is combined with Ezogabine.
AzelastineEzogabine may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
AzelastineThe risk or severity of adverse effects can be increased when Azelastine is combined with Ezogabine.
AzithromycinEzogabine may increase the QTc-prolonging activities of Azithromycin.
BaclofenThe risk or severity of adverse effects can be increased when Baclofen is combined with Ezogabine.
BarbitalThe risk or severity of adverse effects can be increased when Barbital is combined with Ezogabine.
BedaquilineEzogabine may increase the QTc-prolonging activities of Bedaquiline.
BenzocaineThe risk or severity of adverse effects can be increased when Benzocaine is combined with Ezogabine.
Benzyl alcoholThe risk or severity of adverse effects can be increased when Benzyl alcohol is combined with Ezogabine.
BrexpiprazoleThe risk or severity of adverse effects can be increased when Ezogabine is combined with Brexpiprazole.
BrimonidineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
BrimonidineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Brimonidine.
BromazepamThe risk or severity of adverse effects can be increased when Bromazepam is combined with Ezogabine.
BrompheniramineThe risk or severity of adverse effects can be increased when Brompheniramine is combined with Ezogabine.
BrotizolamThe risk or severity of adverse effects can be increased when Brotizolam is combined with Ezogabine.
BupivacaineThe risk or severity of adverse effects can be increased when Bupivacaine is combined with Ezogabine.
BuprenorphineThe risk or severity of adverse effects can be increased when Buprenorphine is combined with Ezogabine.
BuspironeThe risk or severity of adverse effects can be increased when Buspirone is combined with Ezogabine.
ButabarbitalThe risk or severity of adverse effects can be increased when Butabarbital is combined with Ezogabine.
ButacaineThe risk or severity of adverse effects can be increased when Butacaine is combined with Ezogabine.
ButalbitalThe risk or severity of adverse effects can be increased when Butalbital is combined with Ezogabine.
ButambenThe risk or severity of adverse effects can be increased when Butamben is combined with Ezogabine.
ButethalThe risk or severity of adverse effects can be increased when Butethal is combined with Ezogabine.
ButorphanolThe risk or severity of adverse effects can be increased when Butorphanol is combined with Ezogabine.
CarbamazepineThe risk or severity of adverse effects can be increased when Carbamazepine is combined with Ezogabine.
CarbinoxamineThe risk or severity of adverse effects can be increased when Carbinoxamine is combined with Ezogabine.
CarfentanilThe risk or severity of adverse effects can be increased when Carfentanil is combined with Ezogabine.
CarisoprodolThe risk or severity of adverse effects can be increased when Carisoprodol is combined with Ezogabine.
CeritinibEzogabine may increase the QTc-prolonging activities of Ceritinib.
CetirizineThe risk or severity of adverse effects can be increased when Cetirizine is combined with Ezogabine.
Chloral hydrateThe risk or severity of adverse effects can be increased when Chloral hydrate is combined with Ezogabine.
ChlordiazepoxideThe risk or severity of adverse effects can be increased when Chlordiazepoxide is combined with Ezogabine.
ChlormezanoneThe risk or severity of adverse effects can be increased when Chlormezanone is combined with Ezogabine.
ChloroprocaineThe risk or severity of adverse effects can be increased when Chloroprocaine is combined with Ezogabine.
ChloroquineEzogabine may increase the QTc-prolonging activities of Chloroquine.
ChlorphenamineThe risk or severity of adverse effects can be increased when Chlorphenamine is combined with Ezogabine.
ChlorpromazineEzogabine may increase the QTc-prolonging activities of Chlorpromazine.
ChlorpromazineThe risk or severity of adverse effects can be increased when Chlorpromazine is combined with Ezogabine.
ChlorprothixeneThe risk or severity of adverse effects can be increased when Chlorprothixene is combined with Ezogabine.
ChlorzoxazoneThe risk or severity of adverse effects can be increased when Chlorzoxazone is combined with Ezogabine.
CinchocaineThe risk or severity of adverse effects can be increased when Cinchocaine is combined with Ezogabine.
CiprofloxacinEzogabine may increase the QTc-prolonging activities of Ciprofloxacin.
CisaprideEzogabine may increase the QTc-prolonging activities of Cisapride.
CitalopramThe risk or severity of adverse effects can be increased when Ezogabine is combined with Citalopram.
ClarithromycinEzogabine may increase the QTc-prolonging activities of Clarithromycin.
ClemastineThe risk or severity of adverse effects can be increased when Clemastine is combined with Ezogabine.
ClidiniumThe risk or severity of adverse effects can be increased when Clidinium is combined with Ezogabine.
ClobazamThe risk or severity of adverse effects can be increased when Clobazam is combined with Ezogabine.
clomethiazoleThe risk or severity of adverse effects can be increased when clomethiazole is combined with Ezogabine.
ClomipramineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Clomipramine.
ClonazepamThe risk or severity of adverse effects can be increased when Clonazepam is combined with Ezogabine.
ClonidineThe risk or severity of adverse effects can be increased when Clonidine is combined with Ezogabine.
ClorazepateThe risk or severity of adverse effects can be increased when Clorazepate is combined with Ezogabine.
ClozapineEzogabine may increase the QTc-prolonging activities of Clozapine.
ClozapineThe risk or severity of adverse effects can be increased when Clozapine is combined with Ezogabine.
CocaineThe risk or severity of adverse effects can be increased when Cocaine is combined with Ezogabine.
CodeineThe risk or severity of adverse effects can be increased when Codeine is combined with Ezogabine.
