EZOGABINE DIHYDROCHLORIDE

US Previously Marketed

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H18FN3O2.2ClH
Molecular Weight	376.253
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=WSGFOWNASITQHJ-UHFFFAOYSA-N

InChI=1S/C16H18FN3O2.2ClH/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);2*1H

HIDE SMILES / InChI

Molecular Formula	C16H18FN3O2
Molecular Weight	303.3314
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	ClH
Molecular Weight	36.461
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 10 Target ID: CHEMBL2363063 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=21686305	Activator 1447		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 8583	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
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
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
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
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
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
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

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
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
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
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
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
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
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

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 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
7.9 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
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
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

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2A6 879 CYP2C8 1057 CYP2C19 2057 CYP2E1 1060 CYP3A4/5 296 P-gp 1741	UGT1A1 479 UGT1A3 470 UGT1A9 423 UGT1A4 399 UGT1A6 343 UGT1A7 249 UGT1A10 331 UGT2B4 278 UGT2B7 456 UGT2B15 236 CYP 450 32 P-gp 2052	CYP1A2 832 CYP3A4/5 133 CYP2C 17 P-gp 301

Drug as perpetrator

Target	Modality	Activity	Metabolite
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=149 Page: 149.0	likely	N-AMR 3
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=177 Page: 177.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
CYP2C 37	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=177 Page: 177.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
CYP3A4/5 357	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=177 Page: 177.0	no
CYP3A4/5 357	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
P-gp 1932	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=177 Page: 177.0	no
P-gp 1932	inhibitor 4027 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 32	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=14 Page: 14.0	no evidence
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=15 Page: 15.0	no
UGT1A10 331	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100.0	no
UGT1A6 343	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100.0	no
UGT1A7 249	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100.0	no
UGT2B15 236	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100.0	no
UGT2B4 278	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100.0	no
UGT2B7 456	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100.0	no
UGT1A3 470	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=14 Page: 14.0	yes
UGT1A4 399	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022345Orig1s000ClinPharmR.pdf#page=100 Page: 100.0	yes
UGT1A9 423	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022345s000lbl.pdf#page=14 Page: 14.0	yes
UGT1A1 479	substrate 4014 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 2263	inhibitor 2237 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
eMolecules	2729733	https://www.emolecules.com/cgi-bin/more?vid=2729733
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
Expression and function of K(v)7 channels in murine myometrium throughout oestrous cycle.	2009-03	18709386
Antiepileptogenic and antiictogenic effects of retigabine under conditions of rapid kindling: an ontogenic study.	2008-10	18503560
Retigabine, the specific KCNQ channel opener, blocks ectopic discharges in axotomized sensory fibres.	2008-09-15	18331780
Bimodal effects of the Kv7 channel activator retigabine on vascular K+ currents.	2008-09	18536747
Expression profile and characterisation of a truncated KCNQ5 splice variant.	2008-07-11	18457656
Retigabine reduces the excitability of unmyelinated peripheral human axons.	2008-06	18474382
Nervous system KV7 disorders: breakdown of a subthreshold brake.	2008-04-01	18238816
Gateways to clinical trials.	2008-03	18560631
The KCNQ/M-current modulates arterial baroreceptor function at the sensory terminal in rats.	2008-02-01	18048450
The mechanisms of neurodegenerative processes and current pharmacotherapy of Alzheimer's disease.	2008-02	18401056
Effect of the new antiepileptic drug retigabine in a rodent model of mania.	2008-01	18086455
