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Namespace Prefixes

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Statements

Subject Item
n2:DB04953
rdf:type
n3:Drug
n3: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.
n3:dosage
n17:271B60EF-363D-11E5-9242-09173F13E4C5 n17:271B60F0-363D-11E5-9242-09173F13E4C5 n17:271B60F1-363D-11E5-9242-09173F13E4C5 n17:271B60F2-363D-11E5-9242-09173F13E4C5
n3:generalReferences
# Porter RJ, Nohria V, Rundfeldt C: Retigabine. Neurotherapeutics. 2007 Jan;4(1):149-54. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/17199031 # 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":http://www.ncbi.nlm.nih.gov/pubmed/12545144 # 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":http://www.ncbi.nlm.nih.gov/pubmed/12698305 # 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":http://www.ncbi.nlm.nih.gov/pubmed/15007538 # 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":http://www.ncbi.nlm.nih.gov/pubmed/15158023 # Punke MA, Friederich P: Retigabine stimulates human KCNQ2/Q3 channels in the presence of bupivacaine. Anesthesiology. 2004 Aug;101(2):430-8. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/15277926 # 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":http://www.ncbi.nlm.nih.gov/pubmed/15662042 # Fatope MO: Retigabine (ASTA Medica). IDrugs. 2001 Jan;4(1):93-8. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/16034707 # 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":http://www.ncbi.nlm.nih.gov/pubmed/22783830 # 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":http://www.ncbi.nlm.nih.gov/pubmed/23386597
n3:group
approved
n3:halfLife
Terminal half-life = 7.5 hours
n3:indication
Adjuvant treatment of partial-onset seizures.
owl:sameAs
n6:DB04953
dcterms:title
Ezogabine
adms:identifier
n13:10239851 n14:Retigabine n15:PA144997862 n16:121892 n20:68584 n21:108740 n22:50143558 n23:D09569 n24:0173-0814-59 n25:DB04953 n26:C13826
n3:mechanismOfAction
Ezogabine 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.
n3:routeOfElimination
Urine (85%, 36% of total dose as unchanged drug, 18% of total dose as NAMR) and feces (14%, 3% of total dose as unchanged drug)
n3:synonym
RTG Potiga N-(2-Amino-4-(4-fluorobenzylamino)-phenyl) carbamic acid ethyl ester N-(2-Amino-4-(4-fluorobenzylamino)phenyl)carbamic acid ethyl ester D-23129 Retigabine Ethyl 2-amino-4-((P-fluorobenzyl)amino)carbanilate EZG Ethyl {2-amino-4-[(4-fluorobenzyl)amino]phenyl}carbamate
n3:toxicity
Lethal 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.
n3:volumeOfDistribution
8.7 L/kg
n9:hasAHFSCode
n10:28-12-92%20
n3:foodInteraction
With a high-fat meal, Cmax is moderately increased.
n3:proteinBinding
Approximately 80% protein bound.
foaf:page
n8:ezogabine.html n11:potiga-drug.htm
n3:IUPAC-Name
n4:271B60F7-363D-11E5-9242-09173F13E4C5
n3:InChI
n4:271B60FD-363D-11E5-9242-09173F13E4C5
n3:Molecular-Formula
n4:271B60FC-363D-11E5-9242-09173F13E4C5
n3:Molecular-Weight
n4:271B60F9-363D-11E5-9242-09173F13E4C5
n3:Monoisotopic-Weight
n4:271B60FA-363D-11E5-9242-09173F13E4C5
n3:SMILES
n4:271B60FB-363D-11E5-9242-09173F13E4C5
n3:Water-Solubility
n4:271B60F5-363D-11E5-9242-09173F13E4C5
n3:logP
n4:271B60F3-363D-11E5-9242-09173F13E4C5 n4:271B60F6-363D-11E5-9242-09173F13E4C5
n3:logS
n4:271B60F4-363D-11E5-9242-09173F13E4C5
n3:pKa
n4:271B610D-363D-11E5-9242-09173F13E4C5
n9:hasATCCode
n18:N03AX21
n3:H-Bond-Acceptor-Count
n4:271B6103-363D-11E5-9242-09173F13E4C5
n3:H-Bond-Donor-Count
n4:271B6104-363D-11E5-9242-09173F13E4C5
n3:InChIKey
n4:271B60FE-363D-11E5-9242-09173F13E4C5
n3:Polar-Surface-Area--PSA-
n4:271B60FF-363D-11E5-9242-09173F13E4C5
n3:Polarizability
n4:271B6101-363D-11E5-9242-09173F13E4C5
n3:Refractivity
n4:271B6100-363D-11E5-9242-09173F13E4C5
n3:Rotatable-Bond-Count
n4:271B6102-363D-11E5-9242-09173F13E4C5
n3:absorption
Rapidly 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
n3:affectedOrganism
Humans and other mammals
n3:casRegistryNumber
150812-12-7
n3:category
n3:clearance
0.58 - 0.76 L/h·kg. Clearance may differ between ethnic groups with Black Americans having 20% lower clearance than Caucasian Americans.
n3:Bioavailability
n4:271B6109-363D-11E5-9242-09173F13E4C5
n3:Ghose-Filter
n4:271B610B-363D-11E5-9242-09173F13E4C5
n3:MDDR-Like-Rule
n4:271B610C-363D-11E5-9242-09173F13E4C5
n3:Number-of-Rings
n4:271B6108-363D-11E5-9242-09173F13E4C5
n3:Physiological-Charge
n4:271B6107-363D-11E5-9242-09173F13E4C5
n3:Rule-of-Five
n4:271B610A-363D-11E5-9242-09173F13E4C5
n3:Traditional-IUPAC-Name
n4:271B60F8-363D-11E5-9242-09173F13E4C5
n3:pKa--strongest-acidic-
n4:271B6105-363D-11E5-9242-09173F13E4C5
n3:pKa--strongest-basic-
n4:271B6106-363D-11E5-9242-09173F13E4C5