CrizotinibEzogabine may increase the QTc-prolonging activities of Crizotinib.
CyclizineThe risk or severity of adverse effects can be increased when Cyclizine is combined with Ezogabine.
CyclobenzaprineThe risk or severity of adverse effects can be increased when Cyclobenzaprine is combined with Ezogabine.
CyproheptadineThe risk or severity of adverse effects can be increased when Cyproheptadine is combined with Ezogabine.
DantroleneThe risk or severity of adverse effects can be increased when Dantrolene is combined with Ezogabine.
DapiprazoleThe risk or severity of adverse effects can be increased when Dapiprazole is combined with Ezogabine.
DapoxetineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Dapoxetine.
deramciclaneThe risk or severity of adverse effects can be increased when deramciclane is combined with Ezogabine.
DesfluraneThe risk or severity of adverse effects can be increased when Desflurane is combined with Ezogabine.
DesipramineThe risk or severity of adverse effects can be increased when Desipramine is combined with Ezogabine.
DesloratadineThe risk or severity of adverse effects can be increased when Desloratadine is combined with Ezogabine.
DetomidineThe risk or severity of adverse effects can be increased when Detomidine is combined with Ezogabine.
DexbrompheniramineThe risk or severity of adverse effects can be increased when Dexbrompheniramine is combined with Ezogabine.
DexmedetomidineThe risk or severity of adverse effects can be increased when Dexmedetomidine is combined with Ezogabine.
DextromoramideThe risk or severity of adverse effects can be increased when Dextromoramide is combined with Ezogabine.
DextropropoxypheneThe risk or severity of adverse effects can be increased when Dextropropoxyphene is combined with Ezogabine.
DezocineThe risk or severity of adverse effects can be increased when Dezocine is combined with Ezogabine.
DiazepamThe risk or severity of adverse effects can be increased when Diazepam is combined with Ezogabine.
DifenoxinThe risk or severity of adverse effects can be increased when Difenoxin is combined with Ezogabine.
DihydrocodeineThe risk or severity of adverse effects can be increased when Dihydrocodeine is combined with Ezogabine.
DihydroetorphineThe risk or severity of adverse effects can be increased when Dihydroetorphine is combined with Ezogabine.
DihydromorphineThe risk or severity of adverse effects can be increased when Dihydromorphine is combined with Ezogabine.
DimenhydrinateThe risk or severity of adverse effects can be increased when Dimenhydrinate is combined with Ezogabine.
DiphenhydramineThe risk or severity of adverse effects can be increased when Diphenhydramine is combined with Ezogabine.
DiphenoxylateThe risk or severity of adverse effects can be increased when Diphenoxylate is combined with Ezogabine.
DisopyramideEzogabine may increase the QTc-prolonging activities of Disopyramide.
DofetilideEzogabine may increase the QTc-prolonging activities of Dofetilide.
DolasetronEzogabine may increase the QTc-prolonging activities of Dolasetron.
DomperidoneEzogabine may increase the QTc-prolonging activities of Domperidone.
DoramectinThe risk or severity of adverse effects can be increased when Doramectin is combined with Ezogabine.
DoxepinThe risk or severity of adverse effects can be increased when Doxepin is combined with Ezogabine.
DoxylamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
DoxylamineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Doxylamine.
DPDPEThe risk or severity of adverse effects can be increased when DPDPE is combined with Ezogabine.
DronabinolDronabinol may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
DronedaroneEzogabine may increase the QTc-prolonging activities of Dronedarone.
DroperidolEzogabine may increase the QTc-prolonging activities of Droperidol.
DroperidolThe risk or severity of adverse effects can be increased when Droperidol is combined with Ezogabine.
DrotebanolThe risk or severity of adverse effects can be increased when Drotebanol is combined with Ezogabine.
DyclonineThe risk or severity of adverse effects can be increased when Dyclonine is combined with Ezogabine.
EcgonineThe risk or severity of adverse effects can be increased when Ecgonine is combined with Ezogabine.
ECGONINE METHYL ESTERThe risk or severity of adverse effects can be increased when ECGONINE METHYL ESTER is combined with Ezogabine.
EfavirenzThe risk or severity of adverse effects can be increased when Efavirenz is combined with Ezogabine.
EliglustatEzogabine may increase the QTc-prolonging activities of Eliglustat.
EnfluraneThe risk or severity of adverse effects can be increased when Enflurane is combined with Ezogabine.
EntacaponeThe risk or severity of adverse effects can be increased when Entacapone is combined with Ezogabine.
ErythromycinEzogabine may increase the QTc-prolonging activities of Erythromycin.
EscitalopramThe risk or severity of adverse effects can be increased when Ezogabine is combined with Escitalopram.
EstazolamThe risk or severity of adverse effects can be increased when Estazolam is combined with Ezogabine.
EszopicloneThe risk or severity of adverse effects can be increased when Eszopiclone is combined with Ezogabine.
EthanolEzogabine may increase the central nervous system depressant (CNS depressant) activities of Ethanol.
EthanolThe risk or severity of adverse effects can be increased when Ethanol is combined with Ezogabine.
EthchlorvynolThe risk or severity of adverse effects can be increased when Ethchlorvynol is combined with Ezogabine.
EthosuximideThe risk or severity of adverse effects can be increased when Ethosuximide is combined with Ezogabine.
EthotoinThe risk or severity of adverse effects can be increased when Ethotoin is combined with Ezogabine.
Ethyl carbamateThe risk or severity of adverse effects can be increased when Ethyl carbamate is combined with Ezogabine.
Ethyl loflazepateThe risk or severity of adverse effects can be increased when Ethyl loflazepate is combined with Ezogabine.
