Details of the Drug

General Information of Drug (ID: DMGNYIH)

Drug Name

Retigabine

Synonyms

Ezogabine; Potiga; Trobalt; Retigabine [USAN]; D 20443; D 23129; ADD-230001; D-20443; D-23129; GKE-841; KE-0201; Ethyl 2-amino-4-((p-fluorobenzyl)amino)carbanilate; Ethyl N-[2-amino-4-[(4-fluorophenyl)methylamino]phenyl]carbamate; [2-Amino-4-[[(4-fluorophenyl)methyl]amino]phenyl]-carbamate; Ethyl N-(2-amino-4-(4-fluorobenzylamino)phenyl)carbamate hydrochloride; N-(2-Amino-4-(4-fluorobenzylamino)phenyl)carbamic acid ethyl ester; Ethyl (2-amino-4-(((4-fluorophenyl)methyl)amino)phenyl)carbamate; N-(2-Amino-4-(4-fluorobenzylamino)-phenyl) carbamic acid ethyl ester; Carbamic acid, (2-amino-4-(((4-fluorophenyl)methyl)amino)phenyl)-, ethyl ester

Indication

Disease Entry	ICD 11	Status	REF
Behcet disease	4A62	Approved	[1]
Epilepsy	8A60-8A68	Withdrawn from market	[2]
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Therapeutic Class

Anticonvulsants

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

303.33

Logarithm of the Partition Coefficient (xlogp)

2.8

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Clearance: The drug present in the plasma can be removed from the body at the rate of 8.3 mL/min/kg [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 7.5 hours [3]
Metabolism: The drug is metabolized via phase II hepatic N-glucurodination and acetylation []
Unbound Fraction: The unbound fraction of drug in plasma is 0.2% [3]
Vd: The volume of distribution (Vd) of drug is 8.7 L/kg []

Chemical Identifiers

Formula: C16H18FN3O2
IUPAC Name: ethyl N-[2-amino-4-[(4-fluorophenyl)methylamino]phenyl]carbamate
Canonical SMILES: CCOC(=O)NC1=C(C=C(C=C1)NCC2=CC=C(C=C2)F)N
InChI: 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)
InChIKey: PCOBBVZJEWWZFR-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 121892
ChEBI ID: CHEBI:68584
CAS Number: 150812-12-7
DrugBank ID: DB04953
TTD ID: D0X7GL
VARIDT ID: DR00700
INTEDE ID: DR1407
ACDINA ID: D00263

Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Voltage-gated potassium channel Kv7 (KCNQ)	TTQ29KF	NOUNIPROTAC	Activator	[2]
Voltage-gated potassium channel Kv7.3 (KCNQ3)	TTIVDM3	KCNQ3_HUMAN	Modulator	[4]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Substrate	[5]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Substrate	[6]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Substrate	[5]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Substrate	[5]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Gene/Protein Processing	[7]
Potassium voltage-gated channel subfamily KQT member 2 (KCNQ2)	OT3CXQJT	KCNQ2_HUMAN	Gene/Protein Processing	[8]
Potassium voltage-gated channel subfamily KQT member 3 (KCNQ3)	OTXVBEED	KCNQ3_HUMAN	Drug Response	[8]
Potassium voltage-gated channel subfamily KQT member 4 (KCNQ4)	OT29B58J	KCNQ4_HUMAN	Gene/Protein Processing	[9]
Sodium channel protein type 5 subunit alpha (SCN5A)	OTGYZWR6	SCN5A_HUMAN	Gene/Protein Processing	[7]
SUMO-activating enzyme subunit 1 (SAE1)	OT18HFX5	SAE1_HUMAN	Gene/Protein Processing	[10]
Voltage-dependent L-type calcium channel subunit alpha-1C (CACNA1C)	OT6KFNMS	CAC1C_HUMAN	Gene/Protein Processing	[7]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Behcet disease

ICD Disease Classification

4A62

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Voltage-gated potassium channel Kv7 (KCNQ)	DTT	NO-GeName	6.24E-01	0.11	0.85
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DME	UGT1A1	4.53E-01	4.14E-02	1.83E-01
Cytochrome P450 1A1 (CYP1A1)	DME	CYP1A1	7.84E-01	-1.03E-01	-4.48E-01

Molecular Expression Atlas (MEA)

