U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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 of TIAGABINE

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
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.

Originator

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

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
70 nM [IC50]
917 µM [IC50]
1670 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

875577600000
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

875577600000
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:
PubMed

PubMed

TitleDatePubMed
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
Developments in mood stabilisers.
2001
Epilepsy in the elderly: the use of tiagabine.
2001
Tiagabine (gabitril) experience in children.
2001
Long-term safety of tiagabine.
2001
Tiagabine in clinical practice.
2001
The management of refractory idiopathic epilepsies.
2001
Second generation anticonvulsant medications: their use in children.
2001 Apr
Tiagabine improves panic and agoraphobia in panic disorder patients.
2001 Aug
[Monitoring of renal function in epileptic children and teenagers treated with valproic acid or carbamazepine in concomitant therapy with tiagabine].
2001 Dec
Clinical pharmacology and therapeutic use of the new antiepileptic drugs.
2001 Dec
Treatment of painful sensory neuropathy with tiagabine: a pilot study.
2001 Dec
Pharmacological characterization of the 6 Hz psychomotor seizure model of partial epilepsy.
2001 Dec
Assessing tinnitus and prospective tinnitus therapeutics using a psychophysical animal model.
2001 Mar
Visual fields and tiagabine: a quandary.
2001 Oct
Antiepileptic drugs for the acute and maintenance treatment of bipolar disorder.
2001 Sep-Oct
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
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
The 'number needed to treat' with levetiracetam (LEV): comparison with the other new antiepileptic drugs (AEDs).
2002 Apr
Third generation anticonvulsants in bipolar disorder: a review of efficacy and summary of clinical recommendations.
2002 Apr
Free-choice ethanol consumption under the influence of GABAergic drugs in rats.
2002 Apr
Occurrence of psychosis in patients with epilepsy randomized to tiagabine or placebo treatment.
2002 Apr
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
Neuroprotective effect of tiagabine in transient forebrain global ischemia: an in vivo microdialysis, behavioral, and histological study.
2002 Aug 16
New antiepileptic drugs: review on drug interactions.
2002 Feb
Marketed new antiepileptic drugs: are they better than old-generation agents?
2002 Feb
Non-convulsive status epilepticus induced by tiagabine in a patient with pseudoseizure.
2002 Jan
The use of tiagabine in affective disorders.
2002 Jan
Appropriate use of medications for seizures. Guiding principles on the path of efficacy.
2002 Jan
Bi-directional transport of GABA in human embryonic kidney (HEK-293) cells stably expressing the rat GABA transporter GAT-1.
2002 Jan
Tiagabine overdose can induce convulsive status epilepticus.
2002 Jul
Tiagabine, a gamma-amino-butyric acid transporter inhibitor impairs spatial learning of rats in the Morris water-maze.
2002 Jul 18
Aggravation of partial seizures by antiepileptic drugs: is there evidence from clinical trials?
2002 Jul 9
Effects of antiepileptic drugs on visual function, with special reference to Vigabatrin.
2002 Jun
Tiagabine-related non-convulsive status epilepticus in partial epilepsy: three case reports and a review of the literature.
2002 Jun
Recurrent complex partial status epilepticus associated with tiagabine rechallenge.