EthylmorphineThe risk or severity of adverse effects can be increased when Ethylmorphine is combined with Ezogabine.
EtidocaineThe risk or severity of adverse effects can be increased when Etidocaine is combined with Ezogabine.
EtifoxineThe risk or severity of adverse effects can be increased when Etifoxine is combined with Ezogabine.
EtizolamThe risk or severity of adverse effects can be increased when Etizolam is combined with Ezogabine.
EtomidateThe risk or severity of adverse effects can be increased when Etomidate is combined with Ezogabine.
EtoperidoneThe risk or severity of adverse effects can be increased when Ezogabine is combined with Etoperidone.
EtorphineThe risk or severity of adverse effects can be increased when Etorphine is combined with Ezogabine.
FelbamateThe risk or severity of adverse effects can be increased when Felbamate is combined with Ezogabine.
FencamfamineThe risk or severity of adverse effects can be increased when Fencamfamine is combined with Ezogabine.
FenfluramineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Fenfluramine.
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Ezogabine.
FexofenadineThe risk or severity of adverse effects can be increased when Fexofenadine is combined with Ezogabine.
FlecainideEzogabine may increase the QTc-prolonging activities of Flecainide.
FlibanserinThe risk or severity of adverse effects can be increased when Flibanserin is combined with Ezogabine.
FludiazepamThe risk or severity of adverse effects can be increased when Fludiazepam is combined with Ezogabine.
FlunarizineThe risk or severity of adverse effects can be increased when Flunarizine is combined with Ezogabine.
FlunitrazepamThe risk or severity of adverse effects can be increased when Flunitrazepam is combined with Ezogabine.
FluoxetineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Fluoxetine.
FlupentixolThe risk or severity of adverse effects can be increased when Flupentixol is combined with Ezogabine.
FluphenazineThe risk or severity of adverse effects can be increased when Fluphenazine is combined with Ezogabine.
FlurazepamThe risk or severity of adverse effects can be increased when Flurazepam is combined with Ezogabine.
FluspirileneThe risk or severity of adverse effects can be increased when Fluspirilene is combined with Ezogabine.
Fluticasone PropionateThe risk or severity of adverse effects can be increased when Fluticasone Propionate is combined with Ezogabine.
FluvoxamineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Fluvoxamine.
FosphenytoinThe risk or severity of adverse effects can be increased when Fosphenytoin is combined with Ezogabine.
FospropofolThe risk or severity of adverse effects can be increased when Fospropofol is combined with Ezogabine.
GabapentinThe risk or severity of adverse effects can be increased when Gabapentin is combined with Ezogabine.
gabapentin enacarbilThe risk or severity of adverse effects can be increased when Ezogabine is combined with gabapentin enacarbil.
Gadobenic acidEzogabine may increase the QTc-prolonging activities of Gadobenic acid.
Gamma Hydroxybutyric AcidThe risk or severity of adverse effects can be increased when Gamma Hydroxybutyric Acid is combined with Ezogabine.
GemifloxacinEzogabine may increase the QTc-prolonging activities of Gemifloxacin.
GlutethimideThe risk or severity of adverse effects can be increased when Glutethimide is combined with Ezogabine.
GoserelinEzogabine may increase the QTc-prolonging activities of Goserelin.
GranisetronEzogabine may increase the QTc-prolonging activities of Granisetron.
GuanfacineThe risk or severity of adverse effects can be increased when Guanfacine is combined with Ezogabine.
HalazepamThe risk or severity of adverse effects can be increased when Halazepam is combined with Ezogabine.
HaloperidolEzogabine may increase the QTc-prolonging activities of Haloperidol.
HaloperidolThe risk or severity of adverse effects can be increased when Haloperidol is combined with Ezogabine.
HalothaneThe risk or severity of adverse effects can be increased when Halothane is combined with Ezogabine.
HeroinThe risk or severity of adverse effects can be increased when Heroin is combined with Ezogabine.
HexobarbitalThe risk or severity of adverse effects can be increased when Hexobarbital is combined with Ezogabine.
HydrocodoneThe risk or severity of adverse effects can be increased when Hydrocodone is combined with Ezogabine.
HydromorphoneThe risk or severity of adverse effects can be increased when Hydromorphone is combined with Ezogabine.
HydroxyzineHydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
HydroxyzineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Hydroxyzine.
IbutilideEzogabine may increase the QTc-prolonging activities of Ibutilide.
IloperidoneThe risk or severity of adverse effects can be increased when Iloperidone is combined with Ezogabine.
ImipramineThe risk or severity of adverse effects can be increased when Imipramine is combined with Ezogabine.
IndalpineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Indalpine.
IsofluraneThe risk or severity of adverse effects can be increased when Isoflurane is combined with Ezogabine.
KetamineThe risk or severity of adverse effects can be increased when Ketamine is combined with Ezogabine.
KetazolamThe risk or severity of adverse effects can be increased when Ketazolam is combined with Ezogabine.
KetobemidoneThe risk or severity of adverse effects can be increased when Ketobemidone is combined with Ezogabine.
LamotrigineThe serum concentration of Lamotrigine can be decreased when it is combined with Ezogabine.
LamotrigineThe risk or severity of adverse effects can be increased when Lamotrigine is combined with Ezogabine.
LenvatinibEzogabine may increase the QTc-prolonging activities of Lenvatinib.
LeuprolideEzogabine may increase the QTc-prolonging activities of Leuprolide.
LevetiracetamThe risk or severity of adverse effects can be increased when Levetiracetam is combined with Ezogabine.