MEA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Retigabine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Major	Increased risk of prolong QT interval by the combination of Retigabine and Ivosidenib.	Acute myeloid leukaemia [2A60]	[11]
Midostaurin	DMI6E0R	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and Midostaurin.	Acute myeloid leukaemia [2A60]	[12]
Arn-509	DMT81LZ	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and Arn-509.	Acute myeloid leukaemia [2A60]	[13]
Oliceridine	DM6MDCF	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and Oliceridine.	Acute pain [MG31]	[14]
Ivabradine	DM0L594	Major	Increased risk of ventricular arrhythmias by the combination of Retigabine and Ivabradine.	Angina pectoris [BA40]	[13]
Bedaquiline	DM3906J	Major	Increased risk of prolong QT interval by the combination of Retigabine and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[15]
Levalbuterol	DM5YBO1	Moderate	Increased risk of ventricular arrhythmias by the combination of Retigabine and Levalbuterol.	Asthma [CA23]	[16]
Eribulin	DM1DX4Q	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and Eribulin.	Breast cancer [2C60-2C6Y]	[12]
PF-04449913	DMSB068	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and PF-04449913.	Chronic myelomonocytic leukaemia [2A40]	[17]
Olodaterol	DM62B78	Moderate	Increased risk of ventricular arrhythmias by the combination of Retigabine and Olodaterol.	Chronic obstructive pulmonary disease [CA22]	[18]
Vilanterol	DMF5EK1	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and Vilanterol.	Chronic obstructive pulmonary disease [CA22]	[16]
Indacaterol	DMQJHR7	Moderate	Increased risk of ventricular arrhythmias by the combination of Retigabine and Indacaterol.	Chronic obstructive pulmonary disease [CA22]	[18]
Levomilnacipran	DMV26S8	Moderate	Antagonize the effect of Retigabine when combined with Levomilnacipran.	Chronic pain [MG30]	[19]
Pasireotide	DMHM7JS	Major	Increased risk of prolong QT interval by the combination of Retigabine and Pasireotide.	Cushing syndrome [5A70]	[12]
Osilodrostat	DMIJC9X	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and Osilodrostat.	Cushing syndrome [5A70]	[11]
Vilazodone	DM4LECQ	Moderate	Antagonize the effect of Retigabine when combined with Vilazodone.	Depression [6A70-6A7Z]	[19]
Vortioxetine	DM6F1PU	Moderate	Antagonize the effect of Retigabine when combined with Vortioxetine.	Depression [6A70-6A7Z]	[19]
Desvenlafaxine	DMHD4PE	Moderate	Antagonize the effect of Retigabine when combined with Desvenlafaxine.	Depression [6A70-6A7Z]	[19]
Esketamine	DMVU687	Moderate	Additive CNS depression effects by the combination of Retigabine and Esketamine.	Depression [6A70-6A7Z]	[20]
Deutetrabenazine	DMUPFLI	Moderate	Additive CNS depression effects by the combination of Retigabine and Deutetrabenazine.	Dystonic disorder [8A02]	[21]
Ingrezza	DMVPLNC	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and Ingrezza.	Dystonic disorder [8A02]	[22]
Ripretinib	DM958QB	Moderate	Decreased clearance of Retigabine due to the transporter inhibition by Ripretinib.	Gastrointestinal stromal tumour [2B5B]	[20]
Brentuximab vedotin	DMWLC57	Moderate	Decreased clearance of Retigabine due to the transporter inhibition by Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[23]
Fostemsavir	DM50ILT	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and Fostemsavir.	Human immunodeficiency virus disease [1C60-1C62]	[24]
Rilpivirine	DMJ0QOW	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and Rilpivirine.	Human immunodeficiency virus disease [1C60-1C62]	[12]
Polyethylene glycol	DM4I1JP	Moderate	Increased risk of ventricular arrhythmias by the combination of Retigabine and Polyethylene glycol.	Irritable bowel syndrome [DD91]	[13]
Crizotinib	DM4F29C	Major	Increased risk of prolong QT interval by the combination of Retigabine and Crizotinib.	Lung cancer [2C25]	[25]
Ceritinib	DMB920Z	Major	Increased risk of prolong QT interval by the combination of Retigabine and Ceritinib.	Lung cancer [2C25]	[12]
