EZOGABINE HYDROCHLORIDE

US Previously Marketed

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H18FN3O2.ClH
Molecular Weight	339.792
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CCOC(=O)NC1=CC=C(NCC2=CC=C(F)C=C2)C=C1N

InChI

InChIKey=IRTSOTYNVNKKNY-UHFFFAOYSA-N

InChI=1S/C16H18FN3O2.ClH/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);1H

HIDE SMILES / InChI

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 10 Target ID: CHEMBL2363063 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=21686305	Activator 1430		1.6 µM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Partial-onset seizures 6 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022345s011lbl.pdf	Secondary		Approved 8429	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 2011

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 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2C8 911 CYP2C19 1478 CYP2E1 882 CYP3A4/5 278 P-gp 1461	UGT1A1 418 UGT1A3 422 UGT1A9 380 UGT1A4 347 UGT1A6 307 UGT1A7 236 UGT1A10 291 UGT2B4 249 UGT2B7 389 UGT2B15 203 CYP 450 31 P-gp 1537	CYP1A2 701 CYP3A4/5 124 CYP2C 15 P-gp 257

Drug as perpetrator

Target	Modality	Activity	Metabolite
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=149 Page: 149.0	likely	N-AMR 3
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=177 Page: 177.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
CYP2C 34	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=177 Page: 177.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
CYP3A4/5 335	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=177 Page: 177.0	no
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
P-gp 1650	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=177 Page: 177.0	no
P-gp 1650	inhibitor 3277 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 31	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=14 Page: 14.0	no evidence
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
UGT1A10 291	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100.0	no
UGT1A6 307	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100.0	no
UGT1A7 236	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100.0	no
UGT2B15 203	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100.0	no
UGT2B4 249	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100.0	no
UGT2B7 389	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100.0	no
UGT1A3 422	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=14 Page: 14.0	yes
UGT1A4 347	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100.0	yes
UGT1A9 380	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=14 Page: 14.0	yes
UGT1A1 418	substrate 3367 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 1647	inhibitor 1626 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
Potassium channels: how genetic studies of epileptic syndromes open paths to new therapeutic targets and drugs.	2001	11887968
Retigabine (ASTA Medica).	2001 Jan	16034707
Novel anticonvulsant medications in development.	2002 Oct	12387702
Progress report on new antiepileptic drugs: a summary of the Sixth Eilat Conference (EILAT VI).	2002 Sep	12350382
The therapeutic potential of neuronal KCNQ channel modulators.	2003 Dec	14640909
Retigabine stimulates human KCNQ2/Q3 channels in the presence of bupivacaine.	2004 Aug	15277926
Gateways to clinical trials.	2005 Jan-Feb	15834459
Retigabine: bending potassium channels to our will.	2005 Sep-Oct	16175213
Gateways to clinical trials.	2006 Apr	16810345
Diverse mechanisms of antiepileptic drugs in the development pipeline.	2006 Jun	16621450
Somatodendritic Kv7/KCNQ/M channels control interspike interval in hippocampal interneurons.	2006 Nov 22	17122058
Kv7/KCNQ/M-channels in rat glutamatergic hippocampal axons and their role in regulation of excitability and transmitter release.	2006 Oct 1	16840518
Progress report on new antiepileptic drugs: a summary of the Eigth Eilat Conference (EILAT VIII).	2007 Jan	17158031
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
The effectiveness of anticonvulsants in psychiatric disorders.	2008	18472486
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
Gateways to clinical trials.	2008 Mar	18560631
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.

Name

Type

Language

EZOGABINE HYDROCHLORIDE

Common Name

English

CARBAMIC ACID, N-(2-AMINO-4-(((4-FLUOROPHENYL)METHYL)AMINO)PHENYL)-, ETHYL ESTER, HYDROCHLORIDE (1:1)

Systematic Name

English

ETHYL N-(2-AMINO-4-((4-FLUOROPHENYL)METHYLAMINO)PHENYL)CARBAMATE HYDROCHLORIDE

Systematic Name

English

Code System Code Type Description

PUBCHEM

10020110

Created by admin on Sat Dec 16 18:37:19 GMT 2023 , Edited by admin on Sat Dec 16 18:37:19 GMT 2023

PRIMARY

FDA UNII

UU67G9UH78

Created by admin on Sat Dec 16 18:37:19 GMT 2023 , Edited by admin on Sat Dec 16 18:37:19 GMT 2023

PRIMARY

CAS

1215347-18-4

Created by admin on Sat Dec 16 18:37:19 GMT 2023 , Edited by admin on Sat Dec 16 18:37:19 GMT 2023

PRIMARY

ACTIVE MOIETY


					12G01I6BBU

EZOGABINE

SUBSTANCE RECORD


					UU67G9UH78

EZOGABINE HYDROCHLORIDE

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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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
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: 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

Details

SMILES

InChI

DescriptionSources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022345s011lbl.pdfCurator'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

CNS Activity

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Cmax

AUC

T1/2

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

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

C_max

T_1/2

Drug as perpetrator