retigabine 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
gabamimetic agents 4181 150812-12-7

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • D-20443
  • trobalt
  • ezogabine
  • potiga
  • KE 841
  • GW 582892X
  • WAY 143841
  • retigabine
It is a first-in-class anticonvulsant that works by activating KCNQ2/3 channels. 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.
  • Molecular weight: 303.34
  • Formula: C16H18FN3O2
  • CLOGP: 2
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 3
  • TPSA: 76.38
  • ALOGS: -3.99
  • ROTB: 6
  • Status: OFM
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.90 g O

ADMET properties:

PropertyValueReference
Vd (Volume of distribution) 2.50 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 8.30 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.20 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 9 hours Lombardo F, Berellini G, Obach RS
BA (Bioavailability) 60 %

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 2.200 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.558 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 56.624 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 6.577 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 13.570 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 32.720 % High 1
herg hERG pIC50 4.650 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 3.926 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 4.764 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 15.730 % High 1
kinase-safety-class ACVR2A,ACVR2B,AKT2,AKT3,ALK,AURKA,AURKB,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK1,CDK4,CDK5,CDK9,CHEK1,DDR1,DYRK1B,EIF2AK3,EPHB4,ERBB2,FGFR1,FLT3,GRK1,GRK2,GRK3,GSK3B,ITK,JAK1,JAK2,KIT,MAP2K6,MAP3K1,MAP3K10,MAP3K11,MAP3K14,MAP3K21,MAP3K7,MAP4K1,MAP4K3,MAPK1,MAPK10,MAPK12,MAPK7,MAPK9,MAPKAPK2,MAPKAPK5,MARK4,MELK,MET,MTOR,NTRK2,PAK4,PDK2,PDK4,PDPK1,PIK3CB,PIK3CD,PIM2,PLK1,PRKCD,PRKDC,SGK1,SIK2,SIK3,STK33,SYK,TEK,TTK,ULK1,ULK2 72
kinase-selectivity-class AXL,DDR1,EPHB4,ERBB2,GRK2,MAP2K6,MAPK7,PDK4,STK33,TEK,TTK 11
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 1.030 High 1
mh-clint Mouse hepatocyte intrinsic clearance 26.546 High 1
mppb Mouse plasma protein binding (% unbound) 11.740 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 2.541 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 35.520 % High 1
rh-clint Rat hepatocyte intrinsic clearance 31.117 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 71.570 % High 1
rppb Rat plasma protein binding (% unbound) 15.820 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 102.094 uM High 1

Approvals:

DateAgencyCompanyOrphan
March 28, 2011 EMA
June 10, 2011 FDA GLAXOSMITHKLINE

FDA Adverse Event Reporting System (Female)

None

FDA Adverse Event Reporting System (Male)

None

FDA Adverse Event Reporting System (Geriatric)

None

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC N03AX21 NERVOUS SYSTEM
ANTIEPILEPTICS
ANTIEPILEPTICS
Other antiepileptics
MeSH PA D000927 Anticonvulsants
MeSH PA D002491 Central Nervous System Agents
MeSH PA D049990 Membrane Transport Modulators
FDA MoA N0000182728 Potassium Channel Openers
FDA EPC N0000182729 Potassium Channel Opener
CHEBI has role CHEBI:35469 antidepressant
CHEBI has role CHEBI:35623 anticonvulsant
CHEBI has role CHEBI:50510 potassium channel modulator

Related Drugs by ATC class:

N03AX Other antiepileptics 18 drugs
beclamidebrivaracetamcannabidiolcarisbamatecenobamatefelbamatefenfluramineganaxolonelacosamidelamotriginelevetiracetamperampanel show all 18 →

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Partial Epilepsy Treatment Adjunct indication




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 10.53 acidic
pKa2 4.74 Basic
pKa3 3.12 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Potassium voltage-gated channel subfamily KQT member 2 Ion channel ACTIVATOR EC50 5.60 IUPHAR CHEMBL
Potassium voltage-gated channel subfamily KQT member 3 Ion channel ACTIVATOR EC50 6.20 IUPHAR CHEMBL
Potassium voltage-gated channel subfamily KQT member 5 Ion channel ACTIVATOR EC50 5 IUPHAR CHEMBL
Potassium voltage-gated channel subfamily KQT member 4 Ion channel ACTIVATOR EC50 5.20 IUPHAR CHEMBL
Potassium voltage-gated channel subfamily KQT member 2 Ion channel EC50 5.89 CHEMBL

External reference:

IDSource
4030907 VUID
N0000182972 NUI
D09569 KEGG_DRUG
4030907 VANDF
C0530684 UMLSCUI
CHEBI:68584 CHEBI
CHEMBL41355 ChEMBL_ID
DB04953 DRUGBANK_ID
C101866 MESH_SUPPLEMENTAL_RECORD_UI
2601 IUPHAR_LIGAND_ID
121892 PUBCHEM_CID
1112990 RXNORM
184560 MMSL
27995 MMSL
d07769 MMSL
013807 NDDF
699271005 SNOMEDCT_US
704476003 SNOMEDCT_US
FBX PDB_CHEM_ID
7545 INN_ID
12G01I6BBU UNII

Pharmaceutical products:

None