TIAGABINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H25NO2S2
Molecular Weight	375.548
Optical Activity	( - )
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=PBJUNZJWGZTSKL-MRXNPFEDSA-N

InChI=1S/C20H25NO2S2/c1-14-7-11-24-18(14)17(19-15(2)8-12-25-19)6-4-10-21-9-3-5-16(13-21)20(22)23/h6-8,11-12,16H,3-5,9-10,13H2,1-2H3,(H,22,23)/t16-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C20H25NO2S2
Molecular Weight	375.548
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020646s021lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.drugs.com/pro/tiagabine.html | https://www.drugbank.ca/drugs/DB00906 | http://reference.medscape.com/drug/gabitril-tiagabine-343022 | https://www.ncbi.nlm.nih.gov/pubmed/8595791 | https://www.ncbi.nlm.nih.gov/pubmed/16420077 | https://www.ncbi.nlm.nih.gov/pubmed/15519917

Tiagabine (trade name Gabitril) is an anticonvulsant medication used in the treatment of Partial Seizures. The precise mechanism by which Tiagabine exerts its antiseizure effect is unknown, although it is believed to be related to its ability to enhance the activity of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Tiagabine binds to recognition sites associated with the GABA uptake carrier. It is thought that, by this action, Tiagabine blocks GABA uptake into presynaptic neurons, permitting more GABA to be available for receptor binding on the surfaces of post-synaptic cells. Tiagabine is approved by U.S. Food and Drug Administration (FDA) as an adjunctive treatment for partial seizures in individuals of age 12 and up. It may also be prescribed off-label by physicians to treat anxiety disorders and panic disorder as well as neuropathic pain (including fibromyalgia). For anxiety and neuropathic pain, tiagabine is used primarily to augment other treatments. Tiagabine may be used alongside selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, or benzodiazepines for anxiety, or antidepressants, gabapentin, other anticonvulsants, or opioids for neuropathic pain. The most common side effect of tiagabine is dizziness. Other side effects that have been observed with a rate of statistical significance relative to placebo include asthenia, somnolence, nervousness, memory impairment, tremor, headache, diarrhea, and depression.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
GABA transporter 1 8 Target ID: CHEMBL1903 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8057281	Inhibitor 8297	70.0 nM [IC50]
GABA transporter 3 6 Target ID: CHEMBL5208 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8057281	Inhibitor 8297	917.0 µM [IC50]
Betaine transporter 4 Target ID: CHEMBL3715 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8057281	Inhibitor 8297	1670.0 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Partial seizures 8 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020646s021lbl.pdf	Primary	Approved 8429	GABITRIL Approved Use GABITRIL (tiagabine hydrochloride) is indicated as adjunctive therapy in adults and children 12 years and older in the treatment of partial seizures. Launch Date 1997
Anxiety 267 Sources: https://clinicaltrials.gov/ct2/show/NCT00236015	Primary	Phase III 656	GABITRIL Approved Use GABITRIL (tiagabine hydrochloride) is indicated as adjunctive therapy in adults and children 12 years and older in the treatment of partial seizures. Launch Date 1997
Cocaine-related disorders 19 Sources: https://clinicaltrials.gov/ct2/show/NCT00129298	Primary	Phase II 1132	GABITRIL Approved Use GABITRIL (tiagabine hydrochloride) is indicated as adjunctive therapy in adults and children 12 years and older in the treatment of partial seizures. Launch Date 1997