Osimertinib	DMRJLAT	Major	Increased risk of prolong QT interval by the combination of Retigabine and Osimertinib.	Lung cancer [2C25]	[26]
Selpercatinib	DMZR15V	Major	Increased risk of prolong QT interval by the combination of Retigabine and Selpercatinib.	Lung cancer [2C25]	[27]
Lumefantrine	DM29GAD	Major	Increased risk of prolong QT interval by the combination of Retigabine and Lumefantrine.	Malaria [1F40-1F45]	[20]
Inotuzumab ozogamicin	DMAC130	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and Inotuzumab ozogamicin.	Malignant haematopoietic neoplasm [2B33]	[13]
Vemurafenib	DM62UG5	Major	Increased risk of prolong QT interval by the combination of Retigabine and Vemurafenib.	Melanoma [2C30]	[12]
LGX818	DMNQXV8	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and LGX818.	Melanoma [2C30]	[28]
Allopregnanolone	DMNLHAC	Moderate	Additive CNS depression effects by the combination of Retigabine and Allopregnanolone.	Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z]	[29]
Lasmiditan	DMXLVDT	Moderate	Additive CNS depression effects by the combination of Retigabine and Lasmiditan.	Migraine [8A80]	[30]
Panobinostat	DM58WKG	Major	Increased risk of prolong QT interval by the combination of Retigabine and Panobinostat.	Multiple myeloma [2A83]	[31]
Fingolimod	DM5JVAN	Major	Increased risk of ventricular arrhythmias by the combination of Retigabine and Fingolimod.	Multiple sclerosis [8A40]	[12]
Ozanimod	DMT6AM2	Major	Increased risk of ventricular arrhythmias by the combination of Retigabine and Ozanimod.	Multiple sclerosis [8A40]	[32]
Romidepsin	DMT5GNL	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and Romidepsin.	Mycosis fungoides [2B01]	[14]
Entrectinib	DMMPTLH	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and Entrectinib.	Non-small cell lung cancer [2C25]	[13]
Rucaparib	DM9PVX8	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and Rucaparib.	Ovarian cancer [2C73]	[12]
Triclabendazole	DMPWGBR	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and Triclabendazole.	Parasitic worm infestation [1F90]	[14]
Pimavanserin	DMR7IVC	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and Pimavanserin.	Parkinsonism [8A00]	[33]
Macimorelin	DMQYJIR	Major	Increased risk of prolong QT interval by the combination of Retigabine and Macimorelin.	Pituitary gland disorder [5A60-5A61]	[34]
Lefamulin	DME6G97	Major	Increased risk of prolong QT interval by the combination of Retigabine and Lefamulin.	Pneumonia [CA40]	[11]
Degarelix	DM3O8QY	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and Degarelix.	Prostate cancer [2C82]	[13]
ABIRATERONE	DM8V75C	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and ABIRATERONE.	Prostate cancer [2C82]	[13]
Enzalutamide	DMGL19D	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and Enzalutamide.	Prostate cancer [2C82]	[13]
Relugolix	DMK7IWL	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and Relugolix.	Prostate cancer [2C82]	[13]
Amisulpride	DMSJVAM	Major	Increased risk of prolong QT interval by the combination of Retigabine and Amisulpride.	Schizophrenia [6A20]	[35]
Asenapine	DMSQZE2	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and Asenapine.	Schizophrenia [6A20]	[12]
LEE011	DMMX75K	Major	Increased risk of prolong QT interval by the combination of Retigabine and LEE011.	Solid tumour/cancer [2A00-2F9Z]	[12]
Vandetanib	DMRICNP	Major	Increased risk of prolong QT interval by the combination of Retigabine and Vandetanib.	Solid tumour/cancer [2A00-2F9Z]	[12]
Triptorelin	DMTK4LS	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and Triptorelin.	Solid tumour/cancer [2A00-2F9Z]	[13]
Pitolisant	DM8RFNJ	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and Pitolisant.	Somnolence [MG42]	[12]
Telavancin	DM58VQX	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and Telavancin.	Staphylococcal/streptococcal disease [1B5Y]	[12]
Lenvatinib	DMB1IU4	Moderate	Increased risk of prolong QT interval by the combination of Retigabine and Lenvatinib.	Thyroid cancer [2D10]	[12]
