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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 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
PotigaTablet, film coated50 mg/1OralGlaxo Smith Kline Llc2012-04-19Not applicableUs
TrobaltTablet, film coated300 mgOralGlaxo Group Limited  2011-03-28Not applicableEu
TrobaltTablet, film coated50 mgOralGlaxo Group Limited  2011-03-28Not applicableEu
TrobaltTablet, film coated200 mgOralGlaxo Group Limited  2011-03-28Not applicableEu
TrobaltTablet, film coated400 mgOralGlaxo Group Limited  2011-03-28Not applicableEu
TrobaltTablet, film coated50 mgOralGlaxo Group Limited  2011-03-28Not applicableEu
TrobaltTablet, film coated200 mgOralGlaxo Group Limited  2011-03-28Not applicableEu
TrobaltTablet, film coated400 mgOralGlaxo Group Limited  2011-03-28Not applicableEu
TrobaltTablet, film coated100 mgOralGlaxo Group Limited  2011-03-28Not applicableEu
TrobaltTablet, film coated300 mgOralGlaxo Group Limited  2011-03-28Not applicableEu
TrobaltTablet, film coated100 mgOralGlaxo 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 KeyPCOBBVZJEWWZFR-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
Pharmacology
IndicationAdjuvant treatment of partial-onset seizures.
Structured Indications
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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Potassium voltage-gated channel subfamily KQT member 2ProteinunknownNot AvailableHumanO43526 details
Potassium voltage-gated channel subfamily KQT member 3ProteinunknownNot AvailableHumanO43525 details
Potassium voltage-gated channel subfamily KQT member 4ProteinunknownNot AvailableHumanP56696 details
Potassium voltage-gated channel subfamily KQT member 5ProteinunknownNot AvailableHumanQ9NR82 details
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
Interactions
Drug Interactions
DrugInteractionDrug group
1,1,1,2 TetrafluoroethaneThe risk or severity of adverse effects can be increased when Ezogabine is combined with 1,1,1,2 Tetrafluoroethane.Investigational
7-NitroindazoleThe risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Ezogabine.Experimental
AcepromazineThe risk or severity of adverse effects can be increased when Acepromazine is combined with Ezogabine.Approved, Vet Approved
AceprometazineThe risk or severity of adverse effects can be increased when Aceprometazine is combined with Ezogabine.Approved
adipiplonThe risk or severity of adverse effects can be increased when adipiplon is combined with Ezogabine.Investigational
AgomelatineThe risk or severity of adverse effects can be increased when Agomelatine is combined with Ezogabine.Approved, Investigational
AlfaxaloneThe risk or severity of adverse effects can be increased when Alfaxalone is combined with Ezogabine.Vet Approved
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Ezogabine.Approved, Illicit
AlphacetylmethadolThe risk or severity of adverse effects can be increased when Alphacetylmethadol is combined with Ezogabine.Experimental, Illicit
AlprazolamThe risk or severity of adverse effects can be increased when Alprazolam is combined with Ezogabine.Approved, Illicit, Investigational
AmiodaroneEzogabine may increase the QTc-prolonging activities of Amiodarone.Approved, Investigational
AmisulprideThe risk or severity of adverse effects can be increased when Amisulpride is combined with Ezogabine.Approved, Investigational
AmitriptylineThe risk or severity of adverse effects can be increased when Amitriptyline is combined with Ezogabine.Approved
AmobarbitalThe risk or severity of adverse effects can be increased when Amobarbital is combined with Ezogabine.Approved, Illicit
AmoxapineThe risk or severity of adverse effects can be increased when Amoxapine is combined with Ezogabine.Approved
AmperozideThe risk or severity of adverse effects can be increased when Amperozide is combined with Ezogabine.Experimental
AnagrelideEzogabine may increase the QTc-prolonging activities of Anagrelide.Approved
AripiprazoleThe risk or severity of adverse effects can be increased when Aripiprazole is combined with Ezogabine.Approved, Investigational
Arsenic trioxideEzogabine may increase the QTc-prolonging activities of Arsenic trioxide.Approved, Investigational
ArtemetherEzogabine may increase the QTc-prolonging activities of Artemether.Approved
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.Approved
ArticaineThe risk or severity of adverse effects can be increased when Articaine is combined with Ezogabine.Approved
AsenapineEzogabine may increase the QTc-prolonging activities of Asenapine.Approved
AzaperoneThe risk or severity of adverse effects can be increased when Azaperone is combined with Ezogabine.Vet Approved
AzelastineEzogabine may increase the central nervous system depressant (CNS depressant) activities of Azelastine.Approved
AzelastineThe risk or severity of adverse effects can be increased when Azelastine is combined with Ezogabine.Approved
AzithromycinEzogabine may increase the QTc-prolonging activities of Azithromycin.Approved
BaclofenThe risk or severity of adverse effects can be increased when Baclofen is combined with Ezogabine.Approved
BarbitalThe risk or severity of adverse effects can be increased when Barbital is combined with Ezogabine.Illicit
BedaquilineEzogabine may increase the QTc-prolonging activities of Bedaquiline.Approved
BenperidolThe risk or severity of adverse effects can be increased when Ezogabine is combined with Benperidol.Investigational
BenzocaineThe risk or severity of adverse effects can be increased when Benzocaine is combined with Ezogabine.Approved
Benzyl alcoholThe risk or severity of adverse effects can be increased when Benzyl alcohol is combined with Ezogabine.Approved
BrexpiprazoleThe risk or severity of adverse effects can be increased when Ezogabine is combined with Brexpiprazole.Approved
