Details
Stereochemistry | ACHIRAL |
Molecular Formula | C16H18FN3O2 |
Molecular Weight | 303.3314 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCOC(=O)NC1=CC=C(NCC2=CC=C(F)C=C2)C=C1N
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)
Molecular Formula | C16H18FN3O2 |
Molecular Weight | 303.3314 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionCurator'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
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=22221318
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.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2363063 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=21686305 |
1.6 µM [EC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Secondary | POTIGA Approved UseIndicated 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 Date1.30766406E12 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse 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 n = 2 Health Status: unhealthy Condition: epilepsy Age Group: 30 years Sex: F Population Size: 2 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 Sources: |
Disc. AE: Dizziness, Confusional state... Other AEs: Urinary tract infection, Influenza... AEs leading to discontinuation/dose reduction: Dizziness (9.2%) Other AEs: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%) Urinary tract infection (11.8%) Sources: Influenza (7.8%) Constipation (5.9%) Urinary hesitation (5.9%) Dysuria (5.2%) Disorientation (5.2%) |
50 mg 3 times / day multiple, oral (starting) Recommended Dose: 50 mg, 3 times / day Route: oral Route: multiple Dose: 50 mg, 3 times / day Sources: |
unhealthy, 48 years n = 1 Health Status: unhealthy Condition: epilepsy Age Group: 48 years Sex: F Population Size: 1 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 n = 813 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 813 Sources: |
Disc. AE: Dizziness, Confusional state... AEs leading to discontinuation/dose reduction: Dizziness (6%) Sources: Confusional state (4%) Fatigue (3%) Somnolence (3%) |
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 Health Status: unhealthy Condition: epilepsy Sources: |
Other AEs: Agitation, Aggressive behavior... Other AEs: Agitation Sources: Aggressive behavior Irritability |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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 n = 2 Health Status: unhealthy Condition: epilepsy Age Group: 30 years Sex: F Population Size: 2 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 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) n = 153 Health Status: unhealthy Condition: drug-resistant partial epilepsy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F Population Size: 153 Sources: |
Maculopathy | 1 patient Disc. AE |
50 mg 3 times / day multiple, oral (starting) Recommended Dose: 50 mg, 3 times / day Route: oral Route: multiple Dose: 50 mg, 3 times / day Sources: |
unhealthy, 48 years n = 1 Health Status: unhealthy Condition: epilepsy Age Group: 48 years Sex: F Population Size: 1 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 n = 813 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 813 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 n = 813 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 813 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 n = 813 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 813 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 n = 813 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 813 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 Health Status: unhealthy Condition: epilepsy Sources: |
|
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 Health Status: unhealthy Condition: epilepsy Sources: |
|
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 Health Status: unhealthy Condition: epilepsy Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=149 Page: 149.0 |
likely | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=177 Page: 177.0 |
no | |||
Page: 15.0 |
no | |||
Page: 15.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=177 Page: 177.0 |
no | |||
Page: 15.0 |
no | |||
Page: 15.0 |
no | |||
Page: 15.0 |
no | |||
Page: 15.0 |
no | |||
Page: 15.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=177 Page: 177.0 |
no | |||
Page: 15.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=177 Page: 177.0 |
no | |||
Page: 15.0 |
no |
Drug as victim
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000PharmR.pdf#page=19 Page: 19.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Future prospects for the drug treatment of epilepsy. | 2001 |
|
The new generation of GABA enhancers. Potential in the treatment of epilepsy. | 2001 |
|
Characterization of KCNQ5/Q3 potassium channels expressed in mammalian cells. | 2001 Jan |
|
Progress report on new antiepileptic drugs: a summary of the Fifth Eilat Conference (EILAT V). | 2001 Jan |
|
KCNQ4 channel activation by BMS-204352 and retigabine. | 2001 Jun |
|
Influence of retigabine on the anticonvulsant activity of some antiepileptic drugs against audiogenic seizures in DBA/2 mice. | 2001 Mar |
|
Effects of retigabine on rhythmic synchronous activity of human neocortical slices. | 2001 May |
|
Multiple-dose, linear, dose-proportional pharmacokinetics of retigabine in healthy volunteers. | 2002 Feb |
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Activation of KCNQ5 channels stably expressed in HEK293 cells by BMS-204352. | 2002 Feb 22 |
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Pharmacokinetic interaction between retigabine and lamotrigine in healthy subjects. | 2003 Apr |
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Voltage-independent KCNQ4 currents induced by (+/-)BMS-204352. | 2003 Aug |
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Activation of M1 muscarinic receptors triggers transmitter release from rat sympathetic neurons through an inhibition of M-type K+ channels. | 2003 Dec 15 |
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Protein 4.1N is required for translocation of inositol 1,4,5-trisphosphate receptor type 1 to the basolateral membrane domain in polarized Madin-Darby canine kidney cells. | 2003 Feb 7 |
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Effects of age and sex on the disposition of retigabine. | 2003 Jan |
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Neuroprotective effects of anticonvulsants in rat hippocampal slice cultures exposed to oxygen/glucose deprivation. | 2003 Jan 2 |
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Lack of pharmacokinetic interaction between retigabine and phenobarbitone at steady-state in healthy subjects. | 2003 Jul |
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Effect of the KCNQ potassium channel opener retigabine on single KCNQ2/3 channels expressed in CHO cells. | 2003 May 15 |
