Tiagabine

Summary

Tiagabine (CHEMBL1027) is an approved small-molecule GABA reuptake inhibitor (ATC N03AG06) targeting SLC6A1; indicated across 6 conditions including epilepsy and anxiety.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N03AG06
• Targets: 1 (SLC6A1)
• Indications: 6 conditions
• Clinical trials: 12
• Chemistry: 375.6 Da · C20H25NO2S2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1027
Name	Tiagabine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	60648
ChEBI	CHEBI:9586
ATC	N03AG06
Molecular formula	C20H25NO2S2
Molecular weight	375.6
InChIKey	PBJUNZJWGZTSKL-MRXNPFEDSA-N

SMILES: CC1=C(SC=C1)C(=CCCN2CCC[C@H](C2)C(=O)O)C3=C(C=CS3)C

IUPAC name: (3R)-1-[4,4-bis(3-methylthiophen-2-yl)but-3-enyl]piperidine-3-carboxylic acid

ChEBI definition: A piperidinemonocarboxylic acid that is (R)-nipecotic acid in which the hydrogen attached to the nitrogen has been replaced by a 1,1-bis(3-methyl-2-thienyl)but-1-en-4-yl group. A GABA reuptake inhibitor, it is used (generally as the hydrochloride salt) for the treatment of epilepsy.

Pharmacological roles (ChEBI): GABA reuptake inhibitor, anticonvulsant.

Also known as: ABBOTT-70569 FREE BASE, ABBOTT-705691 FREE BASE, ABT-569 FREE BASE, Gabitril, NNC-050328 FREE BASE, NO-050328 FREE BASE, Tiagabina, Tiagabine, tiagabine, SID26758048, Tiagabine(R), TIAGABINE

Parent form; salt/anhydrous children: CHEMBL1695

Patent coverage: 3,029 distinct patent families (12,112 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
SLC6A1	GAT1	Inhibition		0.2%	P30531

Broader ChEMBL bioactivity targets: 6 (assay-derived). Sample: Sodium- and chloride-dependent GABA transporter 1, Prostaglandin G/H synthase 1, 3’,5’-cyclic-AMP phosphodiesterase 4A, Sodium- and chloride-dependent GABA transporter 1, GABA transporter 2, Sodium- and chloride-dependent GABA transporter 1.

Bioactivity

ChEMBL activities: 54 potent at pChembl ≥ 5 of 56 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
SLC6A1	7.77	Ki	16.98	nM	CHEMBL_ACT_5136748
P31648	7.56	Ki	27.54	nM	CHEMBL_ACT_19115879
P31648	7.43	Ki	37.15	nM	CHEMBL_ACT_15161670
P31648	7.43	Ki	37.15	nM	CHEMBL_ACT_16505485
P31648	7.43	Ki	37.15	nM	CHEMBL_ACT_18302977
P31648	7.43	Ki	37.15	nM	CHEMBL_ACT_18995535
P31648	7.43	Ki	37.15	nM	CHEMBL_ACT_19304631
P31648	7.43	IC50	37.15	nM	CHEMBL_ACT_23287407
P31648	7.43	Ki	37.15	nM	CHEMBL_ACT_24726285
P31648	7.41	Ki	38.9	nM	CHEMBL_ACT_13405230
SLC6A1	7.39	Kd	40.5	nM	CHEMBL_ACT_19115914
SLC6A1	7.32	Ki	47.86	nM	CHEMBL_ACT_15161669
P31648	7.26	Ki	54.95	nM	CHEMBL_ACT_19251176
P31648	7.2	IC50	63.1	nM	CHEMBL_ACT_12617940
P31648	7.16	IC50	70	nM	CHEMBL_ACT_12617945
P23978	7.16	IC50	70	nM	CHEMBL_ACT_15225728
P23978	7.16	IC50	70	nM	CHEMBL_ACT_19251175
SLC6A1	7.16	IC50	70	nM	CHEMBL_ACT_858698
P31648	6.88	IC50	131.8	nM	CHEMBL_ACT_13316794
P31648	6.88	IC50	131.8	nM	CHEMBL_ACT_13405916
P31648	6.88	IC50	131.8	nM	CHEMBL_ACT_15161667
P31648	6.88	IC50	131.8	nM	CHEMBL_ACT_16846280
P31648	6.88	IC50	131.8	nM	CHEMBL_ACT_18302978
P31648	6.88	IC50	131.8	nM	CHEMBL_ACT_18337047
P31648	6.88	IC50	131.8	nM	CHEMBL_ACT_18995357
P31648	6.88	IC50	131.8	nM	CHEMBL_ACT_19115885
P31648	6.88	IC50	131.8	nM	CHEMBL_ACT_19304614
P31648	6.88	IC50	131.8	nM	CHEMBL_ACT_23287242
P31648	6.88	IC50	131.8	nM	CHEMBL_ACT_24726281
P31648	6.88	IC50	131.8	nM	CHEMBL_ACT_2507542
SLC6A1	6.83	Kd	146.8	nM	CHEMBL_ACT_19115916
SLC6A1	6.81	IC50	154.9	nM	CHEMBL_ACT_19115937
P31651	6.75	IC50	180	nM	CHEMBL_ACT_12663638
P31648	6.72	IC50	191	nM	CHEMBL_ACT_3062579
SLC6A1	6.55	IC50	280	nM	CHEMBL_ACT_1664496
P31651	6.44	IC50	360	nM	CHEMBL_ACT_12663625
SLC6A1	6.42	IC50	380.2	nM	CHEMBL_ACT_15161668
P23978	6.19	IC50	640	nM	CHEMBL_ACT_15225735
P31648	6.1	IC50	800	nM	CHEMBL_ACT_12663612
P31648	6.1	IC50	800	nM	CHEMBL_ACT_15179851
P23978	5.77	IC50	1710	nM	CHEMBL_ACT_1476013
P23978	5.75	IC50	1780	nM	CHEMBL_ACT_1476008
P23978	5.75	IC50	1790	nM	CHEMBL_ACT_1476012
P23978	5.73	IC50	1870	nM	CHEMBL_ACT_1476019
P23978	5.67	IC50	2140	nM	CHEMBL_ACT_1476010
P23978	5.67	IC50	2130	nM	CHEMBL_ACT_1476015
P23978	5.67	IC50	2120	nM	CHEMBL_ACT_1476017
P23978	5.6	IC50	2500	nM	CHEMBL_ACT_1475901
P23978	5.6	IC50	2520	nM	CHEMBL_ACT_1476014
P23978	5.57	IC50	2680	nM	CHEMBL_ACT_1476011
P23978	5.57	IC50	2720	nM	CHEMBL_ACT_1476020
P23978	5.56	IC50	2760	nM	CHEMBL_ACT_1476018
P23978	5.54	IC50	2920	nM	CHEMBL_ACT_1476009
P23978	5.54	IC50	2880	nM	CHEMBL_ACT_1476016