2002 Mar
Tiagabine in glial tumors.
2002 Mar
Anxiolytic-like effects of acute and chronic GABA transporter inhibition in rats.
2002 May
[New antiepileptic drugs: new therapeutic options].
2002 May
Contribution of GABAergic cortical circuitry in shaping somatosensory evoked scalp responses: specific changes after single-dose administration of tiagabine.
2002 May
Effects of tiagabine, a gamma-aminobutyric acid re-uptake inhibitor, on normal rat bladder function.
2002 May
An open case series on the utility of tiagabine as an augmentation in refractory bipolar outpatients.
2002 Sep
New antiepileptic drugs in childhood.
2002 Sep
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.
Name Type Language
TIAGABINE
HSDB   INN   MI   VANDF   WHO-DD  
INN  
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
Created by admin on Sat Jun 26 06:06:51 UTC 2021 , Edited by admin on Sat Jun 26 06:06:51 UTC 2021
NDF-RT N0000175753
Created by admin on Sat Jun 26 06:06:51 UTC 2021 , Edited by admin on Sat Jun 26 06:06:51 UTC 2021
NDF-RT N0000008486
Created by admin on Sat Jun 26 06:06:51 UTC 2021 , Edited by admin on Sat Jun 26 06:06:51 UTC 2021
WHO-VATC QN03AG06
Created by admin on Sat Jun 26 06:06:51 UTC 2021 , Edited by admin on Sat Jun 26 06:06:51 UTC 2021
NCI_THESAURUS C264
Created by admin on Sat Jun 26 06:06:51 UTC 2021 , Edited by admin on Sat Jun 26 06:06:51 UTC 2021
WHO-ATC N03AG06
Created by admin on Sat Jun 26 06:06:51 UTC 2021 , Edited by admin on Sat Jun 26 06:06:51 UTC 2021
Code System Code Type Description
MESH
C059205
Created by admin on Sat Jun 26 06:06:51 UTC 2021 , Edited by admin on Sat Jun 26 06:06:51 UTC 2021
PRIMARY
MERCK INDEX
M10842
Created by admin on Sat Jun 26 06:06:51 UTC 2021 , Edited by admin on Sat Jun 26 06:06:51 UTC 2021
PRIMARY Merck Index
RXCUI
31914
Created by admin on Sat Jun 26 06:06:51 UTC 2021 , Edited by admin on Sat Jun 26 06:06:51 UTC 2021
PRIMARY RxNorm
INN
6306
Created by admin on Sat Jun 26 06:06:51 UTC 2021 , Edited by admin on Sat Jun 26 06:06:51 UTC 2021
PRIMARY
WIKIPEDIA
TIAGABINE
Created by admin on Sat Jun 26 06:06:51 UTC 2021 , Edited by admin on Sat Jun 26 06:06:51 UTC 2021
PRIMARY
ChEMBL
CHEMBL1027
Created by admin on Sat Jun 26 06:06:51 UTC 2021 , Edited by admin on Sat Jun 26 06:06:51 UTC 2021
PRIMARY
CAS
115103-54-3
Created by admin on Sat Jun 26 06:06:51 UTC 2021 , Edited by admin on Sat Jun 26 06:06:51 UTC 2021
PRIMARY
DRUG BANK
DB00906
Created by admin on Sat Jun 26 06:06:51 UTC 2021 , Edited by admin on Sat Jun 26 06:06:51 UTC 2021
PRIMARY
FDA UNII
Z80I64HMNP
Created by admin on Sat Jun 26 06:06:51 UTC 2021 , Edited by admin on Sat Jun 26 06:06:51 UTC 2021
PRIMARY
NCI_THESAURUS
C66602
Created by admin on Sat Jun 26 06:06:51 UTC 2021 , Edited by admin on Sat Jun 26 06:06:51 UTC 2021
PRIMARY
IUPHAR
4818
Created by admin on Sat Jun 26 06:06:51 UTC 2021 , Edited by admin on Sat Jun 26 06:06:51 UTC 2021
PRIMARY
PUBCHEM
60648
Created by admin on Sat Jun 26 06:06:51 UTC 2021 , Edited by admin on Sat Jun 26 06:06:51 UTC 2021
PRIMARY
EVMPD
SUB11000MIG
Created by admin on Sat Jun 26 06:06:51 UTC 2021 , Edited by admin on Sat Jun 26 06:06:51 UTC 2021
PRIMARY
DRUG CENTRAL
2648
Created by admin on Sat Jun 26 06:06:51 UTC 2021 , Edited by admin on Sat Jun 26 06:06:51 UTC 2021
PRIMARY
EPA CompTox
115103-54-3
Created by admin on Sat Jun 26 06:06:51 UTC 2021 , Edited by admin on Sat Jun 26 06:06:51 UTC 2021
PRIMARY
LACTMED
Tiagabine
Created by admin on Sat Jun 26 06:06:51 UTC 2021 , Edited by admin on Sat Jun 26 06:06:51 UTC 2021
PRIMARY
HSDB
7527
Created by admin on Sat Jun 26 06:06:51 UTC 2021 , Edited by admin on Sat Jun 26 06:06:51 UTC 2021
PRIMARY