C_max

Value	Dose	Co-administered	Analyte	Population
552 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7555975	24 mg single, oral dose: 24 mg route of administration: Oral experiment type: SINGLE co-administered:		TIAGABINE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
265 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7555975	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:		TIAGABINE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
2190 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7555975	24 mg single, oral dose: 24 mg route of administration: Oral experiment type: SINGLE co-administered:		TIAGABINE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
826 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7555975	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:		TIAGABINE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.3 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7555975	24 mg single, oral dose: 24 mg route of administration: Oral experiment type: SINGLE co-administered:		TIAGABINE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.5 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7555975	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:		TIAGABINE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
320 mg single, oral Overdose Dose: 320 mg Route: oral Route: single Dose: 320 mg Co-administed with:: phenytoin, p.o(400 mg, single) Sources: https://pubmed.ncbi.nlm.nih.gov/7670769 Page: p.155	unhealthy, 30 n = 1 Health Status: unhealthy Condition: Seizures Age Group: 30 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/7670769 Page: p.155	Disc. AE: Drowsiness, Coma... AEs leading to discontinuation/dose reduction: Drowsiness Coma (grade 3) Sources: https://pubmed.ncbi.nlm.nih.gov/7670769 Page: p.155
72 mg single, oral Overdose Dose: 72 mg Route: oral Route: single Dose: 72 mg Sources: https://pubmed.ncbi.nlm.nih.gov/15388215 Page: p.271	unhealthy, 46 n = 1 Health Status: unhealthy Condition: Depression Age Group: 46 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/15388215 Page: p.271	Disc. AE: Stupor, Confusion... AEs leading to discontinuation/dose reduction: Stupor Confusion Sources: https://pubmed.ncbi.nlm.nih.gov/15388215 Page: p.271

AEs

AE	Significance	Dose	Population
Drowsiness	Disc. AE	320 mg single, oral Overdose Dose: 320 mg Route: oral Route: single Dose: 320 mg Co-administed with:: phenytoin, p.o(400 mg, single) Sources: https://pubmed.ncbi.nlm.nih.gov/7670769 Page: p.155	unhealthy, 30 n = 1 Health Status: unhealthy Condition: Seizures Age Group: 30 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/7670769 Page: p.155
Coma	grade 3 Disc. AE	320 mg single, oral Overdose Dose: 320 mg Route: oral Route: single Dose: 320 mg Co-administed with:: phenytoin, p.o(400 mg, single) Sources: https://pubmed.ncbi.nlm.nih.gov/7670769 Page: p.155	unhealthy, 30 n = 1 Health Status: unhealthy Condition: Seizures Age Group: 30 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/7670769 Page: p.155
Confusion	Disc. AE	72 mg single, oral Overdose Dose: 72 mg Route: oral Route: single Dose: 72 mg Sources: https://pubmed.ncbi.nlm.nih.gov/15388215 Page: p.271	unhealthy, 46 n = 1 Health Status: unhealthy Condition: Depression Age Group: 46 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/15388215 Page: p.271
Stupor	Disc. AE	72 mg single, oral Overdose Dose: 72 mg Route: oral Route: single Dose: 72 mg Sources: https://pubmed.ncbi.nlm.nih.gov/15388215 Page: p.271	unhealthy, 46 n = 1 Health Status: unhealthy Condition: Depression Age Group: 46 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/15388215 Page: p.271

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9586	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9586
MolPort	MolPort-006-167-658	https://www.molport.com/shop/molecule-link/MolPort-006-167-658
ZINC	ZINC000003831531	http://zinc15.docking.org/substances/ZINC000003831531
eMolecules	902575	https://www.emolecules.com/cgi-bin/more?vid=902575

