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
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
| 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 |
DescriptionCurator'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
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
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL1903 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8057281 |
70.0 nM [IC50] | ||
Target ID: CHEMBL5208 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8057281 |
917.0 µM [IC50] | ||
Target ID: CHEMBL3715 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8057281 |
1670.0 µM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | GABITRIL Approved UseGABITRIL (tiagabine hydrochloride) is indicated as adjunctive therapy in adults and children 12 years and older in the treatment of partial seizures. Launch Date1997 |
|||
| Primary | GABITRIL Approved UseGABITRIL (tiagabine hydrochloride) is indicated as adjunctive therapy in adults and children 12 years and older in the treatment of partial seizures. Launch Date1997 |
|||
| Primary | GABITRIL Approved UseGABITRIL (tiagabine hydrochloride) is indicated as adjunctive therapy in adults and children 12 years and older in the treatment of partial seizures. Launch Date1997 |
Cmax
| 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 |
T1/2
| 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 |
unhealthy, 30 |
Disc. AE: Drowsiness, Coma... AEs leading to discontinuation/dose reduction: Drowsiness Sources: Coma (grade 3) |
72 mg single, oral Overdose |
unhealthy, 46 |
Disc. AE: Stupor, Confusion... AEs leading to discontinuation/dose reduction: Stupor Sources: Confusion |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Drowsiness | Disc. AE | 320 mg single, oral Overdose |
unhealthy, 30 |
| Coma | grade 3 Disc. AE |
320 mg single, oral Overdose |
unhealthy, 30 |
| Confusion | Disc. AE | 72 mg single, oral Overdose |
unhealthy, 46 |
| Stupor | Disc. AE | 72 mg single, oral Overdose |
unhealthy, 46 |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| unlikely | ||||
| unlikely | ||||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020646ap_gabitril_phrmr.pdf#page=14 Page: 14.0 |
yes |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020646ap_gabitril_phrmr.pdf#page=13 Page: 13.0 |
likely | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020646ap_gabitril_phrmr.pdf#page=14 Page: 14.0 |
likely | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020646ap_gabitril_phrmr.pdf#page=13 Page: 13.0 |
likely | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020646ap_gabitril_phrmr.pdf#page=13 Page: 13.0 |
no | |||
| no | ||||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020646ap_gabitril_phrmr.pdf#page=13 Page: 13.0 |
yes |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| 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 |
Sample Use Guides
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/14511393
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
Edited
Tue Apr 01 22:30:02 GMT 2025
by
admin
on
Tue Apr 01 22:30:02 GMT 2025
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| Record UNII |
OXB00SKC7R
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| Record Status |
Validated (UNII)
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| Record Version |
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