tiagabine Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
gabamimetic agents 2648 115103-54-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • tiagabine
  • (R)-Tiagabine
  • gabatril
  • tiagabine hydrochloride
  • tiagabine HCl
The precise mechanism by which tiagabine exerts its antiseizure effect is unknown, although it is believed to be related to its ability to block GABA uptake into presynaptic neurons, permitting more GABA to be available for receptor binding on the surfaces of post-synaptic cells.
  • Molecular weight: 375.55
  • Formula: C20H25NO2S2
  • CLOGP: 2.78
  • LIPINSKI: 0
  • HAC: 3
  • HDO: 1
  • TPSA: 40.54
  • ALOGS: -4.25
  • ROTB: 6

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
30 mg O

ADMET properties:

PropertyValueReference
MRTD (Maximum Recommended Therapeutic Daily Dose) 2.85 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Hosey CM, Chan R, Benet LZ
S (Water solubility) 0.03 mg/mL Hosey CM, Chan R, Benet LZ
EoM (Fraction excreted unchanged in urine) 2 % Hosey CM, Chan R, Benet LZ
BA (Bioavailability) 90 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 1.10 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 1.60 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.04 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 10 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Sept. 30, 1997 FDA CEPHALON

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Seizure 175.66 27.03 85 1533 122969 46561475
Epilepsy 35.39 27.03 17 1601 23721 46660723
Serotonin syndrome 35.06 27.03 17 1601 24203 46660241
Status epilepticus 33.63 27.03 14 1604 13965 46670479
Focal dyscognitive seizures 31.80 27.03 9 1609 2819 46681625
Confusional state 31.66 27.03 33 1585 159859 46524585
Tremor 30.62 27.03 28 1590 115611 46568833
Generalised tonic-clonic seizure 27.55 27.03 15 1603 27107 46657337

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Seizure 84.02 36.27 47 915 98428 29853088
Status epilepticus 77.74 36.27 24 938 11048 29940468
Generalised tonic-clonic seizure 60.71 36.27 23 939 19528 29931988
Completed suicide 47.71 36.27 33 929 99459 29852057
Drug withdrawal convulsions 40.47 36.27 9 953 1150 29950366

Pharmacologic Action:

SourceCodeDescription
ATC N03AG06 NERVOUS SYSTEM
ANTIEPILEPTICS
ANTIEPILEPTICS
Fatty acid derivatives
FDA PE N0000008486 Decreased Central Nervous System Disorganized Electrical Activity
FDA EPC N0000175753 Anti-epileptic Agent
MeSH PA D000927 Anticonvulsants
MeSH PA D002491 Central Nervous System Agents
MeSH PA D018682 GABA Agents
MeSH PA D058805 GABA Uptake Inhibitors
MeSH PA D049990 Membrane Transport Modulators
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D014179 Neurotransmitter Uptake Inhibitors
CHEBI has role CHEBI:35623 antiepileptic
CHEBI has role CHEBI:85384 gamma-aminobutyric acid re-uptake inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Epilepsy characterized by intractable complex partial seizures indication 442481002
Simple partial seizure indication 117891000119100
Suicidal thoughts contraindication 6471006
Depressive disorder contraindication 35489007
Disease of liver contraindication 235856003 DOID:409

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 3.31 acidic
pKa2 8.82 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
Sodium- and chloride-dependent GABA transporter 1 Transporter INHIBITOR Ki 7.77 CHEMBL CHEMBL
Sodium- and chloride-dependent GABA transporter 1 Transporter Ki 7.17 CHEMBL
Sodium- and chloride-dependent GABA transporter 1 Transporter Ki 7.41 CHEMBL
Sodium- and chloride-dependent betaine transporter Unclassified IC50 6.74 CHEMBL

External reference:

IDSource
4024093 VUID
N0000022098 NUI
D02097 KEGG_DRUG
145821-59-6 SECONDARY_CAS_RN
4021068 VANDF
4024093 VANDF
C0068897 UMLSCUI
CHEBI:9586 CHEBI
60648 PUBCHEM_CID
CHEMBL1027 ChEMBL_ID
CHEMBL1695 ChEMBL_ID
D000078308 MESH_DESCRIPTOR_UI
6306 INN_ID
DB00906 DRUGBANK_ID
Z80I64HMNP UNII
4818 IUPHAR_LIGAND_ID
236875 RXNORM
53205 MMSL
5580 MMSL
d04221 MMSL
007057 NDDF
007058 NDDF
108403006 SNOMEDCT_US
108404000 SNOMEDCT_US
372485004 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Tiagabine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0093-5030 TABLET, FILM COATED 2 mg ORAL NDA AUTHORIZED GENERIC 27 sections
Tiagabine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0093-5031 TABLET, FILM COATED 4 mg ORAL NDA AUTHORIZED GENERIC 27 sections
Tiagabine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0093-8072 TABLET, FILM COATED 12 mg ORAL NDA AUTHORIZED GENERIC 27 sections
Tiagabine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0093-8076 TABLET, FILM COATED 16 mg ORAL NDA AUTHORIZED GENERIC 27 sections
GABITRIL HUMAN PRESCRIPTION DRUG LABEL 1 16590-832 TABLET 12 mg ORAL NDA 16 sections
tiagabine hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 52536-350 TABLET 2 mg ORAL ANDA 29 sections
tiagabine hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 52536-355 TABLET 4 mg ORAL ANDA 29 sections
tiagabine hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 52536-360 TABLET 12 mg ORAL ANDA 29 sections
tiagabine hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 52536-365 TABLET 16 mg ORAL ANDA 29 sections
TIAGABINE HYDROCHLORIDE Human Prescription Drug Label 1 62756-200 TABLET, FILM COATED 2 mg ORAL ANDA 25 sections
TIAGABINE HYDROCHLORIDE Human Prescription Drug Label 1 62756-224 TABLET, FILM COATED 4 mg ORAL ANDA 25 sections
GABITRIL HUMAN PRESCRIPTION DRUG LABEL 1 63459-402 TABLET, FILM COATED 2 mg ORAL NDA 26 sections
GABITRIL HUMAN PRESCRIPTION DRUG LABEL 1 63459-404 TABLET, FILM COATED 4 mg ORAL NDA 26 sections
GABITRIL HUMAN PRESCRIPTION DRUG LABEL 1 63459-412 TABLET, FILM COATED 12 mg ORAL NDA 26 sections
GABITRIL HUMAN PRESCRIPTION DRUG LABEL 1 63459-416 TABLET, FILM COATED 16 mg ORAL NDA 26 sections
GABITRIL HUMAN PRESCRIPTION DRUG LABEL 1 68151-4235 TABLET, FILM COATED 4 mg ORAL NDA 26 sections
Tiagabine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 69238-1104 TABLET 2 mg ORAL ANDA 25 sections
Tiagabine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 69238-1105 TABLET 4 mg ORAL ANDA 25 sections
Tiagabine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 69238-1106 TABLET 12 mg ORAL ANDA 25 sections
Tiagabine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 69238-1107 TABLET 16 mg ORAL ANDA 25 sections