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Identification
NameEzogabine
Accession NumberDB04953
TypeSmall Molecule
GroupsApproved
Description

Ezogabine (D23129) is a close structural analog of the centrally acting analgesic flupitrine. It is a neuronal potassium channel opener being developed as a first-in-class antiepileptic drug (AED) and is currently being studied in Phase 3 trials as an adjunctive treatment for partial-onset seizures in adult patients with refractory epilepsy. FDA approved in June 10, 2011 under the name of ezogabine.

Structure
Thumb
Synonyms
D-23129
Ethyl {2-amino-4-[(4-fluorobenzyl)amino]phenyl}carbamate
Ethyl 2-amino-4-((P-fluorobenzyl)amino)carbanilate
EZG
N-(2-Amino-4-(4-fluorobenzylamino)-phenyl) carbamic acid ethyl ester
N-(2-Amino-4-(4-fluorobenzylamino)phenyl)carbamic acid ethyl ester
Potiga
Retigabine
RTG
External Identifiers
  • D-23129
  • D23129
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Potigatablet, film coated50 mg/1oralGlaxo Smith Kline Llc2012-04-192016-04-23Us
Potigatablet, film coated400 mg/1oralGlaxo Smith Kline Llc2012-04-192016-04-23Us
Potigatablet, film coated300 mg/1oralGlaxo Smith Kline Llc2012-04-192016-04-23Us
Potigatablet, film coated200 mg/1oralGlaxo Smith Kline Llc2012-04-192016-04-23Us
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII12G01I6BBU
CAS number150812-12-7
WeightAverage: 303.3314
Monoisotopic: 303.13830504
Chemical FormulaC16H18FN3O2
InChI KeyInChIKey=PCOBBVZJEWWZFR-UHFFFAOYSA-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)
IUPAC Name
ethyl N-(2-amino-4-{[(4-fluorophenyl)methyl]amino}phenyl)carbamate
SMILES
CCOC(=O)NC1=C(N)C=C(NCC2=CC=C(F)C=C2)C=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylcarbamates. These are compounds containing a phenylazide moiety, which consists of a carbamic acid substituent attached to a phenyl group.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenylcarbamates
Direct ParentPhenylcarbamates
Alternative Parents
Substituents
  • Phenylcarbamate
  • Phenylalkylamine
  • Substituted aniline
  • Phenylmethylamine
  • Benzylamine
  • Aralkylamine
  • Secondary aliphatic/aromatic amine
  • Halobenzene
  • Fluorobenzene
  • Aniline
  • Primary aromatic amine
  • Aryl halide
  • Aryl fluoride
  • Secondary amine
  • Monocarboxylic acid or derivatives
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationAdjuvant treatment of partial-onset seizures.
PharmacodynamicsAs compared to other antiepileptic agents, ezogabine is unique in that it selectively activates potassium ion channels Kv 7.2-Kv7.5 and not cardiac Kv 7.1, thereby avoiding cardiac side effects. The antiepileptics, as a drug class, are routinely used in the treatment of a number of disease states in addition to epilepsy. Ezogabine is highly efficacious in a broad-spectrum of in vivo epilepsy and seizure models. A comparison of antiepileptic form activity of ezogabine with that of conventional anticonvulsants in in vitro models suggests that retigabine is especially likely to be useful in the treatment of pharmacoresistant epilepsy. Retigabine clearly attenuates pain-like behaviors in various animal models of neuropathic pain; it may also prove to be useful in treatment of clinical anxiety disorders. Clinical data obtained thus far indicate that retigabine is well tolerated in humans when titrated up to its therapeutic dose range. No tolerance, drug dependence, or withdrawal liability has been reported. Thus, retigabine may prove to be useful in the treatment of a diverse range of disease states in which neuronal hyperexcitability is a common underlying factor.
Mechanism of actionEzogabine has a novel mechanism of action that involves opening of neuronal Kv7.2-7.5 (formerly KCNQ2-5) voltage activated potassium channels. These channels (primarily Kv7.2/7.3) enable generation of the M-current, a sub-threshold potassium current that serves to stabilize the membrane potential and control neuronal excitability. In addition to acting on potassium ion channels, retigabine also affects GABA neurotransmission in the GABA-A receptor, which is a key inhibitory receptor in the central nervous system and is implicated in epilepsy. Malfunctioning of the GABA-A receptor leads to hyperexcitability in the brain, which causes seizures, making this receptor an important target for antiepileptic therapeutics. Apart from increasing the concentration of GABA in the brain (by either enhancing GABA synthesis or blocking GABA metabolism), retigabine allosterically potentiates GABA-induced current in rat cortical neurons in a concentration-dependent manner. Numerous studies have demonstrated that retigabine is effective in a broad spectrum of in vivo epilepsy and seizure models.
Related Articles
AbsorptionRapidly absorbed and distributed, with an absolute oral bioavailability of 60%. Pharmacokinetics of ezogabine suggest first-order kinetics. Tmax, single oral dose = 30-120 minutes; Time to steady state = 3 days
Volume of distribution

