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Details

Stereochemistry ACHIRAL
Molecular Formula C16H18FN3O2
Molecular Weight 303.332
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of EZOGABINE

SMILES

CCOC(=Nc1ccc(cc1N)NCc2ccc(cc2)F)O

InChI

InChIKey=PCOBBVZJEWWZFR-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C16H18FN3O2
Molecular Weight 303.332
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/21686305; https://www.ncbi.nlm.nih.gov/pubmed/?term=22221318

Ezogabine (U.S. adopted name) or retigabine (international nonproprietary name) is one of a family of aminopyrroles with anticonvulsant activity. It is used as an adjunctive treatment for partial epilepsies in treatment-experienced adult patients. The drug was approved by the European Medicines Agency under the trade name Trobalt and by the United States Food and Drug Administration (FDA), under the trade name Potiga. The mechanism by which ezogabine exerts its therapeutic effects has not been fully elucidated. In vitro studies indicate that ezogabine enhances transmembrane potassium currents mediated by the KCNQ (Kv7.2 to 7.5) family of ion channels. By activating KCNQ channels, ezogabine is thought to stabilize the resting membrane potential and reduce brain excitability. This mechanism of action is unique among antiepileptic drugs, and may hold promise for the treatment of other neurologic conditions, including migraine, tinnitus and neuropathic pain. In vitro studies suggest that ezogabine may also exert therapeutic effects through augmentation of GABA-mediated currents.

CNS Activity

Curator's Comment:: Ezogabine can cross the blood–brain barrier and is not subject to P-glycoprotein active transport across this barrier, free brain concentrations will closely follow free plasma concentrations.

Originator

Curator's Comment:: # Valeant Pharmaceuticals International and GlaxoSmithKline

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
1.60000000000000009 µM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Secondary
POTIGA

Approved Use

Indicated as adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments and for whom the benefits outweigh the risk of retinal abnormalities and potential decline in visual acuity

Launch Date

1307664000000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
414 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
498 ng/mL
100 mg 2 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
551.9 ng/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: HIGH-FAT
561 ng/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
819 ng/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
842 ng/mL
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
993 ng/mL
250 mg 2 times / day multiple, oral
dose: 250 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
978 ng/mL
200 mg 2 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
728.8 ng/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
938.7 ng/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: HIGH-FAT
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1831 ng × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
1914 ng × h/mL
100 mg 2 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
3972.5 ng × h/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: HIGH-FAT
4393.8 ng × h/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
5134 ng × h/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
5136 ng × h/mL
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
5184 ng × h/mL
250 mg 2 times / day multiple, oral
dose: 250 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
5279 ng × h/mL
200 mg 2 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
7355.9 ng × h/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
7895.9 ng × h/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: HIGH-FAT
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.4 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
7.2 h
100 mg 2 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
7.4 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
7.9 h
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
6.8 h
250 mg 2 times / day multiple, oral
dose: 250 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
7 h
200 mg 2 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
7.57 h
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
6.28 h
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EZOGABINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: HIGH-FAT
Doses

Doses

DosePopulationAdverse events​
350 mg 3 times / day multiple, oral
Recommended
Dose: 350 mg, 3 times / day
Route: oral
Route: multiple
Dose: 350 mg, 3 times / day
Sources:
unhealthy, 30 years
Health Status: unhealthy
Age Group: 30 years
Sex: F
Sources:
Disc. AE: Mucocutaneous disorder...
AEs leading to
discontinuation/dose reduction:
Mucocutaneous disorder (2 patients)
Sources:
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Disc. AE: Dizziness, Confusional state...
Other AEs: Urinary tract infection, Influenza...
AEs leading to
discontinuation/dose reduction:
Dizziness (9.2%)
Confusional state (6.5%)
Ataxia (2.6%)
Somnolence (3.9%)
Dysarthria (2.6%)
Headache (1.3%)
Fatigue (3.3%)
Vision blurred (1.3%)
Tremor (2.6%)
Nausea (2.6%)
Speech disorder (0.7%)
Memory impairment (0.7%)
Diplopia (2%)
Gait disturbance (1.3%)
Balance disorder (0.7%)
Vomiting (1.3%)
Anxiety (1.3%)
Disturbance in attention (2%)
Other AEs:
Urinary tract infection (11.8%)
Influenza (7.8%)
Constipation (5.9%)
Urinary hesitation (5.9%)
Dysuria (5.2%)
Disorientation (5.2%)
Sources:
50 mg 3 times / day multiple, oral
Recommended
Dose: 50 mg, 3 times / day
Route: oral
Route: multiple
Dose: 50 mg, 3 times / day
Sources:
unhealthy, 48 years
Health Status: unhealthy
Age Group: 48 years
Sex: F
Sources:
Disc. AE: Maculopathy...
AEs leading to
discontinuation/dose reduction:
Maculopathy (1 patient)
Sources:
600 mg 1 times / day multiple, oral
Recommended
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
Disc. AE: Dizziness, Confusional state...
AEs leading to
discontinuation/dose reduction:
Dizziness (6%)
Confusional state (4%)
Fatigue (3%)
Somnolence (3%)
Sources:
2500 mg 1 times / day multiple, oral
Overdose
Dose: 2500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2500 mg, 1 times / day
Sources:
unhealthy
Other AEs: Agitation, Aggressive behavior...
Other AEs:
Agitation
Aggressive behavior
Irritability
Sources:
AEs

