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
Clinical evaluation of Gabitril and Lamictal for drug-resistant epilepsy in adults.	2001	11977339
[Hormonal contraception and epilepsy].	2001	11799750
Second generation anticonvulsant medications: their use in children.	2001 Apr	11885112
[Monitoring of renal function in epileptic children and teenagers treated with valproic acid or carbamazepine in concomitant therapy with tiagabine].	2001 Dec	11899842
Clinical pharmacology and therapeutic use of the new antiepileptic drugs.	2001 Dec	11860529
Pharmacological characterization of the 6 Hz psychomotor seizure model of partial epilepsy.	2001 Dec	11738929
Visual fields and tiagabine: a quandary.	2001 Oct	11749112
New and emerging prophylactic agents for migraine.	2002	12153333
Tiagabine add-on for drug-resistant partial epilepsy.	2002	12137637
Treatment of epilepsy in women of reproductive age: pharmacokinetic considerations.	2002	12102641
Mood disorders in patients with epilepsy: epidemiology and management.	2002	11994019
Cellular mechanisms of pharmacoresistance in slices from epilepsy surgery.	2002	11990776
Interactions between antiepileptic drugs and hormonal contraception.	2002	11945109
Effect of antiepileptic drugs on cognitive function in individuals with epilepsy: a comparative review of newer versus older agents.	2002	11893228
Anticonvulsants: aspects of their mechanisms of action.	2002	11888234
Seizures in HIV-seropositive individuals: epidemiology and treatment.	2002	11825100
Increased [(3)H]tiagabine binding to GAT-1 in the cingulate cortex in schizophrenia.	2002	11803235
The 'number needed to treat' with levetiracetam (LEV): comparison with the other new antiepileptic drugs (AEDs).	2002 Apr	12185762
Third generation anticonvulsants in bipolar disorder: a review of efficacy and summary of clinical recommendations.	2002 Apr	12000201
Free-choice ethanol consumption under the influence of GABAergic drugs in rats.	2002 Apr	11981120
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
Correlation between anticonvulsant activity and inhibitory action on glial gamma-aminobutyric acid uptake of the highly selective mouse gamma-aminobutyric acid transporter 1 inhibitor 3-hydroxy-4-amino-4,5,6,7-tetrahydro-1,2-benzisoxazole and its N-alkylated analogs.	2002 Aug	12130726
Neuroprotective effect of tiagabine in transient forebrain global ischemia: an in vivo microdialysis, behavioral, and histological study.	2002 Aug 16	12137918
Selective suppression of hippocampal region hyperexcitability related to seizure susceptibility in epileptic El mice by the GABA-transporter inhibitor tiagabine.	2002 Aug 30	12176163
New antiepileptic drugs: review on drug interactions.	2002 Feb	11805729
Marketed new antiepileptic drugs: are they better than old-generation agents?	2002 Feb	11805726
Effects of tiagabine and diazepam on operant ethanol self-administration in the rat.	2002 Jan	11925051
Non-convulsive status epilepticus induced by tiagabine in a patient with pseudoseizure.	2002 Jan	11888262
The use of tiagabine in affective disorders.	2002 Jan	11819159
Appropriate use of medications for seizures. Guiding principles on the path of efficacy.	2002 Jan	11810752
Bi-directional transport of GABA in human embryonic kidney (HEK-293) cells stably expressing the rat GABA transporter GAT-1.	2002 Jan	11786484
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
Aggravation of partial seizures by antiepileptic drugs: is there evidence from clinical trials?	2002 Jul 9	12105311
Effects of antiepileptic drugs on visual function, with special reference to Vigabatrin.	2002 Jun	12059879
Tiagabine-related non-convulsive status epilepticus in partial epilepsy: three case reports and a review of the literature.	2002 Jun	12027571
Some common issues in the use of antiepileptic drugs.	2002 Mar	12170391
Recurrent complex partial status epilepticus associated with tiagabine rechallenge.	2002 Mar	12094558
Tiagabine in glial tumors.	2002 Mar	11948010
Visual field defects.	2002 Mar	11945104
[Adult GM2 gangliosidosis: improvement of ataxia with GABAergic drugs].	2002 Mar	11927106
Anxiolytic-like effects of acute and chronic GABA transporter inhibition in rats.	2002 May	12111474
[New antiepileptic drugs: new therapeutic options].	2002 May	11997751
Contribution of GABAergic cortical circuitry in shaping somatosensory evoked scalp responses: specific changes after single-dose administration of tiagabine.	2002 May	11976045
Effects of tiagabine, a gamma-aminobutyric acid re-uptake inhibitor, on normal rat bladder function.	2002 May	11956486
Comparison of antiepileptic drugs tiagabine, lamotrigine, and gabapentin in mouse models of acute, prolonged, and chronic nociception.	2002 Sep	12183677
An open case series on the utility of tiagabine as an augmentation in refractory bipolar outpatients.	2002 Sep	12167526
[(3)H]Tiagabine binding to GABA transporter-1 (GAT-1) in suicidal depression.	2002 Sep	12167498
New antiepileptic drugs in childhood.	2002 Sep	12094136

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