BrimonidineThe risk or severity of adverse effects can be increased when Brimonidine is combined with Ezogabine.Approved
BrimonidineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.Approved
BromazepamThe risk or severity of adverse effects can be increased when Bromazepam is combined with Ezogabine.Approved, Illicit
BrompheniramineThe risk or severity of adverse effects can be increased when Brompheniramine is combined with Ezogabine.Approved
BrotizolamThe risk or severity of adverse effects can be increased when Brotizolam is combined with Ezogabine.Approved, Withdrawn
BupivacaineThe risk or severity of adverse effects can be increased when Bupivacaine is combined with Ezogabine.Approved, Investigational
BuprenorphineEzogabine may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.Approved, Illicit, Investigational, Vet Approved
BuspironeThe risk or severity of adverse effects can be increased when Buspirone is combined with Ezogabine.Approved, Investigational
ButabarbitalThe risk or severity of adverse effects can be increased when Butabarbital is combined with Ezogabine.Approved, Illicit
ButacaineThe risk or severity of adverse effects can be increased when Butacaine is combined with Ezogabine.Vet Approved
ButalbitalThe risk or severity of adverse effects can be increased when Butalbital is combined with Ezogabine.Approved, Illicit
ButambenThe risk or severity of adverse effects can be increased when Butamben is combined with Ezogabine.Approved
ButethalThe risk or severity of adverse effects can be increased when Butethal is combined with Ezogabine.Approved, Illicit
ButorphanolThe risk or severity of adverse effects can be increased when Butorphanol is combined with Ezogabine.Approved, Illicit, Vet Approved
CarbamazepineThe serum concentration of Ezogabine can be decreased when it is combined with Carbamazepine.Approved, Investigational
CarbinoxamineThe risk or severity of adverse effects can be increased when Carbinoxamine is combined with Ezogabine.Approved
CarfentanilThe risk or severity of adverse effects can be increased when Carfentanil is combined with Ezogabine.Illicit, Vet Approved
CarisoprodolThe risk or severity of adverse effects can be increased when Carisoprodol is combined with Ezogabine.Approved
CeritinibEzogabine may increase the QTc-prolonging activities of Ceritinib.Approved
CetirizineThe risk or severity of adverse effects can be increased when Cetirizine is combined with Ezogabine.Approved
Chloral hydrateThe risk or severity of adverse effects can be increased when Chloral hydrate is combined with Ezogabine.Approved, Illicit, Vet Approved
ChlordiazepoxideThe risk or severity of adverse effects can be increased when Chlordiazepoxide is combined with Ezogabine.Approved, Illicit
ChlormezanoneThe risk or severity of adverse effects can be increased when Chlormezanone is combined with Ezogabine.Approved, Withdrawn
ChloroprocaineThe risk or severity of adverse effects can be increased when Chloroprocaine is combined with Ezogabine.Approved
ChloroquineEzogabine may increase the QTc-prolonging activities of Chloroquine.Approved, Vet Approved
ChlorphenamineThe risk or severity of adverse effects can be increased when Chlorphenamine is combined with Ezogabine.Approved
ChlorpromazineEzogabine may increase the QTc-prolonging activities of Chlorpromazine.Approved, Vet Approved
ChlorprothixeneThe risk or severity of adverse effects can be increased when Chlorprothixene is combined with Ezogabine.Approved, Withdrawn
ChlorzoxazoneThe risk or severity of adverse effects can be increased when Chlorzoxazone is combined with Ezogabine.Approved
CinchocaineThe risk or severity of adverse effects can be increased when Cinchocaine is combined with Ezogabine.Approved, Vet Approved
CiprofloxacinEzogabine may increase the QTc-prolonging activities of Ciprofloxacin.Approved, Investigational
CisaprideEzogabine may increase the QTc-prolonging activities of Cisapride.Approved, Investigational, Withdrawn
CitalopramEzogabine may increase the QTc-prolonging activities of Citalopram.Approved
ClarithromycinEzogabine may increase the QTc-prolonging activities of Clarithromycin.Approved
ClemastineThe risk or severity of adverse effects can be increased when Clemastine is combined with Ezogabine.Approved
ClidiniumThe risk or severity of adverse effects can be increased when Clidinium is combined with Ezogabine.Approved
ClobazamThe risk or severity of adverse effects can be increased when Clobazam is combined with Ezogabine.Approved, Illicit
clomethiazoleThe risk or severity of adverse effects can be increased when clomethiazole is combined with Ezogabine.Investigational
ClomipramineThe risk or severity of adverse effects can be increased when Clomipramine is combined with Ezogabine.Approved, Vet Approved
ClonazepamThe risk or severity of adverse effects can be increased when Clonazepam is combined with Ezogabine.Approved, Illicit
ClonidineThe risk or severity of adverse effects can be increased when Clonidine is combined with Ezogabine.Approved
ClorazepateThe risk or severity of adverse effects can be increased when Clorazepate is combined with Ezogabine.Approved, Illicit
ClozapineEzogabine may increase the QTc-prolonging activities of Clozapine.Approved
CocaineThe risk or severity of adverse effects can be increased when Cocaine is combined with Ezogabine.Approved, Illicit
CodeineThe risk or severity of adverse effects can be increased when Codeine is combined with Ezogabine.Approved, Illicit
CrizotinibEzogabine may increase the QTc-prolonging activities of Crizotinib.Approved
CyclizineThe risk or severity of adverse effects can be increased when Cyclizine is combined with Ezogabine.Approved
CyclobenzaprineThe risk or severity of adverse effects can be increased when Cyclobenzaprine is combined with Ezogabine.Approved
CyproheptadineThe risk or severity of adverse effects can be increased when Cyproheptadine is combined with Ezogabine.Approved