AEs

AESignificanceDosePopulation
Mucocutaneous disorder 2 patients
Disc. AE
350 mg 3 times / day multiple, oral
Recommended
Dose: 350 mg, 3 times / day
Route: oral
Route: multiple
Dose: 350 mg, 3 times / day
Sources:
unhealthy, 30 years
Health Status: unhealthy
Age Group: 30 years
Sex: F
Sources:
Balance disorder 0.7%
Disc. AE
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Memory impairment 0.7%
Disc. AE
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Speech disorder 0.7%
Disc. AE
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Anxiety 1.3%
Disc. AE
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Gait disturbance 1.3%
Disc. AE
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Headache 1.3%
Disc. AE
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Vision blurred 1.3%
Disc. AE
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Vomiting 1.3%
Disc. AE
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Urinary tract infection 11.8%
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Diplopia 2%
Disc. AE
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Disturbance in attention 2%
Disc. AE
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Ataxia 2.6%
Disc. AE
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Dysarthria 2.6%
Disc. AE
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Nausea 2.6%
Disc. AE
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Tremor 2.6%
Disc. AE
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Fatigue 3.3%
Disc. AE
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Somnolence 3.9%
Disc. AE
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Disorientation 5.2%
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Dysuria 5.2%
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Constipation 5.9%
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Urinary hesitation 5.9%
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Confusional state 6.5%
Disc. AE
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Influenza 7.8%
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Dizziness 9.2%
Disc. AE
1200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, 37.7 years (range: 18 –71 years)
Health Status: unhealthy
Age Group: 37.7 years (range: 18 –71 years)
Sex: M+F
Sources:
Maculopathy 1 patient
Disc. AE
50 mg 3 times / day multiple, oral
Recommended
Dose: 50 mg, 3 times / day
Route: oral
Route: multiple
Dose: 50 mg, 3 times / day
Sources:
unhealthy, 48 years
Health Status: unhealthy
Age Group: 48 years
Sex: F
Sources:
Fatigue 3%
Disc. AE
600 mg 1 times / day multiple, oral
Recommended
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
Somnolence 3%
Disc. AE
600 mg 1 times / day multiple, oral
Recommended
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
Confusional state 4%
Disc. AE
600 mg 1 times / day multiple, oral
Recommended
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
Dizziness 6%
Disc. AE
600 mg 1 times / day multiple, oral
Recommended
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
Aggressive behavior
2500 mg 1 times / day multiple, oral
Overdose
Dose: 2500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2500 mg, 1 times / day
Sources:
unhealthy
Agitation
2500 mg 1 times / day multiple, oral
Overdose
Dose: 2500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2500 mg, 1 times / day
Sources:
unhealthy
Irritability
2500 mg 1 times / day multiple, oral
Overdose
Dose: 2500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2500 mg, 1 times / day
Sources:
unhealthy
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
likely
no
no
no
no
no
no
no
no
no
no
no
no
no
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no evidence
no
no
no
no
no
no
no
yes
yes
yes
yes
no (pharmacogenomic study)
Comment: AUC of the acetylated metabolite was higher in subjects with UGT1A1*28 mutation versus subjects with UGT1A1 wildtype. The differences in PK parameters do not warrant dose change recommendations.
Page: 14
Tox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
Delayed sclerosis, neuroprotection, and limbic epileptogenesis after status epilepticus in the rat.
2002
Effects of the anticonvulsant retigabine on cultured cortical neurons: changes in electroresponsive properties and synaptic transmission.
2002 Apr
Novel anticonvulsant medications in development.
2002 Oct
Progress report on new antiepileptic drugs: a summary of the Sixth Eilat Conference (EILAT VI).
2002 Sep
Pharmacokinetic interaction between retigabine and lamotrigine in healthy subjects.
2003 Apr