PubMed

Title	Date	PubMed
Concerns with antiepileptic drug initiation: safety, tolerability, and efficacy.	2001	11564122
Tiagabine improves panic and agoraphobia in panic disorder patients.	2001 Aug	11561942
Metabolic distinction between vesicular and cytosolic GABA in cultured GABAergic neurons using 13C magnetic resonance spectroscopy.	2001 Feb 15	11170185
[Antiepileptic drugs and neuropathic pain].	2001 Feb 16-28	11333392
Transient dystonias in three patients treated with tiagabine.	2001 Jul	11488897
Improvement of stiff-person syndrome with tiagabine.	2001 Jul 24	11468338
Tiagabine, a specific gamma-aminobutyric acid transporter-1 inhibitor, in the treatment of psychosis.	2001 Jun	11386503
[An open study of tiagabine in partial epilepsy].	2001 Jun 1-15	11562825
Assessing tinnitus and prospective tinnitus therapeutics using a psychophysical animal model.	2001 Mar	11545150
Status epilepticus and tiagabine therapy: review of safety data and epidemiologic comparisons.	2001 Mar	11442155
The GABA uptake inhibitor tiagabine promotes slow wave sleep in normal elderly subjects.	2001 Mar-Apr	11182474
Treatment of epilepsy in women of reproductive age: pharmacokinetic considerations.	2002	12102641
Interactions between antiepileptic drugs and hormonal contraception.	2002	11945109
Increased [(3)H]tiagabine binding to GAT-1 in the cingulate cortex in schizophrenia.	2002	11803235
Occurrence of psychosis in patients with epilepsy randomized to tiagabine or placebo treatment.	2002 Apr	11952769
The importance of drug interactions in epilepsy therapy.	2002 Apr	11952767
Effects of tiagabine and diazepam on operant ethanol self-administration in the rat.	2002 Jan	11925051
Tiagabine overdose can induce convulsive status epilepticus.	2002 Jul	12102683
Tiagabine, a gamma-amino-butyric acid transporter inhibitor impairs spatial learning of rats in the Morris water-maze.	2002 Jul 18	12110474
Effects of antiepileptic drugs on visual function, with special reference to Vigabatrin.	2002 Jun	12059879
Recurrent complex partial status epilepticus associated with tiagabine rechallenge.	2002 Mar	12094558
Contribution of GABAergic cortical circuitry in shaping somatosensory evoked scalp responses: specific changes after single-dose administration of tiagabine.	2002 May	11976045

Patents

Sample Use Guides

In Vivo Use Guide

12-22 mg/day PO divided q8-12hr

Route of Administration: Oral

In Vitro Use Guide

The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) proliferation assay is based on conversion by mitochondrial dehydrogenases of the substrate containing a tetrazolium ring into blue formazan, detectable spectrophotometrically (10). The level of blue formazan is then used as indirect index of cell density. The astrocytes were set up in flat-bottomed 200-μl microplates, incubated at 37◦C in a humidified 5% CO2/95% air mixture, and treated with 1, 10, 50, and 100 μg/ml of Tiagabine for 48 h. Four hours before the end of the culture, 20 μl of 0.5% 3-(4,5-dimethylthiazol-2-yl)diphenyltetrazolium bromide in phosphate-buffered saline (PBS) was added to each microwell. After the incubation with the reagent, the supernatant was removed and replaced with 100 μl of acidified isopropanol and 20 μl of 3% (wt/vol) sodium dodecylsulfate (SDS) in water. The optical density of each sample was measured with a microplate spectrophotometer reader (Titertek Multiskan, Flow Laboratories) at 570 nm, and four replicates were performed for each sample.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 16:52:35 GMT 2023` Edited by `admin` on `Sat Dec 16 16:52:35 GMT 2023`
Record UNII	Z80I64HMNP
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

TIAGABINE

Official Name

English

NO-050328 FREE BASE

Code

English

ABBOTT-705691 FREE BASE

Code

English

(-)-(R)-1-(4,4-BIS(3-METHYL-2-THIENYL)-3-BUTENYL)NIPECOTIC ACID

Systematic Name

English

ABT-569 FREE BASE

Code

English

tiagabine [INN]

Common Name

English

3-PIPERIDINECARBOXYLIC ACID, 1-(4,4-BIS(3-METHYL-2-THIENYL)-3-BUTEN-1-YL)-, (3R)-

Systematic Name

English

ABBOTT-70569 FREE BASE

Code

English

TIAGABINE [HSDB]

Common Name

English

TIAGABINE [VANDF]

Common Name

English

TIAGABINE [MI]

Common Name

English

NNC-050328 FREE BASE

Code

English

3-PIPERIDINECARBOXYLIC ACID, 1-(4,4-BIS(3-METHYL-2-THIENYL)-3-BUTENYL)-, (R)-

Systematic Name

English

Tiagabine [WHO-DD]

Common Name

English

(3R)-1-(4,4-BIS(3-METHYL-2-THIENYL)-3-BUTEN-1-YL)-3-PIPERIDINECARBOXYLIC ACID

Systematic Name

English

Classification Tree Code System Code

LIVERTOX

NBK548376