DantroleneThe risk or severity of adverse effects can be increased when Dantrolene is combined with Ezogabine.Approved
DapiprazoleThe risk or severity of adverse effects can be increased when Dapiprazole is combined with Ezogabine.Approved
DapoxetineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Dapoxetine.Investigational
deramciclaneThe risk or severity of adverse effects can be increased when deramciclane is combined with Ezogabine.Investigational
DesfluraneThe risk or severity of adverse effects can be increased when Desflurane is combined with Ezogabine.Approved
DesipramineThe risk or severity of adverse effects can be increased when Desipramine is combined with Ezogabine.Approved
DesloratadineThe risk or severity of adverse effects can be increased when Desloratadine is combined with Ezogabine.Approved, Investigational
DesvenlafaxineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Desvenlafaxine.Approved
DetomidineThe risk or severity of adverse effects can be increased when Detomidine is combined with Ezogabine.Vet Approved
DexbrompheniramineThe risk or severity of adverse effects can be increased when Dexbrompheniramine is combined with Ezogabine.Approved
DexmedetomidineThe risk or severity of adverse effects can be increased when Dexmedetomidine is combined with Ezogabine.Approved, Vet Approved
DextromoramideThe risk or severity of adverse effects can be increased when Dextromoramide is combined with Ezogabine.Experimental, Illicit
DextropropoxypheneThe risk or severity of adverse effects can be increased when Dextropropoxyphene is combined with Ezogabine.Approved, Illicit, Withdrawn
DezocineThe risk or severity of adverse effects can be increased when Dezocine is combined with Ezogabine.Approved
DiazepamThe risk or severity of adverse effects can be increased when Diazepam is combined with Ezogabine.Approved, Illicit, Vet Approved
DifenoxinThe risk or severity of adverse effects can be increased when Difenoxin is combined with Ezogabine.Approved, Illicit
DihydrocodeineThe risk or severity of adverse effects can be increased when Dihydrocodeine is combined with Ezogabine.Approved, Illicit
DihydroetorphineThe risk or severity of adverse effects can be increased when Dihydroetorphine is combined with Ezogabine.Experimental, Illicit
DihydromorphineThe risk or severity of adverse effects can be increased when Dihydromorphine is combined with Ezogabine.Experimental, Illicit
DimenhydrinateThe risk or severity of adverse effects can be increased when Dimenhydrinate is combined with Ezogabine.Approved
DiphenhydramineThe risk or severity of adverse effects can be increased when Diphenhydramine is combined with Ezogabine.Approved
DiphenoxylateThe risk or severity of adverse effects can be increased when Diphenoxylate is combined with Ezogabine.Approved, Illicit
DisopyramideEzogabine may increase the QTc-prolonging activities of Disopyramide.Approved
DofetilideEzogabine may increase the QTc-prolonging activities of Dofetilide.Approved
DolasetronEzogabine may increase the QTc-prolonging activities of Dolasetron.Approved
DomperidoneEzogabine may increase the QTc-prolonging activities of Domperidone.Approved, Investigational, Vet Approved
DoramectinThe risk or severity of adverse effects can be increased when Doramectin is combined with Ezogabine.Vet Approved
DoxepinThe risk or severity of adverse effects can be increased when Doxepin is combined with Ezogabine.Approved
DoxylamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.Approved, Vet Approved
DPDPEThe risk or severity of adverse effects can be increased when DPDPE is combined with Ezogabine.Investigational
DronabinolDronabinol may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.Approved, Illicit
DronedaroneEzogabine may increase the QTc-prolonging activities of Dronedarone.Approved
DroperidolDroperidol may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.Approved, Vet Approved
DrotebanolThe risk or severity of adverse effects can be increased when Drotebanol is combined with Ezogabine.Experimental, Illicit
DuloxetineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Duloxetine.Approved
DyclonineThe risk or severity of adverse effects can be increased when Dyclonine is combined with Ezogabine.Approved
EcgonineThe risk or severity of adverse effects can be increased when Ecgonine is combined with Ezogabine.Experimental, Illicit
ECGONINE METHYL ESTERThe risk or severity of adverse effects can be increased when ECGONINE METHYL ESTER is combined with Ezogabine.Experimental
EcopipamThe risk or severity of adverse effects can be increased when Ezogabine is combined with Ecopipam.Investigational
EfavirenzThe risk or severity of adverse effects can be increased when Efavirenz is combined with Ezogabine.Approved, Investigational
EliglustatEzogabine may increase the QTc-prolonging activities of Eliglustat.Approved
EnfluraneThe risk or severity of adverse effects can be increased when Enflurane is combined with Ezogabine.Approved, Vet Approved
EntacaponeThe risk or severity of adverse effects can be increased when Entacapone is combined with Ezogabine.Approved, Investigational
ErythromycinEzogabine may increase the QTc-prolonging activities of Erythromycin.Approved, Vet Approved
EscitalopramEzogabine may increase the QTc-prolonging activities of Escitalopram.Approved, Investigational
EstazolamThe risk or severity of adverse effects can be increased when Estazolam is combined with Ezogabine.Approved, Illicit
EszopicloneThe risk or severity of adverse effects can be increased when Eszopiclone is combined with Ezogabine.Approved
EthanolThe risk or severity of adverse effects can be increased when Ethanol is combined with Ezogabine.Approved
EthchlorvynolThe risk or severity of adverse effects can be increased when Ethchlorvynol is combined with Ezogabine.Approved, Illicit, Withdrawn
EthosuximideThe risk or severity of adverse effects can be increased when Ethosuximide is combined with Ezogabine.Approved