A medium-throughput functional assay of KCNQ2 potassium channels using rubidium efflux and atomic absorption spectrometry.
2003 Aug 15
The anticonvulsant retigabine attenuates nociceptive behaviours in rat models of persistent and neuropathic pain.
2003 Jan 24
Synergy between retigabine and GABA in modulating the convulsant site of the GABAA receptor complex.
2003 Mar 19
The anti-hyperalgesic activity of retigabine is mediated by KCNQ potassium channel activation.
2004 Apr
Retigabine stimulates human KCNQ2/Q3 channels in the presence of bupivacaine.
2004 Aug
KCNQ2 is a nodal K+ channel.
2004 Feb 4
M-current modulators alter rat spinal nociceptive transmission: an electrophysiological study in vitro.
2004 Mar
The KCNQ channel activator retigabine blocks haloperidol-induced c-Fos expression in the striatum of the rat.
2004 May 27
Progress report on new antiepileptic drugs: a summary of the Seventh Eilat Conference (EILAT VII).
2004 Sep-Oct
Voltage gated ion channels: targets for anticonvulsant drugs.
2005
The new anticonvulsant retigabine favors voltage-dependent opening of the Kv7.2 (KCNQ2) channel by binding to its activation gate.
2005 Apr
Effects of anticonvulsants on soman-induced epileptiform activity in the guinea-pig in vitro hippocampus.
2005 Aug 22
Effects of M-current modulators on the excitability of immature rat spinal sensory and motor neurones.
2005 Dec
Gateways to clinical trials.
2005 Jan-Feb
Anxiolytic effects of Maxipost (BMS-204352) and retigabine via activation of neuronal Kv7 channels.
2005 Jul
Retigabine: chemical synthesis to clinical application.
2005 Spring
[Voltage-activated potassium channels of the inhibitory interneurons of the hippocampus in culture].
2006
Retigabine: in partial seizures.
2006
Ionic mechanisms of autorhythmic firing in rat cerebellar Golgi cells.
2006 Aug 1
Diverse mechanisms of antiepileptic drugs in the development pipeline.
2006 Jun
KCNQ/Kv7 channel regulation of hippocampal gamma-frequency firing in the absence of synaptic transmission.
2006 May
KCNQ channels mediate IKs, a slow K+ current regulating excitability in the rat node of Ranvier.
2006 May 15
The role of Gilbert's syndrome and frequent NAT2 slow acetylation polymorphisms in the pharmacokinetics of retigabine.
2006 May-Jun
Antidystonic effects of Kv7 (KCNQ) channel openers in the dt sz mutant, an animal model of primary paroxysmal dystonia.
2006 Nov
The acrylamide (S)-1 differentially affects Kv7 (KCNQ) potassium channels.
2006 Nov
An exploratory open trial on safety and efficacy of the anticonvulsant retigabine in acute manic patients.
2006 Oct
Randomized, multicenter, dose-ranging trial of retigabine for partial-onset seizures.
2007 Apr 10
Recruitment of apical dendritic T-type Ca2+ channels by backpropagating spikes underlies de novo intrinsic bursting in hippocampal epileptogenesis.
2007 Apr 15
Inactivation as a new regulatory mechanism for neuronal Kv7 channels.
2007 Apr 15
A tale of switched functions: from cyclooxygenase inhibition to M-channel modulation in new diphenylamine derivatives.
2007 Dec 26
Kv7.2-7.5 voltage-gated potassium channel (KCNQ2-5) opener, retigabine, reduces capsaicin-induced visceral pain in mice.
2007 Feb 14
Retigabine.
2007 Jan
Progress report on new antiepileptic drugs: a summary of the Eigth Eilat Conference (EILAT VIII).
2007 Jan
Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels.
2007 May
Phenytoin- and carbamazepine-resistant spontaneous bursting in rat entorhinal cortex is blocked by retigabine in vitro.
2007 May
The neuronal KCNQ channel opener retigabine inhibits locomotor activity and reduces forebrain excitatory responses to the psychostimulants cocaine, methylphenidate and phencyclidine.
2007 Sep 10
The effectiveness of anticonvulsants in psychiatric disorders.
2008
The mechanisms of neurodegenerative processes and current pharmacotherapy of Alzheimer's disease.
2008 Feb
Expression profile and characterisation of a truncated KCNQ5 splice variant.
2008 Jul 11
Retigabine reduces the excitability of unmyelinated peripheral human axons.
2008 Jun
Gateways to clinical trials.
2008 Mar
Antiepileptogenic and antiictogenic effects of retigabine under conditions of rapid kindling: an ontogenic study.
2008 Oct
Bimodal effects of the Kv7 channel activator retigabine on vascular K+ currents.
2008 Sep
Retigabine, the specific KCNQ channel opener, blocks ectopic discharges in axotomized sensory fibres.
2008 Sep 15
Expression and function of K(v)7 channels in murine myometrium throughout oestrous cycle.
2009 Mar
Patents

