TIAGABINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H25NO2S2
Molecular Weight	375.5509
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cc1ccsc1C(=CCCN2CCC[C@]([H])(C2)C(=O)O)c3c(C)ccs3

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

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020646s021lbl.pdf
Curator's Comment:: 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	Condition	Potency
GABA transporter 1 7 Target ID: CHEMBL1903 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8057281	Inhibitor 7701	Partial seizures Anxiety Cocaine-related disorders	70 nM [IC50]
GABA transporter 3 5 Target ID: CHEMBL5208 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8057281	Inhibitor 7701		917 µM [IC50]
Betaine transporter 4 Target ID: CHEMBL3715 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8057281	Inhibitor 7701		1670 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Partial seizures 7 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020646s021lbl.pdf	Primary	GABA transporter 1	Approved 7997	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 875577600000
Anxiety 245 Sources: https://clinicaltrials.gov/ct2/show/NCT00236015	Primary	GABA transporter 1	Phase III 650	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 875577600000
Cocaine-related disorders 14 Sources: https://clinicaltrials.gov/ct2/show/NCT00129298	Primary	GABA transporter 1	Phase II	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 875577600000

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 Sources: https://pubmed.ncbi.nlm.nih.gov/7670769	unhealthy, 30 Health Status: unhealthy Age Group: 30 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/7670769	Disc. AE: Drowsiness, Coma... AEs leading to discontinuation/dose reduction: Drowsiness Coma (grade 3) Sources: https://pubmed.ncbi.nlm.nih.gov/7670769
72 mg single, oral Overdose Dose: 72 mg Route: oral Route: single Dose: 72 mg Sources: https://pubmed.ncbi.nlm.nih.gov/15388215	unhealthy, 46 Health Status: unhealthy Age Group: 46 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/15388215	Disc. AE: Stupor, Confusion... AEs leading to discontinuation/dose reduction: Stupor Confusion Sources: https://pubmed.ncbi.nlm.nih.gov/15388215

AEs

AE	Significance	Dose	Population
Drowsiness	Disc. AE	320 mg single, oral Overdose Dose: 320 mg Route: oral Route: single Dose: 320 mg Sources: https://pubmed.ncbi.nlm.nih.gov/7670769	unhealthy, 30 Health Status: unhealthy Age Group: 30 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/7670769
Coma	grade 3 Disc. AE	320 mg single, oral Overdose Dose: 320 mg Route: oral Route: single Dose: 320 mg Sources: https://pubmed.ncbi.nlm.nih.gov/7670769	unhealthy, 30 Health Status: unhealthy Age Group: 30 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/7670769
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	unhealthy, 46 Health Status: unhealthy Age Group: 46 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/15388215
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	unhealthy, 46 Health Status: unhealthy Age Group: 46 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/15388215

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

PubMed

Title	Date	PubMed
Clinical evaluation of Gabitril and Lamictal for drug-resistant epilepsy in adults.	2001	11977339
[New antiepileptic drugs in childhood epilepsies: indications and limits].	2001	11827845
[Hormonal contraception and epilepsy].	2001	11799750
Developments in mood stabilisers.	2001	11719917
Epilepsy in the elderly: the use of tiagabine.	2001	11520325
Tiagabine (gabitril) experience in children.	2001	11520324
Long-term safety of tiagabine.	2001	11520323
Tiagabine in clinical practice.	2001	11520322
The management of refractory idiopathic epilepsies.	2001	11520320
Second generation anticonvulsant medications: their use in children.	2001 Apr	11885112
Tiagabine improves panic and agoraphobia in panic disorder patients.	2001 Aug	11561942
[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
Treatment of painful sensory neuropathy with tiagabine: a pilot study.	2001 Dec	11794716
Pharmacological characterization of the 6 Hz psychomotor seizure model of partial epilepsy.	2001 Dec	11738929
Assessing tinnitus and prospective tinnitus therapeutics using a psychophysical animal model.	2001 Mar	11545150
Visual fields and tiagabine: a quandary.	2001 Oct	11749112
Antiepileptic drugs for the acute and maintenance treatment of bipolar disorder.	2001 Sep-Oct	11553525
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
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
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
New antiepileptic drugs: review on drug interactions.	2002 Feb	11805729
Marketed new antiepileptic drugs: are they better than old-generation agents?	2002 Feb	11805726
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
Recurrent complex partial status epilepticus associated with tiagabine rechallenge.	2002 Mar	12094558
Tiagabine in glial tumors.	2002 Mar	11948010
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
An open case series on the utility of tiagabine as an augmentation in refractory bipolar outpatients.	2002 Sep	12167526
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.

Name

Type

Language

TIAGABINE

Official Name

English

NO-050328 FREE BASE

Code

English

TIAGABINE [WHO-DD]

Common Name

English

ABBOTT-705691 FREE BASE

Code

English

ABT-569 FREE BASE

Code

English

TIAGABINE [INN]

Common 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

Classification Tree Code System Code

LIVERTOX

959