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 1335	Partial-onset seizures	1.60000000000000009 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	KCNQ (Kv7) potassium channel	Approved 7997	POTIGA Approved Use Indicated as adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments and for whom the benefits outweigh the risk of retinal abnormalities and potential decline in visual acuity Launch Date 1307664000000

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 Health Status: unhealthy Age Group: 30 years Sex: F 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) Health Status: unhealthy Age Group: 37.7 years (range: 18 –71 years) Sex: M+F 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 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 Health Status: unhealthy Age Group: 48 years Sex: F 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 Health Status: unhealthy Age Group: adult Sex: M+F 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 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 1318	inhibitor 1421	inhibitor 1360

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 761 CYP1A2 1268 CYP2A6 594 CYP2C19 1215 CYP2E1 761 CYP3A4/5 225 P-gp 1089	UGT1A1 358 UGT1A3 358 UGT1A9 327 UGT1A4 295 UGT1A6 258 UGT1A7 197 UGT1A10 247 UGT2B4 213 UGT2B7 329 UGT2B15 165 CYP 450 25 P-gp 1223	CYP1A2 618 CYP3A4/5 107 CYP2C 11 P-gp 225

Drug as perpetrator

Target	Modality	Activity	Metabolite
P-gp 1255	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=149 Page: 149	likely	N-AMR 2
CYP1A2 1406	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=177 Page: 177	no
CYP1A2 1406	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15	no
CYP2A6 625	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15	no
CYP2C 29	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=177 Page: 177	no
CYP2C19 1277	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15	no
CYP2C8 810	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15	no
CYP2C9 1362	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15	no
CYP2D6 1455	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15	no
CYP2E1 841	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15	no
CYP3A4/5 277	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=177 Page: 177	no
CYP3A4/5 277	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15	no
P-gp 1255	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=177 Page: 177	no
P-gp 1255	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15	no

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP 450 25	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=14 Page: 14	no evidence
P-gp 1223	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15	no
UGT1A10 247	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100	no
UGT1A6 258	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100	no
UGT1A7 197	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100	no
UGT2B15 165	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100	no
UGT2B4 213	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100	no
UGT2B7 329	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100	no
UGT1A3 358	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=14 Page: 14	yes
UGT1A4 295	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100	yes
UGT1A9 327	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=14 Page: 14	yes
UGT1A1 358	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=14 Page: 14	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

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1392	inhibitor 1374 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000PharmR.pdf#page=19 Page: 19

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:68584	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:68584
MolPort	MolPort-003-850-148	https://www.molport.com/shop/molecule-link/MolPort-003-850-148
ZINC	ZINC000000016154	http://zinc15.docking.org/substances/ZINC000000016154

PubMed

Title	Date	PubMed
Delayed sclerosis, neuroprotection, and limbic epileptogenesis after status epilepticus in the rat.	2002	12121301
Effects of the anticonvulsant retigabine on cultured cortical neurons: changes in electroresponsive properties and synaptic transmission.	2002 Apr	11901232
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
Pharmacokinetic interaction between retigabine and lamotrigine in healthy subjects.	2003 Apr	12698305
A medium-throughput functional assay of KCNQ2 potassium channels using rubidium efflux and atomic absorption spectrometry.	2003 Aug 15	12871719
The anticonvulsant retigabine attenuates nociceptive behaviours in rat models of persistent and neuropathic pain.	2003 Jan 24	12559370
Synergy between retigabine and GABA in modulating the convulsant site of the GABAA receptor complex.	2003 Mar 19	12620500
The anti-hyperalgesic activity of retigabine is mediated by KCNQ potassium channel activation.	2004 Apr	15007538
Retigabine stimulates human KCNQ2/Q3 channels in the presence of bupivacaine.	2004 Aug	15277926
KCNQ2 is a nodal K+ channel.	2004 Feb 4	14762142
M-current modulators alter rat spinal nociceptive transmission: an electrophysiological study in vitro.	2004 Mar	14975684
The KCNQ channel activator retigabine blocks haloperidol-induced c-Fos expression in the striatum of the rat.	2004 May 27	15158023
Progress report on new antiepileptic drugs: a summary of the Seventh Eilat Conference (EILAT VII).	2004 Sep-Oct	15570674
Voltage gated ion channels: targets for anticonvulsant drugs.	2005	15638775
The new anticonvulsant retigabine favors voltage-dependent opening of the Kv7.2 (KCNQ2) channel by binding to its activation gate.	2005 Apr	15662042
Effects of anticonvulsants on soman-induced epileptiform activity in the guinea-pig in vitro hippocampus.	2005 Aug 22	16054127
Effects of M-current modulators on the excitability of immature rat spinal sensory and motor neurones.	2005 Dec	16367775
Gateways to clinical trials.	2005 Jan-Feb	15834459
Anxiolytic effects of Maxipost (BMS-204352) and retigabine via activation of neuronal Kv7 channels.	2005 Jul	15814569
Retigabine: chemical synthesis to clinical application.	2005 Spring	15867950
[Voltage-activated potassium channels of the inhibitory interneurons of the hippocampus in culture].	2006	17333621
Retigabine: in partial seizures.	2006	16800718
Ionic mechanisms of autorhythmic firing in rat cerebellar Golgi cells.	2006 Aug 1	16690702
Diverse mechanisms of antiepileptic drugs in the development pipeline.	2006 Jun	16621450
KCNQ/Kv7 channel regulation of hippocampal gamma-frequency firing in the absence of synaptic transmission.	2006 May	16467425
KCNQ channels mediate IKs, a slow K+ current regulating excitability in the rat node of Ranvier.	2006 May 15	16527853
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
An exploratory open trial on safety and efficacy of the anticonvulsant retigabine in acute manic patients.	2006 Oct	16974202
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
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
The mechanisms of neurodegenerative processes and current pharmacotherapy of Alzheimer's disease.	2008 Feb	18401056
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