Sample Use Guides

Potiga should be given orally in 3 equally divided doses daily, with or without food. The initial dosage should be 100 mg 3 times daily (300 mg per day) and should be increased gradually at weekly intervals by no more than 50 mg 3 times daily (increase in the daily dose of no more than 150 mg per day) up to a maintenance dosage of 200 mg to 400 mg 3 times daily (600 mg to 1,200 mg per day), based on individual patient response and tolerability.
Route of Administration: Oral
KCNQ4 channels, stably expressed in HEK293 cells, were activated by retigabine (ezogabine) in a reversible and concentration-dependent manner in the concentration range 0.1-10 uM. Retigabine shifted the KCNQ4 channel activation curves towards more negative potentials by about 10 mV.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:37:48 UTC 2021
Edited
by admin
on Fri Jun 25 21:37:48 UTC 2021
Record UNII
12G01I6BBU
Record Status Validated (UNII)
Record Version
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Name Type Language
EZOGABINE
DASH   MI   ORANGE BOOK   USAN   VANDF  
USAN  
Official Name English
RETIGABINE
EMA EPAR   INN   MART.   WHO-DD  
INN  
Official Name English
POTIGA
Brand Name English
AWD-21360
Code English
GW582892X
Code English
EZOGABINE [MI]
Common Name English
TROBALT
Brand Name English
GKE-841
Code English
RETIGABINE [WHO-DD]
Common Name English
EZOGABINE [VANDF]
Common Name English
GW-582892X
Code English
RETIGABINE [MART.]
Common Name English
RETIGABINE [INN]
Common Name English
AWD21-360
Code English
CARBAMIC ACID, (2-AMINO-4-(((4-FLUORO-PHENYL)METHYL)AMINO)PHENYL)-ETHYL ESTER
Systematic Name English
RETIGABINE [EMA EPAR]
Common Name English
D-23129
Code English
WAY-143841
Code English
EZOGABINE [ORANGE BOOK]
Common Name English
N-(2-AMINO-4-(4-FLUOROBENZYLAMINO)-PHENYL)CARBAMIC ACID ETHYL ESTER
Systematic Name English
EZOGABINE [USAN]
Common Name English
Classification Tree Code System Code
NDF-RT N0000182729
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
DEA NO. 2779
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
EMA ASSESSMENT REPORTS TROBALT (AUTHORIZED: EPILEPSY)
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
FDA ORPHAN DRUG 639118
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
WHO-VATC QN03AX21
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
NCI_THESAURUS C264
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
WHO-ATC N03AX21
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
LIVERTOX 397
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
Code System Code Type Description
PUBCHEM
121892
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
PRIMARY
MERCK INDEX
M5229
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
PRIMARY Merck Index
HSDB
8171
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
PRIMARY
WIKIPEDIA
Retigabine
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
PRIMARY
IUPHAR
2601
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
PRIMARY
LACTMED
Ezogabine
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
PRIMARY
INN
7545
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
PRIMARY
CAS
150812-12-7
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
PRIMARY
DRUG CENTRAL
4181
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
PRIMARY
NCI_THESAURUS
C72839
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
PRIMARY
EVMPD
SUB10291MIG
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
PRIMARY
RXCUI
1112990
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
PRIMARY RxNorm
NDF-RT
N0000182728
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
PRIMARY Potassium Channel Openers [MoA]
EPA CompTox
150812-12-7
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
PRIMARY
DRUG BANK
DB04953
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
PRIMARY
ChEMBL
CHEMBL41355
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
PRIMARY
FDA UNII
12G01I6BBU
Created by admin on Fri Jun 25 21:37:48 UTC 2021 , Edited by admin on Fri Jun 25 21:37:48 UTC 2021
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
URINE
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC
ORAL BIOAVAILABILITY PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC INTRAVENOUS ADMINISTRATION