8.7 L/kg

Protein bindingApproximately 80% protein bound.
Metabolism

Ezogabine is metabolized exclusively via phase II hepatic N-glucurodination and acetylation. N-glucurodination is the major metabolic pathway of the two and form two major N-glucuronide metabolites. The enzymes involved are UGT1A1, 1A9, 1A4, and 1A3. However, the product of the N-acetyl pathway is a weak, active metabolite referred to as NAMR. The enzyme that is involved in the N-acetyl pathway is called N-acetyltransferase 2. The pharmacokinetics of NAMR and ezogabine are similar. The cytochrome P450 enzyme system is not involved with the metabolism of ezogabine.

Route of eliminationUrine (85%, 36% of total dose as unchanged drug, 18% of total dose as NAMR) and feces (14%, 3% of total dose as unchanged drug)
Half lifeTerminal half-life = 7.5 hours
Clearance

0.58 – 0.76 L/h·kg. Clearance may differ between ethnic groups with Black Americans having 20% lower clearance than Caucasian Americans.

ToxicityLethal Dose, acute, oral, rat = 100 mg/kg; Lethal Dose, chronic, oral, rat = 5.1 mg/kg/day, 90-day; Most common adverse effects that lead to discontinuation of therapy include dizziness and somnolence.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9876
Blood Brain Barrier+0.9382
Caco-2 permeable-0.5245
P-glycoprotein substrateNon-substrate0.5295
P-glycoprotein inhibitor INon-inhibitor0.6642
P-glycoprotein inhibitor IINon-inhibitor0.9155
Renal organic cation transporterNon-inhibitor0.8998
CYP450 2C9 substrateNon-substrate0.8602
CYP450 2D6 substrateNon-substrate0.8045
CYP450 3A4 substrateNon-substrate0.679
CYP450 1A2 substrateInhibitor0.8417
CYP450 2C9 inhibitorNon-inhibitor0.607
CYP450 2D6 inhibitorInhibitor0.5995
CYP450 2C19 inhibitorNon-inhibitor0.5221
CYP450 3A4 inhibitorInhibitor0.5085
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6414
Ames testNon AMES toxic0.5119
CarcinogenicityNon-carcinogens0.621
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.4793 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9807
hERG inhibition (predictor II)Non-inhibitor0.6007
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tablet, film coatedoral200 mg/1
Tablet, film coatedoral300 mg/1
Tablet, film coatedoral400 mg/1
Tablet, film coatedoral50 mg/1
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
pKa10.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0307 mg/mLALOGPS
logP3.07ALOGPS
logP2.7ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)13.6ChemAxon
pKa (Strongest Basic)3.99ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area76.38 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity87.02 m3·mol-1ChemAxon
Polarizability31.97 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Porter RJ, Nohria V, Rundfeldt C: Retigabine. Neurotherapeutics. 2007 Jan;4(1):149-54. [PubMed:17199031 ]
  2. Hermann R, Ferron GM, Erb K, Knebel N, Ruus P, Paul J, Richards L, Cnota HP, Troy S: Effects of age and sex on the disposition of retigabine. Clin Pharmacol Ther. 2003 Jan;73(1):61-70. [PubMed:12545144 ]
  3. Hermann R, Knebel NG, Niebch G, Richards L, Borlak J, Locher M: Pharmacokinetic interaction between retigabine and lamotrigine in healthy subjects. Eur J Clin Pharmacol. 2003 Apr;58(12):795-802. Epub 2003 Feb 28. [PubMed:12698305 ]
  4. Dost R, Rostock A, Rundfeldt C: The anti-hyperalgesic activity of retigabine is mediated by KCNQ potassium channel activation. Naunyn Schmiedebergs Arch Pharmacol. 2004 Apr;369(4):382-90. Epub 2004 Mar 9. [PubMed:15007538 ]
  5. Mikkelsen JD: The KCNQ channel activator retigabine blocks haloperidol-induced c-Fos expression in the striatum of the rat. Neurosci Lett. 2004 May 27;362(3):240-3. [PubMed:15158023 ]
  6. Punke MA, Friederich P: Retigabine stimulates human KCNQ2/Q3 channels in the presence of bupivacaine. Anesthesiology. 2004 Aug;101(2):430-8. [PubMed:15277926 ]
  7. Wuttke TV, Seebohm G, Bail S, Maljevic S, Lerche H: The new anticonvulsant retigabine favors voltage-dependent opening of the Kv7.2 (KCNQ2) channel by binding to its activation gate. Mol Pharmacol. 2005 Apr;67(4):1009-17. Epub 2005 Jan 20. [PubMed:15662042 ]
  8. Fatope MO: Retigabine (ASTA Medica). IDrugs. 2001 Jan;4(1):93-8. [PubMed:16034707 ]