EthotoinThe risk or severity of adverse effects can be increased when Ethotoin is combined with Ezogabine.Approved
Ethyl carbamateThe risk or severity of adverse effects can be increased when Ethyl carbamate is combined with Ezogabine.Withdrawn
Ethyl loflazepateThe risk or severity of adverse effects can be increased when Ethyl loflazepate is combined with Ezogabine.Approved, Illicit
EthylmorphineThe risk or severity of adverse effects can be increased when Ethylmorphine is combined with Ezogabine.Approved, Illicit
EtidocaineThe risk or severity of adverse effects can be increased when Etidocaine is combined with Ezogabine.Approved
EtifoxineThe risk or severity of adverse effects can be increased when Etifoxine is combined with Ezogabine.Withdrawn
EtizolamThe risk or severity of adverse effects can be increased when Etizolam is combined with Ezogabine.Approved
EtomidateThe risk or severity of adverse effects can be increased when Etomidate is combined with Ezogabine.Approved
EtoperidoneThe risk or severity of adverse effects can be increased when Ezogabine is combined with Etoperidone.Approved
EtorphineThe risk or severity of adverse effects can be increased when Etorphine is combined with Ezogabine.Illicit, Vet Approved
FelbamateThe risk or severity of adverse effects can be increased when Felbamate is combined with Ezogabine.Approved
FencamfamineThe risk or severity of adverse effects can be increased when Fencamfamine is combined with Ezogabine.Approved, Illicit, Withdrawn
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Ezogabine.Approved, Illicit, Investigational, Vet Approved
FexofenadineThe risk or severity of adverse effects can be increased when Fexofenadine is combined with Ezogabine.Approved
FlecainideEzogabine may increase the QTc-prolonging activities of Flecainide.Approved, Withdrawn
FlibanserinThe risk or severity of adverse effects can be increased when Flibanserin is combined with Ezogabine.Approved
FludiazepamThe risk or severity of adverse effects can be increased when Fludiazepam is combined with Ezogabine.Approved, Illicit
FlunarizineThe risk or severity of adverse effects can be increased when Flunarizine is combined with Ezogabine.Approved
FlunitrazepamThe risk or severity of adverse effects can be increased when Flunitrazepam is combined with Ezogabine.Approved, Illicit
FluoxetineEzogabine may increase the QTc-prolonging activities of Fluoxetine.Approved, Vet Approved
FlupentixolEzogabine may increase the QTc-prolonging activities of Flupentixol.Approved, Withdrawn
FluphenazineThe risk or severity of adverse effects can be increased when Fluphenazine is combined with Ezogabine.Approved
FlurazepamThe risk or severity of adverse effects can be increased when Flurazepam is combined with Ezogabine.Approved, Illicit
FluspirileneThe risk or severity of adverse effects can be increased when Fluspirilene is combined with Ezogabine.Approved
Fluticasone PropionateThe risk or severity of adverse effects can be increased when Fluticasone Propionate is combined with Ezogabine.Approved
FluvoxamineThe risk or severity of adverse effects can be increased when Fluvoxamine is combined with Ezogabine.Approved, Investigational
FosphenytoinThe serum concentration of Ezogabine can be decreased when it is combined with Fosphenytoin.Approved
FospropofolThe risk or severity of adverse effects can be increased when Fospropofol is combined with Ezogabine.Approved, Illicit
GabapentinThe risk or severity of adverse effects can be increased when Gabapentin is combined with Ezogabine.Approved, Investigational
gabapentin enacarbilThe risk or severity of adverse effects can be increased when Ezogabine is combined with gabapentin enacarbil.Approved
Gadobenic acidEzogabine may increase the QTc-prolonging activities of Gadobenic acid.Approved
Gamma Hydroxybutyric AcidThe risk or severity of adverse effects can be increased when Gamma Hydroxybutyric Acid is combined with Ezogabine.Approved, Illicit
GemifloxacinEzogabine may increase the QTc-prolonging activities of Gemifloxacin.Approved, Investigational
GepironeThe risk or severity of adverse effects can be increased when Ezogabine is combined with Gepirone.Investigational
GlutethimideThe risk or severity of adverse effects can be increased when Glutethimide is combined with Ezogabine.Approved, Illicit
GoserelinEzogabine may increase the QTc-prolonging activities of Goserelin.Approved
GranisetronEzogabine may increase the QTc-prolonging activities of Granisetron.Approved, Investigational
GuanfacineThe risk or severity of adverse effects can be increased when Guanfacine is combined with Ezogabine.Approved, Investigational
HalazepamThe risk or severity of adverse effects can be increased when Halazepam is combined with Ezogabine.Approved, Illicit, Withdrawn
HaloperidolEzogabine may increase the QTc-prolonging activities of Haloperidol.Approved
HalothaneThe risk or severity of adverse effects can be increased when Halothane is combined with Ezogabine.Approved, Vet Approved
HeroinThe risk or severity of adverse effects can be increased when Heroin is combined with Ezogabine.Approved, Illicit
HexobarbitalThe risk or severity of adverse effects can be increased when Hexobarbital is combined with Ezogabine.Approved
HydrocodoneEzogabine may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.Approved, Illicit
HydromorphoneThe risk or severity of adverse effects can be increased when Hydromorphone is combined with Ezogabine.Approved, Illicit
HydroxyzineHydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.Approved
IbutilideEzogabine may increase the QTc-prolonging activities of Ibutilide.Approved
IloperidoneEzogabine may increase the QTc-prolonging activities of Iloperidone.Approved
ImipramineThe risk or severity of adverse effects can be increased when Imipramine is combined with Ezogabine.Approved
IndalpineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Indalpine.Investigational, Withdrawn
IsofluraneThe risk or severity of adverse effects can be increased when Isoflurane is combined with Ezogabine.Approved, Vet Approved
KetamineThe risk or severity of adverse effects can be increased when Ketamine is combined with Ezogabine.Approved, Vet Approved
KetazolamThe risk or severity of adverse effects can be increased when Ketazolam is combined with Ezogabine.Approved
KetobemidoneThe risk or severity of adverse effects can be increased when Ketobemidone is combined with Ezogabine.Approved
LamotrigineThe serum concentration of Lamotrigine can be decreased when it is combined with Ezogabine.Approved, Investigational
LenvatinibEzogabine may increase the QTc-prolonging activities of Lenvatinib.Approved
LeuprolideEzogabine may increase the QTc-prolonging activities of Leuprolide.Approved, Investigational
LevetiracetamThe risk or severity of adverse effects can be increased when Levetiracetam is combined with Ezogabine.Approved, Investigational
LevobupivacaineThe risk or severity of adverse effects can be increased when Levobupivacaine is combined with Ezogabine.Approved
LevocabastineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Levocabastine.Approved
LevocetirizineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Levocetirizine.Approved
LevodopaThe risk or severity of adverse effects can be increased when Levodopa is combined with Ezogabine.Approved
LevofloxacinEzogabine may increase the QTc-prolonging activities of Levofloxacin.Approved, Investigational
Levomethadyl AcetateThe risk or severity of adverse effects can be increased when Levomethadyl Acetate is combined with Ezogabine.Approved
LevomilnacipranThe risk or severity of adverse effects can be increased when Ezogabine is combined with Levomilnacipran.Approved
LevorphanolThe risk or severity of adverse effects can be increased when Levorphanol is combined with Ezogabine.Approved
LidocaineThe risk or severity of adverse effects can be increased when Lidocaine is combined with Ezogabine.Approved, Vet Approved
LithiumThe risk or severity of adverse effects can be increased when Lithium is combined with Ezogabine.Approved
LofentanilThe risk or severity of adverse effects can be increased when Lofentanil is combined with Ezogabine.Illicit
LopinavirEzogabine may increase the QTc-prolonging activities of Lopinavir.Approved
LoratadineThe risk or severity of adverse effects can be increased when Loratadine is combined with Ezogabine.Approved
LorazepamThe risk or severity of adverse effects can be increased when Lorazepam is combined with Ezogabine.Approved
LoxapineThe risk or severity of adverse effects can be increased when Loxapine is combined with Ezogabine.Approved
Lu AA21004The risk or severity of adverse effects can be increased when Lu AA21004 is combined with Ezogabine.Investigational
LumefantrineEzogabine may increase the QTc-prolonging activities of Lumefantrine.Approved
LurasidoneThe risk or severity of adverse effects can be increased when Lurasidone is combined with Ezogabine.Approved
Magnesium SulfateMagnesium Sulfate may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.Approved, Vet Approved
MaprotilineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Ezogabine.Approved
MeclizineThe risk or severity of adverse effects can be increased when Meclizine is combined with Ezogabine.Approved
MedetomidineThe risk or severity of adverse effects can be increased when Medetomidine is combined with Ezogabine.Vet Approved
MefloquineThe therapeutic efficacy of Ezogabine can be decreased when used in combination with Mefloquine.Approved
MelatoninThe risk or severity of adverse effects can be increased when Melatonin is combined with Ezogabine.Approved, Nutraceutical, Vet Approved
MelperoneThe risk or severity of adverse effects can be increased when Melperone is combined with Ezogabine.Approved
MepivacaineThe risk or severity of adverse effects can be increased when Mepivacaine is combined with Ezogabine.Approved, Vet Approved
MeprobamateThe risk or severity of adverse effects can be increased when Meprobamate is combined with Ezogabine.Approved, Illicit
MesoridazineThe risk or severity of adverse effects can be increased when Mesoridazine is combined with Ezogabine.Approved
MetaxaloneThe risk or severity of adverse effects can be increased when Metaxalone is combined with Ezogabine.Approved
MethadoneEzogabine may increase the QTc-prolonging activities of Methadone.Approved
Methadyl AcetateThe risk or severity of adverse effects can be increased when Methadyl Acetate is combined with Ezogabine.Approved, Illicit
MethapyrileneThe risk or severity of adverse effects can be increased when Methapyrilene is combined with Ezogabine.Withdrawn
MethaqualoneThe risk or severity of adverse effects can be increased when Methaqualone is combined with Ezogabine.Illicit, Withdrawn
MethocarbamolThe risk or severity of adverse effects can be increased when Methocarbamol is combined with Ezogabine.Approved, Vet Approved
MethohexitalThe risk or severity of adverse effects can be increased when Methohexital is combined with Ezogabine.Approved
MethotrimeprazineEzogabine may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.Approved
MethoxyfluraneThe risk or severity of adverse effects can be increased when Methoxyflurane is combined with Ezogabine.Approved, Vet Approved
MethsuximideThe risk or severity of adverse effects can be increased when Ezogabine is combined with Methsuximide.Approved
MethylphenobarbitalThe risk or severity of adverse effects can be increased when Methylphenobarbital is combined with Ezogabine.Approved
MetyrosineEzogabine may increase the sedative activities of Metyrosine.Approved
MianserinThe therapeutic efficacy of Ezogabine can be decreased when used in combination with Mianserin.Approved