LevobupivacaineThe risk or severity of adverse effects can be increased when Levobupivacaine is combined with Ezogabine.
LevocabastineThe risk or severity of adverse effects can be increased when Levocabastine is combined with Ezogabine.
LevocetirizineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Levocetirizine.
LevodopaThe risk or severity of adverse effects can be increased when Levodopa is combined with Ezogabine.
LevofloxacinEzogabine may increase the QTc-prolonging activities of Levofloxacin.
Levomethadyl AcetateThe risk or severity of adverse effects can be increased when Levomethadyl Acetate is combined with Ezogabine.
LevomilnacipranThe risk or severity of adverse effects can be increased when Ezogabine is combined with Levomilnacipran.
LevorphanolThe risk or severity of adverse effects can be increased when Levorphanol is combined with Ezogabine.
LidocaineThe risk or severity of adverse effects can be increased when Lidocaine is combined with Ezogabine.
LithiumThe risk or severity of adverse effects can be increased when Lithium is combined with Ezogabine.
LofentanilThe risk or severity of adverse effects can be increased when Lofentanil is combined with Ezogabine.
LopinavirEzogabine may increase the QTc-prolonging activities of Lopinavir.
LoratadineThe risk or severity of adverse effects can be increased when Loratadine is combined with Ezogabine.
LorazepamThe risk or severity of adverse effects can be increased when Lorazepam is combined with Ezogabine.
LoxapineThe risk or severity of adverse effects can be increased when Loxapine is combined with Ezogabine.
Lu AA21004The risk or severity of adverse effects can be increased when Ezogabine is combined with Lu AA21004.
LumefantrineEzogabine may increase the QTc-prolonging activities of Lumefantrine.
LurasidoneThe risk or severity of adverse effects can be increased when Lurasidone is combined with Ezogabine.
Magnesium SulfateMagnesium Sulfate may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
Magnesium SulfateThe risk or severity of adverse effects can be increased when Ezogabine is combined with Magnesium Sulfate.
MaprotilineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Ezogabine.
MeclizineThe risk or severity of adverse effects can be increased when Meclizine is combined with Ezogabine.
MedetomidineThe risk or severity of adverse effects can be increased when Medetomidine is combined with Ezogabine.
MefloquineThe therapeutic efficacy of Ezogabine can be decreased when used in combination with Mefloquine.
MelatoninThe risk or severity of adverse effects can be increased when Melatonin is combined with Ezogabine.
MelperoneThe risk or severity of adverse effects can be increased when Melperone is combined with Ezogabine.
MepivacaineThe risk or severity of adverse effects can be increased when Mepivacaine is combined with Ezogabine.
MeprobamateThe risk or severity of adverse effects can be increased when Meprobamate is combined with Ezogabine.
MesoridazineThe risk or severity of adverse effects can be increased when Mesoridazine is combined with Ezogabine.
MetaxaloneThe risk or severity of adverse effects can be increased when Metaxalone is combined with Ezogabine.
MethadoneEzogabine may increase the QTc-prolonging activities of Methadone.
MethadoneThe risk or severity of adverse effects can be increased when Methadone is combined with Ezogabine.
Methadyl AcetateThe risk or severity of adverse effects can be increased when Methadyl Acetate is combined with Ezogabine.
MethapyrileneThe risk or severity of adverse effects can be increased when Methapyrilene is combined with Ezogabine.
MethaqualoneThe risk or severity of adverse effects can be increased when Methaqualone is combined with Ezogabine.
MethocarbamolThe risk or severity of adverse effects can be increased when Methocarbamol is combined with Ezogabine.
MethohexitalThe risk or severity of adverse effects can be increased when Methohexital is combined with Ezogabine.
MethotrimeprazineThe risk or severity of adverse effects can be increased when Methotrimeprazine is combined with Ezogabine.
MethoxyfluraneThe risk or severity of adverse effects can be increased when Methoxyflurane is combined with Ezogabine.
MethsuximideThe risk or severity of adverse effects can be increased when Ezogabine is combined with Methsuximide.
MethylphenobarbitalThe risk or severity of adverse effects can be increased when Methylphenobarbital is combined with Ezogabine.
MetyrosineEzogabine may increase the sedative activities of Metyrosine.
MianserinThe therapeutic efficacy of Ezogabine can be decreased when used in combination with Mianserin.
MidazolamThe risk or severity of adverse effects can be increased when Midazolam is combined with Ezogabine.
MifepristoneMifepristone may increase the QTc-prolonging activities of Ezogabine.
MilnacipranThe risk or severity of adverse effects can be increased when Ezogabine is combined with Milnacipran.
MinocyclineMinocycline may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
MirtazapineEzogabine may increase the central nervous system depressant (CNS depressant) activities of Mirtazapine.
MirtazapineThe risk or severity of adverse effects can be increased when Mirtazapine is combined with Ezogabine.
MolindoneThe risk or severity of adverse effects can be increased when Molindone is combined with Ezogabine.
MorphineThe risk or severity of adverse effects can be increased when Morphine is combined with Ezogabine.
MoxifloxacinEzogabine may increase the QTc-prolonging activities of Moxifloxacin.
NabiloneNabilone may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
NabiloneThe risk or severity of adverse effects can be increased when Ezogabine is combined with Nabilone.
NalbuphineThe risk or severity of adverse effects can be increased when Nalbuphine is combined with Ezogabine.
NilotinibEzogabine may increase the QTc-prolonging activities of Nilotinib.
NitrazepamThe risk or severity of adverse effects can be increased when Nitrazepam is combined with Ezogabine.