The effectiveness of anticonvulsants in psychiatric disorders.	2008	18472486
A tale of switched functions: from cyclooxygenase inhibition to M-channel modulation in new diphenylamine derivatives.	2007-12-26	18159230
Retigabine: has the orphan found a home?	2007-12-01	18049722
Peripheral nerve hyperexcitability due to dominant-negative KCNQ2 mutations.	2007-11-27	17872363
Pharmacological comparison of anticonvulsant drugs in animal models of persistent pain and anxiety.	2007-10	17714743
The neuronal KCNQ channel opener retigabine inhibits locomotor activity and reduces forebrain excitatory responses to the psychostimulants cocaine, methylphenidate and phencyclidine.	2007-09-10	17628530
Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels.	2007-05	17456683
Phenytoin- and carbamazepine-resistant spontaneous bursting in rat entorhinal cortex is blocked by retigabine in vitro.	2007-05	17395429
Recruitment of apical dendritic T-type Ca2+ channels by backpropagating spikes underlies de novo intrinsic bursting in hippocampal epileptogenesis.	2007-04-15	17272342
Inactivation as a new regulatory mechanism for neuronal Kv7 channels.	2007-04-15	17237198
Randomized, multicenter, dose-ranging trial of retigabine for partial-onset seizures.	2007-04-10	17420403
Kv7.2-7.5 voltage-gated potassium channel (KCNQ2-5) opener, retigabine, reduces capsaicin-induced visceral pain in mice.	2007-02-14	17184917
Retigabine.	2007-01	17199031
Progress report on new antiepileptic drugs: a summary of the Eigth Eilat Conference (EILAT VIII).	2007-01	17158031
Somatodendritic Kv7/KCNQ/M channels control interspike interval in hippocampal interneurons.	2006-11-22	17122058
Antidystonic effects of Kv7 (KCNQ) channel openers in the dt sz mutant, an animal model of primary paroxysmal dystonia.	2006-11	17016514
The acrylamide (S)-1 differentially affects Kv7 (KCNQ) potassium channels.	2006-11	16904708
Kv7/KCNQ/M-channels in rat glutamatergic hippocampal axons and their role in regulation of excitability and transmitter release.	2006-10-01	16840518
An exploratory open trial on safety and efficacy of the anticonvulsant retigabine in acute manic patients.	2006-10	16974202
Retigabine-induced population primary afferent hyperpolarisation in vitro.	2006-09	16844148
The KCNQ channel opener retigabine inhibits the activity of mesencephalic dopaminergic systems of the rat.	2006-09	16775195
Ionic mechanisms of autorhythmic firing in rat cerebellar Golgi cells.	2006-08-01	16690702
Retigabine and flupirtine exert neuroprotective actions in organotypic hippocampal cultures.	2006-08	16697426
New antiepileptic drugs that are second generation to existing antiepileptic drugs.	2006-06	16732716
N-Glucuronidation of the antiepileptic drug retigabine: results from studies with human volunteers, heterologously expressed human UGTs, human liver, kidney, and liver microsomal membranes of Crigler-Najjar type II.	2006-06	16713428
Diverse mechanisms of antiepileptic drugs in the development pipeline.	2006-06	16621450
KCNQ channels mediate IKs, a slow K+ current regulating excitability in the rat node of Ranvier.	2006-05-15	16527853
KCNQ/Kv7 channel regulation of hippocampal gamma-frequency firing in the absence of synaptic transmission.	2006-05	16467425
Gateways to clinical trials.	2006-04	16810345
Pulmonary vasoconstrictor action of KCNQ potassium channel blockers.	2006-02-20	16504007
A spontaneous mutation involving Kcnq2 (Kv7.2) reduces M-current density and spike frequency adaptation in mouse CA1 neurons.	2006-02-15	16481438
The role of Gilbert's syndrome and frequent NAT2 slow acetylation polymorphisms in the pharmacokinetics of retigabine.	2006-01-13	16402080
[Voltage-activated potassium channels of the inhibitory interneurons of the hippocampus in culture].	2006	17333621
Retigabine: in partial seizures.	2006	16800718
Effects of M-current modulators on the excitability of immature rat spinal sensory and motor neurones.	2005-12	16367775
Effects of retigabine on the neurodegeneration and extracellular glutamate changes induced by 4-aminopyridine in rat hippocampus in vivo.	2005-12	16362775
Retigabine: bending potassium channels to our will.	2005-09-22	16175213
Effects of anticonvulsants on soman-induced epileptiform activity in the guinea-pig in vitro hippocampus.	2005-08-22	16054127
Ion channel defects in idiopathic epilepsies.	2005	16101452

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 `Mon Mar 31 23:26:51 GMT 2025` Edited by `admin` on `Mon Mar 31 23:26:51 GMT 2025`
Record UNII	WV9W9019AP
Record Status	`Validated (UNII)`
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Name

Type

Language

D-20443

Preferred Name

English

EZOGABINE DIHYDROCHLORIDE

Common Name

English

EZOGABINE DIHYDROCHLORIDE [MI]

Common Name

English

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

Systematic Name

English

N-(2-AMINO-4-(((4-FLUOROPHENYL)METHYL)AMINO)PHENYL)CARBAMIC ACID ETHYL ESTER DIHYDROCHLORIDE

Systematic Name

English

RETIGABINE DIHYDROCHLORIDE

Common Name

English

Code System Code Type Description

FDA UNII

WV9W9019AP