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

Stem definition	Drug id	CAS RN
gabamimetic agents	2648	115103-54-3

Description:

Molecule	Description
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

Molecule

Description

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:

Dose	Unit	Route
30	mg	O

ADMET properties:

Property	Value	Reference
MRTD (Maximum Recommended Therapeutic Daily Dose)	2.85 µM/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:

Date	Agency	Company	Orphan
Sept. 30, 1997	FDA	CEPHALON

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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 term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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:

Source	Code	Description
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)

Disease	Relation	SNOMED_ID	DOID
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 level	Dissociation constant	Type (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:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Sodium- and chloride-dependent GABA transporter 1	Transporter	P30531	SC6A1_HUMAN	INHIBITOR	Ki	7.77	CHEMBL	CHEMBL
Sodium- and chloride-dependent GABA transporter 1	Transporter		SC6A1_RAT		Ki	7.17	CHEMBL
Sodium- and chloride-dependent GABA transporter 1	Transporter		SC6A1_MOUSE		Ki	7.41	CHEMBL
Sodium- and chloride-dependent betaine transporter	Unclassified		S6A12_MOUSE		IC50	6.74	CHEMBL

External reference:

ID	Source
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:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
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