Target pathways

Aggregated over 1 target gene(s): SLC6A1.

Top Reactome pathways

9 total, by targets touching each:

Pathway	Targets	Genes
Neurotransmitter release cycle	1	SLC6A1
Transmission across Chemical Synapses	1	SLC6A1
Neuronal System	1	SLC6A1
Transport of small molecules	1	SLC6A1
R-HSA-425366	1	SLC6A1
SLC-mediated transmembrane transport	1	SLC6A1
SLC-mediated transport of neurotransmitters	1	SLC6A1
GABA synthesis, release, reuptake and degradation	1	SLC6A1
Reuptake of GABA	1	SLC6A1

Dominant GO biological processes

GO term	Targets
amino acid transport	1
chemical synaptic transmission	1
memory	1
associative learning	1
sodium ion transmembrane transport	1
synapse organization	1
gamma-aminobutyric acid reuptake	1
gamma-aminobutyric acid import	1
inorganic anion import across plasma membrane	1
sodium ion import across plasma membrane	1
transport across blood-brain barrier	1
chloride transmembrane transport	1
amino acid transmembrane transport	1
neurotransmitter transport	1
gamma-aminobutyric acid transport	1

Indications & clinical

Indications

1 approved indication. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
epilepsy	4	MONDO:0005027	EFO:0000474

4 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
anxiety	3	MONDO:0011918	EFO:0005230
obstructive sleep apnea syndrome	2	MONDO:0007147	EFO:0003918
cocaine dependence	2	MONDO:0005186	EFO:0002610
alcohol abuse	1	MONDO:0002046	MONDO:0007079

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 12.

Phase distribution

Phase	Trials
PHASE3	5
PHASE2	3
PHASE4	2
PHASE1	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00208741	PHASE4	COMPLETED	Study To Evaluate The Effects Of Gabitril™ In Patients With Social Anxiety Disorder
NCT00855738	PHASE4	COMPLETED	A Prospective, Observational Study On The Effectiveness Of New Antiepileptic Drugs As First Bitherapy In The Daily Clinical Practice
NCT00179465	PHASE3	ACTIVE_NOT_RECRUITING	Treating Schizophrenia by Correcting Abnormal Brain Development
NCT00214994	PHASE3	COMPLETED	Study to Evaluate the Safety and Efficacy of GABITRIL Treatment in Adults With Generalized Anxiety Disorder.
NCT00236015	PHASE3	COMPLETED	A 10-Week Efficacy and Safety Study of Gabitril in the Treatment of Adults With Generalized Anxiety Disorder
NCT00236054	PHASE3	COMPLETED	A 10-Week Efficacy and Safety Study for of Gabitril in the Treatment of Adults With Generalized Anxiety Disorder
NCT00236067	PHASE3	COMPLETED	A 10-Week Study for Efficacy and Safety Study of Gabitril in the Treatment of Adults With Generalized Anxiety Disorder
NCT00086255	PHASE2	COMPLETED	Tiagabine for the Treatment of Cocaine Dependence - 1
NCT00129298	PHASE2	COMPLETED	Effectiveness of Tiagabine for Cocaine Dependence in Methadone-Maintained Individuals - 1
NCT02387710	PHASE2	COMPLETED	Tiagabine to Enhance Slow Wave Sleep in Patients With Sleep Apnea
NCT01904487	PHASE1	COMPLETED	Characterization of [11C]Flumazenil to Image GABA Transmission in Healthy Adult Subjects and Subjects With Alcohol Dependence
NCT03196466	Not specified	COMPLETED	Population Pharmacokinetics of Antiepileptic in Pediatrics

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

1 molecules share ≥1 primary target. Top 1 by shared-target count:

Molecule	Source	Status	Shared targets
.gamma.-aminobutyric acid	PubChem	Approved	SLC6A1