  9. Orhan G, Wuttke TV, Nies AT, Schwab M, Lerche H: Retigabine/Ezogabine, a KCNQ/K(V)7 channel opener: pharmacological and clinical data. Expert Opin Pharmacother. 2012 Aug;13(12):1807-16. doi: 10.1517/14656566.2012.706278. Epub 2012 Jul 12. [PubMed:22783830 ]
  10. Amabile CM, Vasudevan A: Ezogabine: a novel antiepileptic for adjunctive treatment of partial-onset seizures. Pharmacotherapy. 2013 Feb;33(2):187-94. doi: 10.1002/phar.1185. [PubMed:23386597 ]
External Links
ATC CodesN03AX21
AHFS Codes
  • 28:12.92
PDB EntriesNot Available
FDA labelDownload (516 KB)
MSDSDownload (132 KB)
Interactions
Drug Interactions
Drug
AzelastineEzogabine may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
BaclofenThe risk or severity of adverse effects can be increased when Baclofen is combined with Ezogabine.
BrimonidineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
BuprenorphineEzogabine may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.
CarbamazepineThe serum concentration of Ezogabine can be decreased when it is combined with Carbamazepine.
CitalopramEzogabine may increase the QTc-prolonging activities of Citalopram.
DofetilideEzogabine may increase the QTc-prolonging activities of Dofetilide.
DoxylamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
DronabinolDronabinol may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
DroperidolDroperidol may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
EthanolThe risk or severity of adverse effects can be increased when Ethanol is combined with Ezogabine.
FosphenytoinThe serum concentration of Ezogabine can be decreased when it is combined with Fosphenytoin.
GoserelinEzogabine may increase the QTc-prolonging activities of Goserelin.
HydrocodoneEzogabine may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
HydroxyzineHydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
LamotrigineThe serum concentration of Lamotrigine can be decreased when it is combined with Ezogabine.
LeuprolideEzogabine may increase the QTc-prolonging activities of Leuprolide.
LorazepamThe risk or severity of adverse effects can be increased when Lorazepam is combined with Ezogabine.
Magnesium SulfateMagnesium Sulfate may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
MefloquineThe therapeutic efficacy of Ezogabine can be decreased when used in combination with Mefloquine.
MethotrimeprazineEzogabine may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.
MetyrosineEzogabine may increase the sedative activities of Metyrosine.
MianserinThe therapeutic efficacy of Ezogabine can be decreased when used in combination with Mianserin.
MifepristoneMifepristone may increase the QTc-prolonging activities of Ezogabine.
MinocyclineMinocycline may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
MirtazapineEzogabine may increase the central nervous system depressant (CNS depressant) activities of Mirtazapine.
NabiloneNabilone may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
OrlistatThe serum concentration of Ezogabine can be decreased when it is combined with Orlistat.
OrphenadrineEzogabine may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
ParaldehydeEzogabine may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
ParoxetineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Paroxetine.
PerampanelPerampanel may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
PhenytoinThe serum concentration of Ezogabine can be decreased when it is combined with Phenytoin.
PramipexoleEzogabine may increase the sedative activities of Pramipexole.
RopiniroleEzogabine may increase the sedative activities of Ropinirole.
RotigotineEzogabine may increase the sedative activities of Rotigotine.
RufinamideThe risk or severity of adverse effects can be increased when Rufinamide is combined with Ezogabine.
Sodium oxybateSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
SuvorexantEzogabine may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.
TapentadolTapentadol may increase the central nervous system depressant (CNS depressant) activities of Ezogabine.
ThalidomideEzogabine may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
ZolpidemEzogabine may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
Food Interactions
  • With a high-fat meal, Cmax is moderately increased.

