EZOGABINE

US Previously Marketed

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 Search

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
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022345s011lbl.pdf
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
KCNQ (Kv7) potassium channel 6 Target ID: CHEMBL2363063 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=21686305	Activator 1343		1.6 µM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Partial-onset seizures 5 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022345s011lbl.pdf	Secondary		Approved 8043	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 1.30766406E12

C_max

Value	Dose	Analyte	Population
414 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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	Analyte	Population
1831 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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

T_1/2

Value	Dose	Analyte	Population
8.4 h OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf	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: https://pubmed.ncbi.nlm.nih.gov/25006968	unhealthy, 30 years n = 2 Health Status: unhealthy Condition: epilepsy Age Group: 30 years Sex: F Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/25006968	Disc. AE: Mucocutaneous disorder... AEs leading to discontinuation/dose reduction: Mucocutaneous disorder (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/25006968
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: https://pubmed.ncbi.nlm.nih.gov/21451152	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: https://pubmed.ncbi.nlm.nih.gov/21451152	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: https://pubmed.ncbi.nlm.nih.gov/21451152
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: https://pubmed.ncbi.nlm.nih.gov/26909536	unhealthy, 48 years n = 1 Health Status: unhealthy Condition: epilepsy Age Group: 48 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/26909536	Disc. AE: Maculopathy... AEs leading to discontinuation/dose reduction: Maculopathy (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/26909536
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf	unhealthy, adult n = 813 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 813 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf	Disc. AE: Dizziness, Confusional state... AEs leading to discontinuation/dose reduction: Dizziness (6%) Confusional state (4%) Fatigue (3%) Somnolence (3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf	unhealthy Health Status: unhealthy Condition: epilepsy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf	Other AEs: Agitation, Aggressive behavior... Other AEs: Agitation Aggressive behavior Irritability Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inhibitor 1604	inhibitor 1702	inhibitor 1475

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1383 CYP2A6 627 CYP2C8 818 CYP2C19 1325 CYP2E1 790 CYP3A4/5 241 P-gp 1330	UGT1A1 393 UGT1A3 397 UGT1A9 357 UGT1A4 330 UGT1A6 289 UGT1A7 221 UGT1A10 273 UGT2B4 233 UGT2B7 362 UGT2B15 191 CYP 450 28 P-gp 1400	CYP1A2 637 CYP3A4/5 108 CYP2C 11 P-gp 248

Drug as perpetrator

Target	Modality	Activity	Metabolite
P-gp 1514	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=149 Page: 149.0	likely	N-AMR 2
CYP1A2 1532	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=177 Page: 177.0	no
CYP1A2 1532	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
CYP2A6 659	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
CYP2C 30	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=177 Page: 177.0	no
CYP2C19 1392	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
CYP2C8 865	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
CYP2C9 1648	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
CYP2D6 1738	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
CYP2E1 871	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
CYP3A4/5 293	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=177 Page: 177.0	no
CYP3A4/5 293	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
P-gp 1514	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=177 Page: 177.0	no
P-gp 1514	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP 450 28	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=14 Page: 14.0	no evidence
P-gp 1400	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
UGT1A10 273	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100.0	no
UGT1A6 289	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100.0	no
UGT1A7 221	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100.0	no
UGT2B15 191	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100.0	no
UGT2B4 233	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100.0	no
UGT2B7 362	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100.0	no
UGT1A3 397	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=14 Page: 14.0	yes
UGT1A4 330	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100.0	yes
UGT1A9 357	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=14 Page: 14.0	yes
UGT1A1 393	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=14 Page: 14.0	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=14 Page: 14.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1507	inhibitor 1489 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000PharmR.pdf#page=19 Page: 19.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:68584	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:68584
ChemicalBook	CB7506804	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7506804
MolPort	MolPort-003-850-148	https://www.molport.com/shop/molecule-link/MolPort-003-850-148
ZINC	ZINC000000016154	http://zinc15.docking.org/substances/ZINC000000016154
eMolecules	2729733	https://www.emolecules.com/cgi-bin/more?vid=2729733