MidazolamThe risk or severity of adverse effects can be increased when Midazolam is combined with Ezogabine.Approved, Illicit
MifepristoneMifepristone may increase the QTc-prolonging activities of Ezogabine.Approved, Investigational
MilnacipranThe risk or severity of adverse effects can be increased when Ezogabine is combined with Milnacipran.Approved
MinocyclineMinocycline may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.Approved, Investigational
MirtazapineEzogabine may increase the central nervous system depressant (CNS depressant) activities of Mirtazapine.Approved
MolindoneThe risk or severity of adverse effects can be increased when Molindone is combined with Ezogabine.Approved
MorphineThe risk or severity of adverse effects can be increased when Morphine is combined with Ezogabine.Approved, Investigational
MoxifloxacinEzogabine may increase the QTc-prolonging activities of Moxifloxacin.Approved, Investigational
NabiloneNabilone may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.Approved, Investigational
NalbuphineThe risk or severity of adverse effects can be increased when Nalbuphine is combined with Ezogabine.Approved
NefazodoneThe risk or severity of adverse effects can be increased when Ezogabine is combined with Nefazodone.Approved, Withdrawn
NilotinibEzogabine may increase the QTc-prolonging activities of Nilotinib.Approved, Investigational
NitrazepamThe risk or severity of adverse effects can be increased when Nitrazepam is combined with Ezogabine.Approved
Nitrous oxideThe risk or severity of adverse effects can be increased when Nitrous oxide is combined with Ezogabine.Approved, Vet Approved
NormethadoneThe risk or severity of adverse effects can be increased when Normethadone is combined with Ezogabine.Approved, Illicit
NortriptylineThe risk or severity of adverse effects can be increased when Nortriptyline is combined with Ezogabine.Approved
OfloxacinEzogabine may increase the QTc-prolonging activities of Ofloxacin.Approved
OlanzapineThe risk or severity of adverse effects can be increased when Olanzapine is combined with Ezogabine.Approved, Investigational
OlopatadineThe risk or severity of adverse effects can be increased when Olopatadine is combined with Ezogabine.Approved
OndansetronEzogabine may increase the QTc-prolonging activities of Ondansetron.Approved
OpiumThe risk or severity of adverse effects can be increased when Opium is combined with Ezogabine.Approved, Illicit
OrlistatThe serum concentration of Ezogabine can be decreased when it is combined with Orlistat.Approved, Investigational
OrphenadrineEzogabine may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.Approved
OsanetantThe risk or severity of adverse effects can be increased when Osanetant is combined with Ezogabine.Investigational
OxazepamThe risk or severity of adverse effects can be increased when Oxazepam is combined with Ezogabine.Approved
OxetacaineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Oxetacaine.Investigational
OxprenololThe risk or severity of adverse effects can be increased when Oxprenolol is combined with Ezogabine.Approved
OxybuprocaineThe risk or severity of adverse effects can be increased when Oxybuprocaine is combined with Ezogabine.Approved
OxycodoneThe risk or severity of adverse effects can be increased when Oxycodone is combined with Ezogabine.Approved, Illicit, Investigational
OxymorphoneThe risk or severity of adverse effects can be increased when Oxymorphone is combined with Ezogabine.Approved, Investigational, Vet Approved
PaliperidoneEzogabine may increase the QTc-prolonging activities of Paliperidone.Approved
PanobinostatEzogabine may increase the QTc-prolonging activities of Panobinostat.Approved, Investigational
ParaldehydeEzogabine may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.Approved
ParoxetineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Paroxetine.Approved, Investigational
PazopanibEzogabine may increase the QTc-prolonging activities of Pazopanib.Approved
PentamidineEzogabine may increase the QTc-prolonging activities of Pentamidine.Approved
PentazocineThe risk or severity of adverse effects can be increased when Pentazocine is combined with Ezogabine.Approved, Vet Approved
PentobarbitalThe risk or severity of adverse effects can be increased when Pentobarbital is combined with Ezogabine.Approved, Vet Approved
PerampanelPerampanel may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.Approved
PerazineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Perazine.Investigational
PerflutrenEzogabine may increase the QTc-prolonging activities of Perflutren.Approved
PerospironeThe risk or severity of adverse effects can be increased when Perospirone is combined with Ezogabine.Approved
PerphenazineThe risk or severity of adverse effects can be increased when Perphenazine is combined with Ezogabine.Approved
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Ezogabine.Approved
PhenobarbitalThe risk or severity of adverse effects can be increased when Phenobarbital is combined with Ezogabine.Approved
PhenoxyethanolThe risk or severity of adverse effects can be increased when Phenoxyethanol is combined with Ezogabine.Approved
PhenytoinThe serum concentration of Ezogabine can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PimozideEzogabine may increase the QTc-prolonging activities of Pimozide.Approved
PipamperoneThe risk or severity of adverse effects can be increased when Pipamperone is combined with Ezogabine.Approved
PipotiazineThe risk or severity of adverse effects can be increased when Pipotiazine is combined with Ezogabine.Approved
PiritramideThe risk or severity of adverse effects can be increased when Ezogabine is combined with Piritramide.Investigational
PizotifenThe risk or severity of adverse effects can be increased when Ezogabine is combined with Pizotifen.Approved
PomalidomideThe risk or severity of adverse effects can be increased when Ezogabine is combined with Pomalidomide.Approved