Nitrous oxideThe risk or severity of adverse effects can be increased when Nitrous oxide is combined with Ezogabine.
NormethadoneThe risk or severity of adverse effects can be increased when Normethadone is combined with Ezogabine.
NortriptylineThe risk or severity of adverse effects can be increased when Nortriptyline is combined with Ezogabine.
OfloxacinEzogabine may increase the QTc-prolonging activities of Ofloxacin.
OlanzapineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Olanzapine.
OlopatadineThe risk or severity of adverse effects can be increased when Olopatadine is combined with Ezogabine.
OndansetronEzogabine may increase the QTc-prolonging activities of Ondansetron.
OndansetronThe risk or severity of adverse effects can be increased when Ondansetron is combined with Ezogabine.
OpiumThe risk or severity of adverse effects can be increased when Opium is combined with Ezogabine.
OrlistatThe serum concentration of Ezogabine can be decreased when it is combined with Orlistat.
OrphenadrineEzogabine may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
OrphenadrineThe risk or severity of adverse effects can be increased when Orphenadrine is combined with Ezogabine.
OsanetantThe risk or severity of adverse effects can be increased when Osanetant is combined with Ezogabine.
OxazepamThe risk or severity of adverse effects can be increased when Oxazepam is combined with Ezogabine.
OxprenololThe risk or severity of adverse effects can be increased when Oxprenolol is combined with Ezogabine.
OxybuprocaineThe risk or severity of adverse effects can be increased when Oxybuprocaine is combined with Ezogabine.
OxycodoneThe risk or severity of adverse effects can be increased when Oxycodone is combined with Ezogabine.
OxymorphoneThe risk or severity of adverse effects can be increased when Oxymorphone is combined with Ezogabine.
PaliperidoneThe risk or severity of adverse effects can be increased when Paliperidone is combined with Ezogabine.
PanobinostatEzogabine may increase the QTc-prolonging activities of Panobinostat.
ParaldehydeEzogabine may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
ParaldehydeThe risk or severity of adverse effects can be increased when Paraldehyde is combined with Ezogabine.
ParoxetineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Paroxetine.
PazopanibEzogabine may increase the QTc-prolonging activities of Pazopanib.
PentamidineEzogabine may increase the QTc-prolonging activities of Pentamidine.
PentazocineThe risk or severity of adverse effects can be increased when Pentazocine is combined with Ezogabine.
PentobarbitalThe risk or severity of adverse effects can be increased when Pentobarbital is combined with Ezogabine.
PerampanelThe risk or severity of adverse effects can be increased when Ezogabine is combined with Perampanel.
PerflutrenEzogabine may increase the QTc-prolonging activities of Perflutren.
PerospironeThe risk or severity of adverse effects can be increased when Perospirone is combined with Ezogabine.
PerphenazineThe risk or severity of adverse effects can be increased when Perphenazine is combined with Ezogabine.
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Ezogabine.
PhenobarbitalThe risk or severity of adverse effects can be increased when Phenobarbital is combined with Ezogabine.
PhenoxyethanolThe risk or severity of adverse effects can be increased when Phenoxyethanol is combined with Ezogabine.
PhenytoinThe risk or severity of adverse effects can be increased when Phenytoin is combined with Ezogabine.
PimozideThe risk or severity of adverse effects can be increased when Pimozide is combined with Ezogabine.
PipamperoneThe risk or severity of adverse effects can be increased when Pipamperone is combined with Ezogabine.
PipotiazineThe risk or severity of adverse effects can be increased when Pipotiazine is combined with Ezogabine.
PizotifenThe risk or severity of adverse effects can be increased when Ezogabine is combined with Pizotifen.
PomalidomideThe risk or severity of adverse effects can be increased when Ezogabine is combined with Pomalidomide.
PramipexoleEzogabine may increase the sedative activities of Pramipexole.
PramocaineThe risk or severity of adverse effects can be increased when Pramocaine is combined with Ezogabine.
PrazepamThe risk or severity of adverse effects can be increased when Prazepam is combined with Ezogabine.
PregabalinThe risk or severity of adverse effects can be increased when Pregabalin is combined with Ezogabine.
PrilocaineThe risk or severity of adverse effects can be increased when Prilocaine is combined with Ezogabine.
PrimaquineEzogabine may increase the QTc-prolonging activities of Primaquine.
PrimidoneThe risk or severity of adverse effects can be increased when Primidone is combined with Ezogabine.
ProcainamideEzogabine may increase the QTc-prolonging activities of Procainamide.
ProcaineThe risk or severity of adverse effects can be increased when Procaine is combined with Ezogabine.
ProchlorperazineThe risk or severity of adverse effects can be increased when Prochlorperazine is combined with Ezogabine.
PromazineEzogabine may increase the QTc-prolonging activities of Promazine.
PromazineThe risk or severity of adverse effects can be increased when Promazine is combined with Ezogabine.
PromethazineThe risk or severity of adverse effects can be increased when Promethazine is combined with Ezogabine.
PropafenoneEzogabine may increase the QTc-prolonging activities of Propafenone.
ProparacaineThe risk or severity of adverse effects can be increased when Proparacaine is combined with Ezogabine.
PropofolThe risk or severity of adverse effects can be increased when Propofol is combined with Ezogabine.
PropoxycaineThe risk or severity of adverse effects can be increased when Propoxycaine is combined with Ezogabine.
ProtriptylineThe risk or severity of adverse effects can be increased when Protriptyline is combined with Ezogabine.
PSD502The risk or severity of adverse effects can be increased when PSD502 is combined with Ezogabine.
