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:: 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

8.7557761E11
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

8.7557761E11
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
Co-administed with::
phenytoin, p.o(400 mg, single)
Sources: Page: p.155
unhealthy, 30
n = 1
Health Status: unhealthy
Condition: Seizures
Age Group: 30
Sex: M
Population Size: 1
Sources: Page: p.155
Disc. AE: Drowsiness, Coma...
AEs leading to
discontinuation/dose reduction:
Drowsiness
Coma (grade 3)
Sources: Page: p.155
72 mg single, oral
Overdose
Dose: 72 mg
Route: oral
Route: single
Dose: 72 mg
Sources: Page: p.271
unhealthy, 46
n = 1
Health Status: unhealthy
Condition: Depression
Age Group: 46
Sex: F
Population Size: 1
Sources: Page: p.271
Disc. AE: Stupor, Confusion...
AEs leading to
discontinuation/dose reduction:
Stupor
Confusion
Sources: Page: p.271
AEs

AEs

AESignificanceDosePopulation
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: Page: p.155
unhealthy, 30
n = 1
Health Status: unhealthy
Condition: Seizures
Age Group: 30
Sex: M
Population Size: 1
Sources: 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: Page: p.155
unhealthy, 30
n = 1
Health Status: unhealthy
Condition: Seizures
Age Group: 30
Sex: M
Population Size: 1
Sources: Page: p.155
Confusion Disc. AE
72 mg single, oral
Overdose
Dose: 72 mg
Route: oral
Route: single
Dose: 72 mg
Sources: Page: p.271
unhealthy, 46
n = 1
Health Status: unhealthy
Condition: Depression
Age Group: 46
Sex: F
Population Size: 1
Sources: Page: p.271
Stupor Disc. AE
72 mg single, oral
Overdose
Dose: 72 mg
Route: oral
Route: single
Dose: 72 mg
Sources: Page: p.271
unhealthy, 46
n = 1
Health Status: unhealthy
Condition: Depression
Age Group: 46
Sex: F
Population Size: 1
Sources: Page: p.271
PubMed

PubMed

TitleDatePubMed
Psychiatric symptoms after therapy with new antiepileptic drugs: psychopathological and seizure related variables.
2000 Jun
Clinical evaluation of Gabitril and Lamictal for drug-resistant epilepsy in adults.
2001
Concerns with antiepileptic drug initiation: safety, tolerability, and efficacy.
2001
Tiagabine in clinical practice.
2001
The management of refractory idiopathic epilepsies.
2001
Epileptic encephalopathy.
2001
GABAergic mechanisms in epilepsy.
2001
The new generation of GABA enhancers. Potential in the treatment of epilepsy.
2001
Behavioural effects of the new anticonvulsants.
2001
Effects of antiepileptic drugs on cognition.
2001
Newer antiepileptic drugs: advantages and disadvantages.
2001 Aug
Pharmacological characterization of the 6 Hz psychomotor seizure model of partial epilepsy.
2001 Dec
Progress report on new antiepileptic drugs: a summary of the Fifth Eilat Conference (EILAT V).
2001 Jan
Advances in the treatment of epilepsy.
2001 Jul 1
Improvement of stiff-person syndrome with tiagabine.
2001 Jul 24
Pharmacologic management of epilepsy in the elderly.
2001 May-Jun
Antiepileptic drugs for the acute and maintenance treatment of bipolar disorder.
2001 Sep-Oct
The 'number needed to treat' with levetiracetam (LEV): comparison with the other new antiepileptic drugs (AEDs).
2002 Apr
Tiagabine overdose can induce convulsive status epilepticus.
2002 Jul
Aggravation of partial seizures by antiepileptic drugs: is there evidence from clinical trials?
2002 Jul 9
Tiagabine in glial tumors.
2002 Mar
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
Comparison of antiepileptic drugs tiagabine, lamotrigine, and gabapentin in mouse models of acute, prolonged, and chronic nociception.
2002 Sep
An open case series on the utility of tiagabine as an augmentation in refractory bipolar outpatients.
2002 Sep
[(3)H]Tiagabine binding to GABA transporter-1 (GAT-1) in suicidal depression.
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