PubMed

Title	Date	PubMed
		252160861
A thallium-sensitive, fluorescence-based assay for detecting and characterizing potassium channel modulators in mammalian cells.	2004 Dec	15634793
Urodynamic effects of the K+ channel (KCNQ) opener retigabine in freely moving, conscious rats.	2004 Nov	15540788
Progress report on new antiepileptic drugs: a summary of the Seventh Eilat Conference (EILAT VII).	2004 Sep-Oct	15570674
Ion channel defects in idiopathic epilepsies.	2005	16101452
Voltage gated ion channels: targets for anticonvulsant drugs.	2005	15638775
Effects of M-current modulators on the excitability of immature rat spinal sensory and motor neurones.	2005 Dec	16367775
Effects of retigabine on the neurodegeneration and extracellular glutamate changes induced by 4-aminopyridine in rat hippocampus in vivo.	2005 Dec	16362775
Gateways to clinical trials.	2005 Jan-Feb	15834459
Presynaptic inhibition of transmitter release from rat sympathetic neurons by bradykinin.	2005 Jun	15934932
The KCNQ5 potassium channel from mouse: a broadly expressed M-current like potassium channel modulated by zinc, pH, and volume changes.	2005 Sep 13	15963599
Retigabine: bending potassium channels to our will.	2005 Sep-Oct	16175213
[Voltage-activated potassium channels of the inhibitory interneurons of the hippocampus in culture].	2006	17333621
Retigabine: in partial seizures.	2006	16800718
Gateways to clinical trials.	2006 Apr	16810345
Ionic mechanisms of autorhythmic firing in rat cerebellar Golgi cells.	2006 Aug 1	16690702
New antiepileptic drugs that are second generation to existing antiepileptic drugs.	2006 Jun	16732716
KCNQ/Kv7 channel regulation of hippocampal gamma-frequency firing in the absence of synaptic transmission.	2006 May	16467425
The role of Gilbert's syndrome and frequent NAT2 slow acetylation polymorphisms in the pharmacokinetics of retigabine.	2006 May-Jun	16402080
Antidystonic effects of Kv7 (KCNQ) channel openers in the dt sz mutant, an animal model of primary paroxysmal dystonia.	2006 Nov	17016514
The acrylamide (S)-1 differentially affects Kv7 (KCNQ) potassium channels.	2006 Nov	16904708
Somatodendritic Kv7/KCNQ/M channels control interspike interval in hippocampal interneurons.	2006 Nov 22	17122058
An exploratory open trial on safety and efficacy of the anticonvulsant retigabine in acute manic patients.	2006 Oct	16974202
Kv7/KCNQ/M-channels in rat glutamatergic hippocampal axons and their role in regulation of excitability and transmitter release.	2006 Oct 1	16840518
Retigabine-induced population primary afferent hyperpolarisation in vitro.	2006 Sep	16844148
Randomized, multicenter, dose-ranging trial of retigabine for partial-onset seizures.	2007 Apr 10	17420403
Recruitment of apical dendritic T-type Ca2+ channels by backpropagating spikes underlies de novo intrinsic bursting in hippocampal epileptogenesis.	2007 Apr 15	17272342
Inactivation as a new regulatory mechanism for neuronal Kv7 channels.	2007 Apr 15	17237198
A tale of switched functions: from cyclooxygenase inhibition to M-channel modulation in new diphenylamine derivatives.	2007 Dec 26	18159230
Kv7.2-7.5 voltage-gated potassium channel (KCNQ2-5) opener, retigabine, reduces capsaicin-induced visceral pain in mice.	2007 Feb 14	17184917
Retigabine.	2007 Jan	17199031
Progress report on new antiepileptic drugs: a summary of the Eigth Eilat Conference (EILAT VIII).	2007 Jan	17158031
Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels.	2007 May	17456683
Phenytoin- and carbamazepine-resistant spontaneous bursting in rat entorhinal cortex is blocked by retigabine in vitro.	2007 May	17395429
Peripheral nerve hyperexcitability due to dominant-negative KCNQ2 mutations.	2007 Nov 27	17872363
Retigabine: has the orphan found a home?	2007 Nov-Dec	18049722
Pharmacological comparison of anticonvulsant drugs in animal models of persistent pain and anxiety.	2007 Oct	17714743
The neuronal KCNQ channel opener retigabine inhibits locomotor activity and reduces forebrain excitatory responses to the psychostimulants cocaine, methylphenidate and phencyclidine.	2007 Sep 10	17628530
The effectiveness of anticonvulsants in psychiatric disorders.	2008	18472486
Nervous system KV7 disorders: breakdown of a subthreshold brake.	2008 Apr 1	18238816
The mechanisms of neurodegenerative processes and current pharmacotherapy of Alzheimer's disease.	2008 Feb	18401056
The KCNQ/M-current modulates arterial baroreceptor function at the sensory terminal in rats.	2008 Feb 1	18048450
Effect of the new antiepileptic drug retigabine in a rodent model of mania.	2008 Jan	18086455
Expression profile and characterisation of a truncated KCNQ5 splice variant.	2008 Jul 11	18457656
Retigabine reduces the excitability of unmyelinated peripheral human axons.	2008 Jun	18474382
Gateways to clinical trials.	2008 Mar	18560631
Antiepileptogenic and antiictogenic effects of retigabine under conditions of rapid kindling: an ontogenic study.	2008 Oct	18503560
Bimodal effects of the Kv7 channel activator retigabine on vascular K+ currents.	2008 Sep	18536747
Retigabine, the specific KCNQ channel opener, blocks ectopic discharges in axotomized sensory fibres.	2008 Sep 15	18331780
Expression and function of K(v)7 channels in murine myometrium throughout oestrous cycle.	2009 Mar	18709386

Patents

Sample Use Guides

In Vivo Use Guide

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

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

Official Name

English

RETIGABINE

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