QuazepamThe risk or severity of adverse effects can be increased when Quazepam is combined with Ezogabine.
QuetiapineThe risk or severity of adverse effects can be increased when Quetiapine is combined with Ezogabine.
QuinidineEzogabine may increase the QTc-prolonging activities of Quinidine.
QuinineEzogabine may increase the QTc-prolonging activities of Quinine.
RamelteonThe risk or severity of adverse effects can be increased when Ramelteon is combined with Ezogabine.
RemifentanilThe risk or severity of adverse effects can be increased when Remifentanil is combined with Ezogabine.
RemoxiprideThe risk or severity of adverse effects can be increased when Remoxipride is combined with Ezogabine.
ReserpineThe risk or severity of adverse effects can be increased when Reserpine is combined with Ezogabine.
RisperidoneThe risk or severity of adverse effects can be increased when Risperidone is combined with Ezogabine.
RomifidineThe risk or severity of adverse effects can be increased when Romifidine is combined with Ezogabine.
RopiniroleEzogabine may increase the sedative activities of Ropinirole.
RopivacaineThe risk or severity of adverse effects can be increased when Ropivacaine is combined with Ezogabine.
RotigotineEzogabine may increase the sedative activities of Rotigotine.
RufinamideThe risk or severity of adverse effects can be increased when Rufinamide is combined with Ezogabine.
S-EthylisothioureaThe risk or severity of adverse effects can be increased when S-Ethylisothiourea is combined with Ezogabine.
SaquinavirEzogabine may increase the QTc-prolonging activities of Saquinavir.
ScopolamineThe risk or severity of adverse effects can be increased when Scopolamine is combined with Ezogabine.
SecobarbitalThe risk or severity of adverse effects can be increased when Secobarbital is combined with Ezogabine.
SertindoleThe risk or severity of adverse effects can be increased when Sertindole is combined with Ezogabine.
SertralineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Sertraline.
SevofluraneThe risk or severity of adverse effects can be increased when Sevoflurane is combined with Ezogabine.
Sodium oxybateThe risk or severity of adverse effects can be increased when Sodium oxybate is combined with Ezogabine.
SotalolEzogabine may increase the QTc-prolonging activities of Sotalol.
StiripentolThe risk or severity of adverse effects can be increased when Ezogabine is combined with Stiripentol.
SufentanilThe risk or severity of adverse effects can be increased when Sufentanil is combined with Ezogabine.
SulfisoxazoleEzogabine may increase the QTc-prolonging activities of Sulfisoxazole.
SulpirideThe risk or severity of adverse effects can be increased when Sulpiride is combined with Ezogabine.
SuvorexantThe risk or severity of adverse effects can be increased when Ezogabine is combined with Suvorexant.
TapentadolThe risk or severity of adverse effects can be increased when Ezogabine is combined with Tapentadol.
TasimelteonThe risk or severity of adverse effects can be increased when Ezogabine is combined with Tasimelteon.
TelavancinEzogabine may increase the QTc-prolonging activities of Telavancin.
TelithromycinEzogabine may increase the QTc-prolonging activities of Telithromycin.
TemazepamThe risk or severity of adverse effects can be increased when Temazepam is combined with Ezogabine.
TetrabenazineThe risk or severity of adverse effects can be increased when Tetrabenazine is combined with Ezogabine.
TetracaineThe risk or severity of adverse effects can be increased when Tetracaine is combined with Ezogabine.
TetrodotoxinThe risk or severity of adverse effects can be increased when Tetrodotoxin is combined with Ezogabine.
ThalidomideEzogabine may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
ThalidomideThe risk or severity of adverse effects can be increased when Thalidomide is combined with Ezogabine.
ThiamylalThe risk or severity of adverse effects can be increased when Thiamylal is combined with Ezogabine.
ThiopentalThe risk or severity of adverse effects can be increased when Thiopental is combined with Ezogabine.
ThioridazineThe risk or severity of adverse effects can be increased when Thioridazine is combined with Ezogabine.
ThiothixeneThe risk or severity of adverse effects can be increased when Thiothixene is combined with Ezogabine.
TiagabineThe risk or severity of adverse effects can be increased when Tiagabine is combined with Ezogabine.
TiletamineThe risk or severity of adverse effects can be increased when Tiletamine is combined with Ezogabine.
TizanidineThe risk or severity of adverse effects can be increased when Tizanidine is combined with Ezogabine.
TolcaponeThe risk or severity of adverse effects can be increased when Tolcapone is combined with Ezogabine.
TopiramateThe risk or severity of adverse effects can be increased when Topiramate is combined with Ezogabine.
ToremifeneEzogabine may increase the QTc-prolonging activities of Toremifene.
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Ezogabine.
Trans-2-PhenylcyclopropylamineThe risk or severity of adverse effects can be increased when Trans-2-Phenylcyclopropylamine is combined with Ezogabine.
TranylcypromineThe risk or severity of adverse effects can be increased when Tranylcypromine is combined with Ezogabine.
TrazodoneThe risk or severity of adverse effects can be increased when Ezogabine is combined with Trazodone.
TriazolamThe risk or severity of adverse effects can be increased when Triazolam is combined with Ezogabine.
TrifluoperazineThe risk or severity of adverse effects can be increased when Trifluoperazine is combined with Ezogabine.
TriflupromazineThe risk or severity of adverse effects can be increased when Triflupromazine is combined with Ezogabine.
TrimipramineThe risk or severity of adverse effects can be increased when Trimipramine is combined with Ezogabine.
TriprolidineThe risk or severity of adverse effects can be increased when Triprolidine is combined with Ezogabine.