Cabozantinib	DMIYDT4	Major	Increased risk of prolong QT interval by the combination of Retigabine and Cabozantinib.	Thyroid cancer [2D10]	[13]
Betrixaban	DM2C4RF	Moderate	Decreased clearance of Retigabine due to the transporter inhibition by Betrixaban.	Venous thromboembolism [BD72]	[36]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Caprylic acid	E00017	379	Emulsifying agent; Flavoring agent; Surfactant
FD&C blue no. 2	E00446	2723854	Colorant
Carmellose sodium	E00625	Not Available	Disintegrant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Magnesium stearate	E00208	11177	lubricant
Polyvinyl alcohol	E00666	Not Available	Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Soybean lecithin	E00637	Not Available	Other agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Ezogabine 400 mg tablet	400 mg	Oral Tablet	Oral
Ezogabine 50 mg tablet	50 mg	Oral Tablet	Oral
Ezogabine 300 mg tablet	300 mg	Oral Tablet	Oral
Ezogabine 200 mg tablet	200 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	Clinical pipeline report, company report or official report of GlaxoSmithKline.
2	Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
3	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4	The urinary safety profile and secondary renal effects of retigabine (ezogabine): a first-in-class antiepileptic drug that targets KCNQ (K(v)7) potassium channels. Epilepsia. 2012 Apr;53(4):606-12.
5	Retigabine N-glucuronidation and its potential role in enterohepatic circulation. Drug Metab Dispos. 1999 May;27(5):605-12.
6	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. Metabolism. 2006 Jun;55(6):711-21.
7	Modulation of the heart's electrical properties by the anticonvulsant drug retigabine. Toxicol Appl Pharmacol. 2017 Aug 15;329:309-317. doi: 10.1016/j.taap.2017.06.018. Epub 2017 Jun 20.
8	The Sensorless Pore Module of Voltage-gated K+ Channel Family 7 Embodies the Target Site for the Anticonvulsant Retigabine. J Biol Chem. 2016 Feb 5;291(6):2931-7. doi: 10.1074/jbc.M115.683185. Epub 2015 Dec 1.
9	The acrylamide (S)-1 differentially affects Kv7 (KCNQ) potassium channels. Neuropharmacology. 2006 Nov;51(6):1068-77.
10	The SUMO-specific protease SENP2 plays an essential role in the regulation of Kv7.2 and Kv7.3 potassium channels. J Biol Chem. 2021 Oct;297(4):101183. doi: 10.1016/j.jbc.2021.101183. Epub 2021 Sep 10.
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18	Bengtsson B, Fagerstrom PO "Extrapulmonary effects of terbutaline during prolonged administration." Clin Pharmacol Ther 31 (1982): 726-32. [PMID: 7042176]
19	Belcastro V, Costa C, Striano P "Levetiracetam-associated hyponatremia." Seizure 17 (2008): 389-90. [PMID: 18584781]
20	Cerner Multum, Inc. "Australian Product Information.".
21	Product Information. Austedo (deutetrabenazine). Teva Pharmaceuticals USA, North Wales, PA.
22	Product Information. Ingrezza (valbenazine). Neurocrine Biosciences, Inc., San Diego, CA.
23	Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
24	Product Information. Rukobia (fostemsavir). ViiV Healthcare, Research Triangle Park, NC.
25	Product Information. Xalkori (crizotinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
26	Product Information. Tagrisso (osimertinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
27	Product Information. Retevmo (selpercatinib). Lilly, Eli and Company, Indianapolis, IN.
28	Product Information. Braftovi (encorafenib). Array BioPharma Inc., Boulder, CO.
29	Product Information. Zulresso (brexanolone). Sage Therapeutics, Inc., Cambridge, MA.
30	Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
31	Product Information. Farydak (panobinostat). Novartis Pharmaceuticals, East Hanover, NJ.
32	Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.
33	Product Information. Nuplazid (pimavanserin). Accelis Pharma, East Windsor, NJ.
34	Product Information. Macrilen (macimorelin). Aeterna Zentaris, Charleston, SC.
35	Product Information. Barhemsys (amisulpride). Acacia Pharma, Inc, Indianapolis, IN.
36	Product Information. Bevyxxa (betrixaban). Portola Pharmaceuticals, South San Francisco, CA.