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Voltage-gated potassium channel activity
Specific Function:
Probably important in the regulation of neuronal excitability. Associates with KCNQ3 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic in...
Gene Name:
KCNQ2
Uniprot ID:
O43526
Molecular Weight:
95846.575 Da
References
  1. Wuttke TV, Seebohm G, Bail S, Maljevic S, Lerche H: The new anticonvulsant retigabine favors voltage-dependent opening of the Kv7.2 (KCNQ2) channel by binding to its activation gate. Mol Pharmacol. 2005 Apr;67(4):1009-17. Epub 2005 Jan 20. [PubMed:15662042 ]
  2. Hirano K, Kuratani K, Fujiyoshi M, Tashiro N, Hayashi E, Kinoshita M: Kv7.2-7.5 voltage-gated potassium channel (KCNQ2-5) opener, retigabine, reduces capsaicin-induced visceral pain in mice. Neurosci Lett. 2007 Feb 14;413(2):159-62. Epub 2006 Dec 20. [PubMed:17184917 ]
  3. Punke MA, Friederich P: Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels. Anesth Analg. 2007 May;104(5):1256-64, tables of contents. [PubMed:17456683 ]
  4. Main MJ, Cryan JE, Dupere JR, Cox B, Clare JJ, Burbidge SA: Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine. Mol Pharmacol. 2000 Aug;58(2):253-62. [PubMed:10908292 ]
  5. Wickenden AD, Yu W, Zou A, Jegla T, Wagoner PK: Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels. Mol Pharmacol. 2000 Sep;58(3):591-600. [PubMed:10953053 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Voltage-gated potassium channel activity
Specific Function:
Probably important in the regulation of neuronal excitability. Associates with KCNQ2 or KCNQ5 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to sy...
Gene Name:
KCNQ3
Uniprot ID:
O43525
Molecular Weight:
96741.515 Da
References
  1. Hirano K, Kuratani K, Fujiyoshi M, Tashiro N, Hayashi E, Kinoshita M: Kv7.2-7.5 voltage-gated potassium channel (KCNQ2-5) opener, retigabine, reduces capsaicin-induced visceral pain in mice. Neurosci Lett. 2007 Feb 14;413(2):159-62. Epub 2006 Dec 20. [PubMed:17184917 ]
  2. Punke MA, Friederich P: Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels. Anesth Analg. 2007 May;104(5):1256-64, tables of contents. [PubMed:17456683 ]
  3. Main MJ, Cryan JE, Dupere JR, Cox B, Clare JJ, Burbidge SA: Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine. Mol Pharmacol. 2000 Aug;58(2):253-62. [PubMed:10908292 ]
  4. Wickenden AD, Yu W, Zou A, Jegla T, Wagoner PK: Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels. Mol Pharmacol. 2000 Sep;58(3):591-600. [PubMed:10953053 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Potassium channel activity
Specific Function:
Probably important in the regulation of neuronal excitability. May underlie a potassium current involved in regulating the excitability of sensory cells of the cochlea. KCNQ4 channels are blocked by linopirdin, XE991 and bepridil, whereas clofilium is without significant effect. Muscarinic agonist oxotremorine-M strongly suppress KCNQ4 current in CHO cells in which cloned KCNQ4 channels were co...
Gene Name:
KCNQ4
Uniprot ID:
P56696
Molecular Weight:
77099.99 Da
References
  1. Hirano K, Kuratani K, Fujiyoshi M, Tashiro N, Hayashi E, Kinoshita M: Kv7.2-7.5 voltage-gated potassium channel (KCNQ2-5) opener, retigabine, reduces capsaicin-induced visceral pain in mice. Neurosci Lett. 2007 Feb 14;413(2):159-62. Epub 2006 Dec 20. [PubMed:17184917 ]
  2. Schroder RL, Jespersen T, Christophersen P, Strobaek D, Jensen BS, Olesen SP: KCNQ4 channel activation by BMS-204352 and retigabine. Neuropharmacology. 2001 Jun;40(7):888-98. [PubMed:11378159 ]
  3. Borlak J, Gasparic A, Locher M, Schupke H, Hermann R: 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. [PubMed:16713428 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Voltage-gated potassium channel activity
Specific Function:
Probably important in the regulation of neuronal excitability. Associates with KCNQ3 to form a potassium channel which contributes to M-type current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons. May contribute, with other potassium channels, to the molecular diversity of a heterogeneous...