Valproic AcidThe risk or severity of adverse effects can be increased when Valproic Acid is combined with Ezogabine.
VandetanibEzogabine may increase the QTc-prolonging activities of Vandetanib.
VemurafenibEzogabine may increase the QTc-prolonging activities of Vemurafenib.
VigabatrinThe risk or severity of adverse effects can be increased when Vigabatrin is combined with Ezogabine.
VilazodoneThe risk or severity of adverse effects can be increased when Ezogabine is combined with Vilazodone.
VortioxetineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Vortioxetine.
XylazineThe risk or severity of adverse effects can be increased when Xylazine is combined with Ezogabine.
ZaleplonThe risk or severity of adverse effects can be increased when Zaleplon is combined with Ezogabine.
ZiconotideThe risk or severity of adverse effects can be increased when Ezogabine is combined with Ziconotide.
ZimelidineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Zimelidine.
ZiprasidoneThe risk or severity of adverse effects can be increased when Ziprasidone is combined with Ezogabine.
ZolazepamThe risk or severity of adverse effects can be increased when Zolazepam is combined with Ezogabine.
ZolpidemThe risk or severity of adverse effects can be increased when Zolpidem is combined with Ezogabine.
ZonisamideThe risk or severity of adverse effects can be increased when Zonisamide is combined with Ezogabine.
ZopicloneThe risk or severity of adverse effects can be increased when Zopiclone is combined with Ezogabine.
ZotepineThe risk or severity of adverse effects can be increased when Zotepine is combined with Ezogabine.
ZuclopenthixolThe risk or severity of adverse effects can be increased when Zuclopenthixol is combined with Ezogabine.
Food Interactions
  • With a high-fat meal, Cmax is moderately increased.

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Voltage-gated potassium channel activity
Specific Function:
Probably important in the regulation of neuronal excitability. Associates with KCNQ3 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic in...
Gene Name:
KCNQ2
Uniprot ID:
O43526
Molecular Weight:
95846.575 Da
References
  1. Wuttke TV, Seebohm G, Bail S, Maljevic S, Lerche H: The new anticonvulsant retigabine favors voltage-dependent opening of the Kv7.2 (KCNQ2) channel by binding to its activation gate. Mol Pharmacol. 2005 Apr;67(4):1009-17. Epub 2005 Jan 20. [PubMed:15662042 ]
  2. Hirano K, Kuratani K, Fujiyoshi M, Tashiro N, Hayashi E, Kinoshita M: Kv7.2-7.5 voltage-gated potassium channel (KCNQ2-5) opener, retigabine, reduces capsaicin-induced visceral pain in mice. Neurosci Lett. 2007 Feb 14;413(2):159-62. Epub 2006 Dec 20. [PubMed:17184917 ]
  3. Punke MA, Friederich P: Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels. Anesth Analg. 2007 May;104(5):1256-64, tables of contents. [PubMed:17456683 ]
  4. Main MJ, Cryan JE, Dupere JR, Cox B, Clare JJ, Burbidge SA: Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine. Mol Pharmacol. 2000 Aug;58(2):253-62. [PubMed:10908292 ]
  5. Wickenden AD, Yu W, Zou A, Jegla T, Wagoner PK: Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels. Mol Pharmacol. 2000 Sep;58(3):591-600. [PubMed:10953053 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Voltage-gated potassium channel activity
Specific Function:
Probably important in the regulation of neuronal excitability. Associates with KCNQ2 or KCNQ5 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to sy...
Gene Name:
KCNQ3
Uniprot ID:
O43525
Molecular Weight:
96741.515 Da
References
  1. Hirano K, Kuratani K, Fujiyoshi M, Tashiro N, Hayashi E, Kinoshita M: Kv7.2-7.5 voltage-gated potassium channel (KCNQ2-5) opener, retigabine, reduces capsaicin-induced visceral pain in mice. Neurosci Lett. 2007 Feb 14;413(2):159-62. Epub 2006 Dec 20. [PubMed:17184917 ]
  2. Punke MA, Friederich P: Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels. Anesth Analg. 2007 May;104(5):1256-64, tables of contents. [PubMed:17456683 ]
  3. Main MJ, Cryan JE, Dupere JR, Cox B, Clare JJ, Burbidge SA: Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine. Mol Pharmacol. 2000 Aug;58(2):253-62. [PubMed:10908292 ]
  4. Wickenden AD, Yu W, Zou A, Jegla T, Wagoner PK: Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels. Mol Pharmacol. 2000 Sep;58(3):591-600. [PubMed:10953053 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Potassium channel activity
Specific Function:
Probably important in the regulation of neuronal excitability. May underlie a potassium current involved in regulating the excitability of sensory cells of the cochlea. KCNQ4 channels are blocked by linopirdin, XE991 and bepridil, whereas clofilium is without significant effect. Muscarinic agonist oxotremorine-M strongly suppress KCNQ4 current in CHO cells in which cloned KCNQ4 channels were co...