PramipexoleEzogabine may increase the sedative activities of Pramipexole.Approved, Investigational
PramocaineThe risk or severity of adverse effects can be increased when Pramocaine is combined with Ezogabine.Approved
PrazepamThe risk or severity of adverse effects can be increased when Prazepam is combined with Ezogabine.Approved, Illicit
PregabalinThe risk or severity of adverse effects can be increased when Pregabalin is combined with Ezogabine.Approved, Illicit, Investigational
PregnanoloneThe risk or severity of adverse effects can be increased when Ezogabine is combined with Pregnanolone.Investigational
PrilocaineThe risk or severity of adverse effects can be increased when Prilocaine is combined with Ezogabine.Approved
PrimaquineEzogabine may increase the QTc-prolonging activities of Primaquine.Approved
PrimidoneThe risk or severity of adverse effects can be increased when Primidone is combined with Ezogabine.Approved, Vet Approved
ProcainamideEzogabine may increase the QTc-prolonging activities of Procainamide.Approved
ProcaineThe risk or severity of adverse effects can be increased when Procaine is combined with Ezogabine.Approved, Investigational, Vet Approved
ProchlorperazineThe risk or severity of adverse effects can be increased when Prochlorperazine is combined with Ezogabine.Approved, Vet Approved
PromazineEzogabine may increase the QTc-prolonging activities of Promazine.Approved, Vet Approved
PromethazineThe risk or severity of adverse effects can be increased when Promethazine is combined with Ezogabine.Approved
PropafenoneEzogabine may increase the QTc-prolonging activities of Propafenone.Approved
ProparacaineThe risk or severity of adverse effects can be increased when Proparacaine is combined with Ezogabine.Approved, Vet Approved
PropofolThe risk or severity of adverse effects can be increased when Propofol is combined with Ezogabine.Approved, Investigational, Vet Approved
PropoxycaineThe risk or severity of adverse effects can be increased when Propoxycaine is combined with Ezogabine.Approved
ProtriptylineThe risk or severity of adverse effects can be increased when Protriptyline is combined with Ezogabine.Approved
PSD502The risk or severity of adverse effects can be increased when PSD502 is combined with Ezogabine.Investigational
QuazepamThe risk or severity of adverse effects can be increased when Quazepam is combined with Ezogabine.Approved, Illicit
QuetiapineEzogabine may increase the QTc-prolonging activities of Quetiapine.Approved
QuinidineEzogabine may increase the QTc-prolonging activities of Quinidine.Approved
QuinineEzogabine may increase the QTc-prolonging activities of Quinine.Approved
RacloprideThe risk or severity of adverse effects can be increased when Ezogabine is combined with Raclopride.Investigational
RamelteonThe risk or severity of adverse effects can be increased when Ramelteon is combined with Ezogabine.Approved, Investigational
RemifentanilThe risk or severity of adverse effects can be increased when Remifentanil is combined with Ezogabine.Approved
RemoxiprideThe risk or severity of adverse effects can be increased when Remoxipride is combined with Ezogabine.Approved, Withdrawn
ReserpineThe risk or severity of adverse effects can be increased when Reserpine is combined with Ezogabine.Approved
RisperidoneThe risk or severity of adverse effects can be increased when Risperidone is combined with Ezogabine.Approved, Investigational
RitanserinThe risk or severity of adverse effects can be increased when Ezogabine is combined with Ritanserin.Investigational
RomifidineThe risk or severity of adverse effects can be increased when Romifidine is combined with Ezogabine.Vet Approved
RopiniroleEzogabine may increase the sedative activities of Ropinirole.Approved, Investigational
RopivacaineThe risk or severity of adverse effects can be increased when Ropivacaine is combined with Ezogabine.Approved
RotigotineEzogabine may increase the sedative activities of Rotigotine.Approved
RufinamideThe risk or severity of adverse effects can be increased when Rufinamide is combined with Ezogabine.Approved
S-EthylisothioureaThe risk or severity of adverse effects can be increased when S-Ethylisothiourea is combined with Ezogabine.Experimental
Sage 547The risk or severity of adverse effects can be increased when Ezogabine is combined with Sage 547.Investigational
SaquinavirEzogabine may increase the QTc-prolonging activities of Saquinavir.Approved, Investigational
ScopolamineThe risk or severity of adverse effects can be increased when Scopolamine is combined with Ezogabine.Approved
SecobarbitalThe risk or severity of adverse effects can be increased when Secobarbital is combined with Ezogabine.Approved, Vet Approved
SertindoleThe risk or severity of adverse effects can be increased when Sertindole is combined with Ezogabine.Approved, Withdrawn
SertralineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Sertraline.Approved
SevofluraneThe risk or severity of adverse effects can be increased when Sevoflurane is combined with Ezogabine.Approved, Vet Approved
Sodium oxybateSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.Approved
SotalolEzogabine may increase the QTc-prolonging activities of Sotalol.Approved
StiripentolThe risk or severity of adverse effects can be increased when Ezogabine is combined with Stiripentol.Approved
SufentanilThe risk or severity of adverse effects can be increased when Sufentanil is combined with Ezogabine.Approved, Investigational
SulfisoxazoleEzogabine may increase the QTc-prolonging activities of Sulfisoxazole.Approved, Vet Approved
SulpirideThe risk or severity of adverse effects can be increased when Sulpiride is combined with Ezogabine.Approved
SuvorexantEzogabine may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.Approved