Gene Name:
KCNQ5
Uniprot ID:
Q9NR82
Molecular Weight:
102178.015 Da
References
  1. Hirano K, Kuratani K, Fujiyoshi M, Tashiro N, Hayashi E, Kinoshita M: Kv7.2-7.5 voltage-gated potassium channel (KCNQ2-5) opener, retigabine, reduces capsaicin-induced visceral pain in mice. Neurosci Lett. 2007 Feb 14;413(2):159-62. Epub 2006 Dec 20. [PubMed:17184917 ]
  2. Hermann R, Ferron GM, Erb K, Knebel N, Ruus P, Paul J, Richards L, Cnota HP, Troy S: Effects of age and sex on the disposition of retigabine. Clin Pharmacol Ther. 2003 Jan;73(1):61-70. [PubMed:12545144 ]
  3. Borlak J, Gasparic A, Locher M, Schupke H, Hermann R: 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. [PubMed:16713428 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid binding
Specific Function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naph...
Gene Name:
UGT1A1
Uniprot ID:
P22309
Molecular Weight:
59590.91 Da
References
  1. Hiller A, Nguyen N, Strassburg CP, Li Q, Jainta H, Pechstein B, Ruus P, Engel J, Tukey RH, Kronbach T: Retigabine N-glucuronidation and its potential role in enterohepatic circulation. Drug Metab Dispos. 1999 May;27(5):605-12. [PubMed:10220490 ]
  2. Borlak J, Gasparic A, Locher M, Schupke H, Hermann R: 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. [PubMed:16713428 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Retinoic acid binding
Specific Function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1.
Gene Name:
UGT1A3
Uniprot ID:
P35503
Molecular Weight:
60337.835 Da
References
  1. Hiller A, Nguyen N, Strassburg CP, Li Q, Jainta H, Pechstein B, Ruus P, Engel J, Tukey RH, Kronbach T: Retigabine N-glucuronidation and its potential role in enterohepatic circulation. Drug Metab Dispos. 1999 May;27(5):605-12. [PubMed:10220490 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Protein homodimerization activity
Specific Function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1 (By similarity).
Gene Name:
UGT1A4
Uniprot ID:
P22310
Molecular Weight:
60024.535 Da
References
  1. Hiller A, Nguyen N, Strassburg CP, Li Q, Jainta H, Pechstein B, Ruus P, Engel J, Tukey RH, Kronbach T: Retigabine N-glucuronidation and its potential role in enterohepatic circulation. Drug Metab Dispos. 1999 May;27(5):605-12. [PubMed:10220490 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Retinoic acid binding
Specific Function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1.
Gene Name:
UGT1A9
Uniprot ID:
O60656
Molecular Weight:
59940.495 Da
References
  1. Hiller A, Nguyen N, Strassburg CP, Li Q, Jainta H, Pechstein B, Ruus P, Engel J, Tukey RH, Kronbach T: Retigabine N-glucuronidation and its potential role in enterohepatic circulation. Drug Metab Dispos. 1999 May;27(5):605-12. [PubMed:10220490 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity.
Gene Name:
CYP2A6
Uniprot ID:
P11509
Molecular Weight:
56501.005 Da
References
  1. Orhan G, Wuttke TV, Nies AT, Schwab M, Lerche H: Retigabine/Ezogabine, a KCNQ/K(V)7 channel opener: pharmacological and clinical data. Expert Opin Pharmacother. 2012 Aug;13(12):1807-16. doi: 10.1517/14656566.2012.706278. Epub 2012 Jul 12. [PubMed:22783830 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Arylamine n-acetyltransferase activity
Specific Function:
Participates in the detoxification of a plethora of hydrazine and arylamine drugs. Catalyzes the N- or O-acetylation of various arylamine and heterocyclic amine substrates and is able to bioactivate several known carcinogens.
Gene Name:
NAT2
Uniprot ID:
P11245
Molecular Weight:
33542.235 Da
References
  1. Amabile CM, Vasudevan A: Ezogabine: a novel antiepileptic for adjunctive treatment of partial-onset seizures. Pharmacotherapy. 2013 Feb;33(2):187-94. doi: 10.1002/phar.1185. [PubMed:23386597 ]
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Drug created on October 21, 2007 16:23 / Updated on September 16, 2013 17:26