Gene Name:
KCNQ4
Uniprot ID:
P56696
Molecular Weight:
77099.99 Da
References
  1. Hirano K, Kuratani K, Fujiyoshi M, Tashiro N, Hayashi E, Kinoshita M: Kv7.2-7.5 voltage-gated potassium channel (KCNQ2-5) opener, retigabine, reduces capsaicin-induced visceral pain in mice. Neurosci Lett. 2007 Feb 14;413(2):159-62. Epub 2006 Dec 20. [PubMed:17184917 ]
  2. Schroder RL, Jespersen T, Christophersen P, Strobaek D, Jensen BS, Olesen SP: KCNQ4 channel activation by BMS-204352 and retigabine. Neuropharmacology. 2001 Jun;40(7):888-98. [PubMed:11378159 ]
  3. Borlak J, Gasparic A, Locher M, Schupke H, Hermann R: N-Glucuronidation of the antiepileptic drug retigabine: results from studies with human volunteers, heterologously expressed human UGTs, human liver, kidney, and liver microsomal membranes of Crigler-Najjar type II. Metabolism. 2006 Jun;55(6):711-21. [PubMed:16713428 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Voltage-gated potassium channel activity
Specific Function:
Probably important in the regulation of neuronal excitability. Associates with KCNQ3 to form a potassium channel which contributes to M-type current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons. May contribute, with other potassium channels, to the molecular diversity of a heterogeneous...
Gene Name:
KCNQ5
Uniprot ID:
Q9NR82
Molecular Weight:
102178.015 Da
References
  1. Hirano K, Kuratani K, Fujiyoshi M, Tashiro N, Hayashi E, Kinoshita M: Kv7.2-7.5 voltage-gated potassium channel (KCNQ2-5) opener, retigabine, reduces capsaicin-induced visceral pain in mice. Neurosci Lett. 2007 Feb 14;413(2):159-62. Epub 2006 Dec 20. [PubMed:17184917 ]
  2. Hermann R, Ferron GM, Erb K, Knebel N, Ruus P, Paul J, Richards L, Cnota HP, Troy S: Effects of age and sex on the disposition of retigabine. Clin Pharmacol Ther. 2003 Jan;73(1):61-70. [PubMed:12545144 ]
  3. Borlak J, Gasparic A, Locher M, Schupke H, Hermann R: N-Glucuronidation of the antiepileptic drug retigabine: results from studies with human volunteers, heterologously expressed human UGTs, human liver, kidney, and liver microsomal membranes of Crigler-Najjar type II. Metabolism. 2006 Jun;55(6):711-21. [PubMed:16713428 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid binding
Specific Function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naph...
Gene Name:
UGT1A1
Uniprot ID:
P22309
Molecular Weight:
59590.91 Da
References
  1. Hiller A, Nguyen N, Strassburg CP, Li Q, Jainta H, Pechstein B, Ruus P, Engel J, Tukey RH, Kronbach T: Retigabine N-glucuronidation and its potential role in enterohepatic circulation. Drug Metab Dispos. 1999 May;27(5):605-12. [PubMed:10220490 ]
  2. Borlak J, Gasparic A, Locher M, Schupke H, Hermann R: N-Glucuronidation of the antiepileptic drug retigabine: results from studies with human volunteers, heterologously expressed human UGTs, human liver, kidney, and liver microsomal membranes of Crigler-Najjar type II. Metabolism. 2006 Jun;55(6):711-21. [PubMed:16713428 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Retinoic acid binding
Specific Function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1.
Gene Name:
UGT1A3
Uniprot ID:
P35503
Molecular Weight:
60337.835 Da
References
  1. Hiller A, Nguyen N, Strassburg CP, Li Q, Jainta H, Pechstein B, Ruus P, Engel J, Tukey RH, Kronbach T: Retigabine N-glucuronidation and its potential role in enterohepatic circulation. Drug Metab Dispos. 1999 May;27(5):605-12. [PubMed:10220490 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Protein homodimerization activity
Specific Function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1 (By similarity).
Gene Name:
UGT1A4
Uniprot ID:
P22310
Molecular Weight:
60024.535 Da
References
  1. Hiller A, Nguyen N, Strassburg CP, Li Q, Jainta H, Pechstein B, Ruus P, Engel J, Tukey RH, Kronbach T: Retigabine N-glucuronidation and its potential role in enterohepatic circulation. Drug Metab Dispos. 1999 May;27(5):605-12. [PubMed:10220490 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Retinoic acid binding
Specific Function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1.
Gene Name:
UGT1A9
Uniprot ID:
O60656
Molecular Weight:
59940.495 Da
References
  1. Hiller A, Nguyen N, Strassburg CP, Li Q, Jainta H, Pechstein B, Ruus P, Engel J, Tukey RH, Kronbach T: Retigabine N-glucuronidation and its potential role in enterohepatic circulation. Drug Metab Dispos. 1999 May;27(5):605-12. [PubMed:10220490 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity.
Gene Name:
CYP2A6
Uniprot ID:
P11509
Molecular Weight:
56501.005 Da
References
  1. Orhan G, Wuttke TV, Nies AT, Schwab M, Lerche H: Retigabine/Ezogabine, a KCNQ/K(V)7 channel opener: pharmacological and clinical data. Expert Opin Pharmacother. 2012 Aug;13(12):1807-16. doi: 10.1517/14656566.2012.706278. Epub 2012 Jul 12. [PubMed:22783830 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Arylamine n-acetyltransferase activity
Specific Function:
Participates in the detoxification of a plethora of hydrazine and arylamine drugs. Catalyzes the N- or O-acetylation of various arylamine and heterocyclic amine substrates and is able to bioactivate several known carcinogens.
Gene Name:
NAT2
Uniprot ID:
P11245
Molecular Weight:
33542.235 Da
References
  1. Amabile CM, Vasudevan A: Ezogabine: a novel antiepileptic for adjunctive treatment of partial-onset seizures. Pharmacotherapy. 2013 Feb;33(2):187-94. doi: 10.1002/phar.1185. [PubMed:23386597 ]
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Drug created on October 21, 2007 16:23 / Updated on August 17, 2016 12:24