TandospironeThe risk or severity of adverse effects can be increased when Ezogabine is combined with Tandospirone.Investigational
TapentadolTapentadol may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.Approved
TasimelteonThe risk or severity of adverse effects can be increased when Ezogabine is combined with Tasimelteon.Approved
TelavancinEzogabine may increase the QTc-prolonging activities of Telavancin.Approved
TelithromycinEzogabine may increase the QTc-prolonging activities of Telithromycin.Approved
TemazepamThe risk or severity of adverse effects can be increased when Temazepam is combined with Ezogabine.Approved
TetrabenazineEzogabine may increase the QTc-prolonging activities of Tetrabenazine.Approved
TetracaineThe risk or severity of adverse effects can be increased when Tetracaine is combined with Ezogabine.Approved, Vet Approved
TetrodotoxinThe risk or severity of adverse effects can be increased when Tetrodotoxin is combined with Ezogabine.Investigational
ThalidomideEzogabine may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.Approved, Investigational, Withdrawn
ThiamylalThe risk or severity of adverse effects can be increased when Thiamylal is combined with Ezogabine.Approved, Vet Approved
ThiopentalThe risk or severity of adverse effects can be increased when Thiopental is combined with Ezogabine.Approved, Vet Approved
ThioridazineEzogabine may increase the QTc-prolonging activities of Thioridazine.Approved
ThiothixeneThe risk or severity of adverse effects can be increased when Thiothixene is combined with Ezogabine.Approved
TiagabineThe risk or severity of adverse effects can be increased when Tiagabine is combined with Ezogabine.Approved
TiaprideThe risk or severity of adverse effects can be increased when Ezogabine is combined with Tiapride.Investigational
TiletamineThe risk or severity of adverse effects can be increased when Tiletamine is combined with Ezogabine.Vet Approved
TizanidineThe risk or severity of adverse effects can be increased when Tizanidine is combined with Ezogabine.Approved
TolcaponeThe risk or severity of adverse effects can be increased when Tolcapone is combined with Ezogabine.Approved, Withdrawn
TopiramateThe risk or severity of adverse effects can be increased when Topiramate is combined with Ezogabine.Approved
ToremifeneEzogabine may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Ezogabine.Approved, Investigational
Trans-2-PhenylcyclopropylamineThe risk or severity of adverse effects can be increased when Trans-2-Phenylcyclopropylamine is combined with Ezogabine.Experimental
TranylcypromineThe risk or severity of adverse effects can be increased when Tranylcypromine is combined with Ezogabine.Approved
TrazodoneThe risk or severity of adverse effects can be increased when Trazodone is combined with Ezogabine.Approved, Investigational
TriazolamThe risk or severity of adverse effects can be increased when Triazolam is combined with Ezogabine.Approved
TrifluoperazineThe risk or severity of adverse effects can be increased when Trifluoperazine is combined with Ezogabine.Approved
TriflupromazineThe risk or severity of adverse effects can be increased when Triflupromazine is combined with Ezogabine.Approved, Vet Approved
TrimipramineThe risk or severity of adverse effects can be increased when Trimipramine is combined with Ezogabine.Approved
TriprolidineThe risk or severity of adverse effects can be increased when Triprolidine is combined with Ezogabine.Approved
Uc1010The risk or severity of adverse effects can be increased when Ezogabine is combined with Uc1010.Investigational
Valproic AcidThe risk or severity of adverse effects can be increased when Valproic Acid is combined with Ezogabine.Approved, Investigational
VandetanibEzogabine may increase the QTc-prolonging activities of Vandetanib.Approved
VemurafenibEzogabine may increase the QTc-prolonging activities of Vemurafenib.Approved
VenlafaxineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Venlafaxine.Approved
VigabatrinThe risk or severity of adverse effects can be increased when Vigabatrin is combined with Ezogabine.Approved
VortioxetineThe risk or severity of adverse effects can be increased when Vortioxetine is combined with Ezogabine.Approved
XylazineThe risk or severity of adverse effects can be increased when Xylazine is combined with Ezogabine.Vet Approved
ZaleplonThe risk or severity of adverse effects can be increased when Zaleplon is combined with Ezogabine.Approved, Illicit, Investigational
ZiconotideThe risk or severity of adverse effects can be increased when Ezogabine is combined with Ziconotide.Approved
ZimelidineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Zimelidine.Withdrawn
ZiprasidoneEzogabine may increase the QTc-prolonging activities of Ziprasidone.Approved
ZolazepamThe risk or severity of adverse effects can be increased when Zolazepam is combined with Ezogabine.Vet Approved
ZolpidemEzogabine may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.Approved
ZonisamideThe risk or severity of adverse effects can be increased when Zonisamide is combined with Ezogabine.Approved, Investigational
ZopicloneThe risk or severity of adverse effects can be increased when Zopiclone is combined with Ezogabine.Approved
ZotepineThe risk or severity of adverse effects can be increased when Zotepine is combined with Ezogabine.Approved
ZuclopenthixolEzogabine may increase the QTc-prolonging activities of Zuclopenthixol.Approved, Investigational
Food Interactions
  • With a high-fat meal, Cmax is moderately increased.
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)
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
Tablet, film coatedOral100 mg
Tablet, film coatedOral200 mg
Tablet, film coatedOral300 mg
Tablet, film coatedOral400 mg
Tablet, film coatedOral50 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
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

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