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Details

Stereochemistry ABSOLUTE
Molecular Formula C20H25NO2S2.ClH.H2O
Molecular Weight 430.024
Optical Activity ( - )
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TIAGABINE HYDROCHLORIDE MONOHYDRATE

SMILES

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

InChI

InChIKey=KOZCGZMZXXVHCF-GGMCWBHBSA-N
InChI=1S/C20H25NO2S2.ClH.H2O/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);1H;1H2/t16-;;/m1../s1

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
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.

Originator

Sources: International Congress Series (1987), 750, (Pharmacology), 125-8.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
70.0 nM [IC50]
917.0 µM [IC50]
1670.0 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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
Primary
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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
552 ng/mL
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
2190 ng × h/mL
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
7.3 h
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
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

Doses

DosePopulationAdverse events​
320 mg single, oral
Overdose
Dose: 320 mg
Route: oral
Route: single
Dose: 320 mg
Sources:
unhealthy, 30
Health Status: unhealthy
Age Group: 30
Sex: M
Sources:
Disc. AE: Drowsiness, Coma...
AEs leading to
discontinuation/dose reduction:
Drowsiness
Coma (grade 3)
Sources:
72 mg single, oral
Overdose
Dose: 72 mg
Route: oral
Route: single
Dose: 72 mg
Sources:
unhealthy, 46
Health Status: unhealthy
Age Group: 46
Sex: F
Sources:
Disc. AE: Stupor, Confusion...
AEs leading to
discontinuation/dose reduction:
Stupor
Confusion
Sources:
AEs

AEs

AESignificanceDosePopulation
Drowsiness Disc. AE
320 mg single, oral
Overdose
Dose: 320 mg
Route: oral
Route: single
Dose: 320 mg
Sources:
unhealthy, 30
Health Status: unhealthy
Age Group: 30
Sex: M
Sources:
Coma grade 3
Disc. AE
320 mg single, oral
Overdose
Dose: 320 mg
Route: oral
Route: single
Dose: 320 mg
Sources:
unhealthy, 30
Health Status: unhealthy
Age Group: 30
Sex: M
Sources:
Confusion Disc. AE
72 mg single, oral
Overdose
Dose: 72 mg
Route: oral
Route: single
Dose: 72 mg
Sources:
unhealthy, 46
Health Status: unhealthy
Age Group: 46
Sex: F
Sources:
Stupor Disc. AE
72 mg single, oral
Overdose
Dose: 72 mg
Route: oral
Route: single
Dose: 72 mg
Sources:
unhealthy, 46
Health Status: unhealthy
Age Group: 46
Sex: F
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer







Drug as perpetrator​Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Comparison of antiepileptic drugs tiagabine, lamotrigine, and gabapentin in mouse models of acute, prolonged, and chronic nociception.
2002-09
An open case series on the utility of tiagabine as an augmentation in refractory bipolar outpatients.
2002-09
[(3)H]Tiagabine binding to GABA transporter-1 (GAT-1) in suicidal depression.
2002-09
New antiepileptic drugs in childhood.
2002-09
Selective suppression of hippocampal region hyperexcitability related to seizure susceptibility in epileptic El mice by the GABA-transporter inhibitor tiagabine.
2002-08-30
Neuroprotective effect of tiagabine in transient forebrain global ischemia: an in vivo microdialysis, behavioral, and histological study.
2002-08-16
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.
2002-08
Tiagabine, a gamma-amino-butyric acid transporter inhibitor impairs spatial learning of rats in the Morris water-maze.
2002-07-18
Aggravation of partial seizures by antiepileptic drugs: is there evidence from clinical trials?
2002-07-09
Tiagabine overdose can induce convulsive status epilepticus.
2002-07
Effects of antiepileptic drugs on visual function, with special reference to Vigabatrin.
2002-06
Tiagabine-related non-convulsive status epilepticus in partial epilepsy: three case reports and a review of the literature.
2002-06
Anxiolytic-like effects of acute and chronic GABA transporter inhibition in rats.
2002-05
[New antiepileptic drugs: new therapeutic options].
2002-05
Contribution of GABAergic cortical circuitry in shaping somatosensory evoked scalp responses: specific changes after single-dose administration of tiagabine.
2002-05
Effects of tiagabine, a gamma-aminobutyric acid re-uptake inhibitor, on normal rat bladder function.
2002-05
The 'number needed to treat' with levetiracetam (LEV): comparison with the other new antiepileptic drugs (AEDs).
2002-04
Third generation anticonvulsants in bipolar disorder: a review of efficacy and summary of clinical recommendations.
2002-04
Free-choice ethanol consumption under the influence of GABAergic drugs in rats.
2002-04
Occurrence of psychosis in patients with epilepsy randomized to tiagabine or placebo treatment.
2002-04
The importance of drug interactions in epilepsy therapy.
2002-04
Some common issues in the use of antiepileptic drugs.
2002-03
Recurrent complex partial status epilepticus associated with tiagabine rechallenge.
2002-03
Tiagabine in glial tumors.
2002-03
Visual field defects.
2002-03
[Adult GM2 gangliosidosis: improvement of ataxia with GABAergic drugs].
2002-03
New antiepileptic drugs: review on drug interactions.
2002-02
Marketed new antiepileptic drugs: are they better than old-generation agents?
2002-02
Effects of tiagabine and diazepam on operant ethanol self-administration in the rat.
2002-01
Non-convulsive status epilepticus induced by tiagabine in a patient with pseudoseizure.
2002-01
The use of tiagabine in affective disorders.
2002-01
Appropriate use of medications for seizures. Guiding principles on the path of efficacy.
2002-01
Bi-directional transport of GABA in human embryonic kidney (HEK-293) cells stably expressing the rat GABA transporter GAT-1.
2002-01
New and emerging prophylactic agents for migraine.
2002
Tiagabine add-on for drug-resistant partial epilepsy.
2002
Treatment of epilepsy in women of reproductive age: pharmacokinetic considerations.
2002
Mood disorders in patients with epilepsy: epidemiology and management.
2002
Cellular mechanisms of pharmacoresistance in slices from epilepsy surgery.
2002
Interactions between antiepileptic drugs and hormonal contraception.
2002
Effect of antiepileptic drugs on cognitive function in individuals with epilepsy: a comparative review of newer versus older agents.
2002
Anticonvulsants: aspects of their mechanisms of action.
2002
Seizures in HIV-seropositive individuals: epidemiology and treatment.
2002
Increased [(3)H]tiagabine binding to GAT-1 in the cingulate cortex in schizophrenia.
2002
[Monitoring of renal function in epileptic children and teenagers treated with valproic acid or carbamazepine in concomitant therapy with tiagabine].
2001-12
Clinical pharmacology and therapeutic use of the new antiepileptic drugs.
2001-12
Treatment of painful sensory neuropathy with tiagabine: a pilot study.
2001-12
Second generation anticonvulsant medications: their use in children.
2001-04
Clinical evaluation of Gabitril and Lamictal for drug-resistant epilepsy in adults.
2001
[New antiepileptic drugs in childhood epilepsies: indications and limits].
2001
[Hormonal contraception and epilepsy].
2001
Patents

Sample Use Guides

12-22 mg/day PO divided q8-12hr
Route of Administration: Oral
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 Tue Apr 01 22:30:02 GMT 2025
Edited
by admin
on Tue Apr 01 22:30:02 GMT 2025
Record UNII
OXB00SKC7R
Record Status Validated (UNII)
Record Version
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Name Type Language
TIAGABINE HYDROCHLORIDE MONOHYDRATE
Common Name English
3-PIPERIDINECARBOXYLIC ACID, 1-(4,4-BIS(3-METHYL-2-THIENYL)-3-BUTEN-1-YL)-, HYDROCHLORIDE, HYDRATE (1:1:1), (3R)-
Preferred Name English
Code System Code Type Description
FDA UNII
OXB00SKC7R
Created by admin on Tue Apr 01 22:30:02 GMT 2025 , Edited by admin on Tue Apr 01 22:30:02 GMT 2025
PRIMARY
PUBCHEM
67065562
Created by admin on Tue Apr 01 22:30:02 GMT 2025 , Edited by admin on Tue Apr 01 22:30:02 GMT 2025
PRIMARY
CAS
145821-57-4
Created by admin on Tue Apr 01 22:30:02 GMT 2025 , Edited by admin on Tue Apr 01 22:30:02 GMT 2025
PRIMARY
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