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A thallium-sensitive, fluorescence-based assay for detecting and characterizing potassium channel modulators in mammalian cells. | 2004 Dec |
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KCNQ/M channels control spike afterdepolarization and burst generation in hippocampal neurons. | 2004 May 12 |
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Progress report on new antiepileptic drugs: a summary of the Seventh Eilat Conference (EILAT VII). | 2004 Sep-Oct |
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Ion channel defects in idiopathic epilepsies. | 2005 |
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Ion channels and epilepsy. | 2005 |
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Voltage gated ion channels: targets for anticonvulsant drugs. | 2005 |
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The new anticonvulsant retigabine favors voltage-dependent opening of the Kv7.2 (KCNQ2) channel by binding to its activation gate. | 2005 Apr |
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Kv7/KCNQ/M and HCN/h, but not KCa2/SK channels, contribute to the somatic medium after-hyperpolarization and excitability control in CA1 hippocampal pyramidal cells. | 2005 Aug 1 |
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Effects of M-current modulators on the excitability of immature rat spinal sensory and motor neurones. | 2005 Dec |
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Gateways to clinical trials. | 2005 Jan-Feb |
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Anxiolytic effects of Maxipost (BMS-204352) and retigabine via activation of neuronal Kv7 channels. | 2005 Jul |
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Presynaptic inhibition of transmitter release from rat sympathetic neurons by bradykinin. | 2005 Jun |
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The KCNQ5 potassium channel from mouse: a broadly expressed M-current like potassium channel modulated by zinc, pH, and volume changes. | 2005 Sep 13 |
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[Voltage-activated potassium channels of the inhibitory interneurons of the hippocampus in culture]. | 2006 |
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Pulmonary vasoconstrictor action of KCNQ potassium channel blockers. | 2006 Feb 20 |
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New antiepileptic drugs that are second generation to existing antiepileptic drugs. | 2006 Jun |
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Diverse mechanisms of antiepileptic drugs in the development pipeline. | 2006 Jun |
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KCNQ/Kv7 channel regulation of hippocampal gamma-frequency firing in the absence of synaptic transmission. | 2006 May |
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KCNQ channels mediate IKs, a slow K+ current regulating excitability in the rat node of Ranvier. | 2006 May 15 |
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Recruitment of apical dendritic T-type Ca2+ channels by backpropagating spikes underlies de novo intrinsic bursting in hippocampal epileptogenesis. | 2007 Apr 15 |
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Phenytoin- and carbamazepine-resistant spontaneous bursting in rat entorhinal cortex is blocked by retigabine in vitro. | 2007 May |
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Pharmacological comparison of anticonvulsant drugs in animal models of persistent pain and anxiety. | 2007 Oct |
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The effectiveness of anticonvulsants in psychiatric disorders. | 2008 |
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Expression profile and characterisation of a truncated KCNQ5 splice variant. | 2008 Jul 11 |
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Retigabine reduces the excitability of unmyelinated peripheral human axons. | 2008 Jun |
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Gateways to clinical trials. | 2008 Mar |
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Antiepileptogenic and antiictogenic effects of retigabine under conditions of rapid kindling: an ontogenic study. | 2008 Oct |
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Bimodal effects of the Kv7 channel activator retigabine on vascular K+ currents. | 2008 Sep |
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Expression and function of K(v)7 channels in murine myometrium throughout oestrous cycle. | 2009 Mar |
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11378159
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
Edited
Thu Jul 06 22:20:24 UTC 2023
by
admin
on
Thu Jul 06 22:20:24 UTC 2023
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Record UNII |
12G01I6BBU
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Validated (UNII)
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NDF-RT |
N0000182729
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DEA NO. |
2779
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EMA ASSESSMENT REPORTS |
TROBALT (AUTHORIZED: EPILEPSY)
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FDA ORPHAN DRUG |
639118
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WHO-VATC |
QN03AX21
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NCI_THESAURUS |
C264
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WHO-ATC |
N03AX21
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LIVERTOX |
NBK548304
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121892
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M5229
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8171
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Retigabine
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2601
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Ezogabine
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7545
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68584
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100000080573
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150812-12-7
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SS-10
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1112990
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N0000182728
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PRIMARY | Potassium Channel Openers [MoA] | ||
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DTXSID40164615
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DB04953
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CHEMBL41355
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12G01I6BBU
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URINE
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ORAL BIOAVAILABILITY | PHARMACOKINETIC |
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Volume of Distribution | PHARMACOKINETIC |
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