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Identification
NameTiagabine
Accession NumberDB00906  (APRD00344)
TypeSmall Molecule
GroupsApproved
Description

Tiagabine is an anti-convulsive medication. It is also used in the treatment for panic disorder as are a few other anticonvulsants. Though the exact mechanism by which tiagabine exerts its effect on the human body is unknown, it does appear to operate as a selective GABA reuptake inhibitor.

Structure
Thumb
Synonyms
Gabitril
Tiagabina
Tiagabinum
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Gabitriltablet12 mg/1oralSTAT Rx USA LLC1997-11-03Not applicableUs
Gabitriltablet, film coated12 mg/1oralCephalon, Incorporated1997-11-03Not applicableUs
Gabitriltablet, film coated4 mg/1oralCephalon, Incorporated1997-11-03Not applicableUs
Gabitriltablet, film coated2 mg/1oralCephalon, Incorporated1997-11-03Not applicableUs
Gabitriltablet4 mg/1oralCarilion Materials Management1997-11-03Not applicableUs
Gabitriltablet4 mg/1oralLake Erie Medical & Surgial Supply DBA Quality Care Products LLC2011-11-15Not applicableUs
Gabitriltablet, film coated16 mg/1oralCephalon, Incorporated1997-11-03Not applicableUs
Tiagabine Hydrochloridetablet, film coated4 mg/1oralCima Labs Inc.2012-12-21Not applicableUs
Tiagabine Hydrochloridetablet, film coated2 mg/1oralCima Labs Inc.2012-12-21Not applicableUs
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Tiagabine Hydrochloridetablet, film coated2 mg/1oralSun Pharmaceutical Industries Limited2011-11-04Not applicableUs
Tiagabine Hydrochloridetablet, film coated4 mg/1oralSun Pharmaceutical Industries Limited2011-11-04Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Tiagabine hydrochloride
ThumbNot applicableDBSALT001255
Categories
UNIIZ80I64HMNP
CAS number115103-54-3
WeightAverage: 375.548
Monoisotopic: 375.132670429
Chemical FormulaC20H25NO2S2
InChI KeyInChIKey=PBJUNZJWGZTSKL-MRXNPFEDSA-N
InChI
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
IUPAC Name
(3R)-1-[4,4-bis(3-methylthiophen-2-yl)but-3-en-1-yl]piperidine-3-carboxylic acid
SMILES
CC1=C(SC=C1)C(=CCCN1CCC[[email protected]](C1)C(O)=O)C1=C(C)C=CS1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as piperidinecarboxylic acids. These are compounds containing a piperidine ring which bears a carboxylic acid group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPiperidines
Sub ClassPiperidinecarboxylic acids and derivatives
Direct ParentPiperidinecarboxylic acids
Alternative Parents
Substituents
  • Piperidinecarboxylic acid
  • Heteroaromatic compound
  • Thiophene
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of partial seizures
PharmacodynamicsTiagabine is used primarily as an anticonvulsant for the adjunctive treatment of epilepsy. 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.
Mechanism of actionThough the exact mechanism by which Tiagabine exerts its effect on the human body is unknown, it does appear to operate as a selective GABA reuptake inhibitor.
Related Articles
AbsorptionTiagabine is nearly completely absorbed (>95%).
Volume of distributionNot Available
Protein binding96%
Metabolism

Tiagabine is likely metabolized primarily by the 3A isoform subfamily of hepatic cytochrome P450.

SubstrateEnzymesProduct
Tiagabine
UnknownDetails
Route of eliminationApproximately 2% of an oral dose of tiagabine is excreted unchanged, with 25% and 63% of the remaining dose excreted into the urine and feces, respectively, primarily as metabolites.
Half life7-9 hours
Clearance
  • 109 mL/min [Healthy subjects]
Toxicitymptoms most often accompanying tiagabine overdose, alone or in combination with other drugs, have included: seizures including status epilepticus in patients with and without underlying seizure disorders, nonconvulsive status epilepticus, coma, ataxia, confusion, somnolence, drowsiness, impaired speech, agitation, lethargy, myoclonus, spike wave stupor, tremors, disorientation, vomiting, hostility, and temporary paralysis. Respiratory depression was seen in a number of patients, including children, in the context of seizures.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9603
Blood Brain Barrier+0.9382
Caco-2 permeable-0.5368
P-glycoprotein substrateSubstrate0.6504
P-glycoprotein inhibitor INon-inhibitor0.6879
P-glycoprotein inhibitor IINon-inhibitor0.9609
Renal organic cation transporterInhibitor0.5083
CYP450 2C9 substrateNon-substrate0.7898
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateNon-substrate0.5299
CYP450 1A2 substrateInhibitor0.5784
CYP450 2C9 inhibitorNon-inhibitor0.6727
CYP450 2D6 inhibitorNon-inhibitor0.812
CYP450 2C19 inhibitorNon-inhibitor0.5865
CYP450 3A4 inhibitorNon-inhibitor0.9568
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7011
Ames testNon AMES toxic0.7455
CarcinogenicityNon-carcinogens0.9505
BiodegradationReady biodegradable0.5139
Rat acute toxicity2.5164 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5333
hERG inhibition (predictor II)Non-inhibitor0.8672
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Cephalon inc
Packagers
Dosage forms
FormRouteStrength
Tabletoral12 mg/1
Tabletoral4 mg/1
Tablet, film coatedoral12 mg/1
Tablet, film coatedoral16 mg/1
Tablet, film coatedoral2 mg/1
Tablet, film coatedoral4 mg/1
Prices
Unit descriptionCostUnit
Gabitril 16 mg tablet12.53USD tablet
Gabitril 12 mg tablet6.4USD tablet
Gabitril 2 mg tablet4.89USD tablet
Gabitril 4 mg tablet3.9USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5010090 No1994-09-302011-09-30Us
US5866590 No1996-04-292016-04-29Us
US5958951 No1997-06-102017-06-10Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP2.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0211 mg/mLALOGPS
logP4.98ALOGPS
logP2.6ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)4.14ChemAxon
pKa (Strongest Basic)9.26ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area40.54 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity115.32 m3·mol-1ChemAxon
Polarizability41.7 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Henning Petersen, Peter Nielsen, Michael Cain, Subhash Patel, “Crystalline Tiagabine monohydrate, its preparation and use.” U.S. Patent US5354760, issued April, 1991.

US5354760
General ReferencesNot Available
External Links
ATC CodesN03AG06
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (251 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AprepitantThe serum concentration of Tiagabine can be increased when it is combined with Aprepitant.
AzelastineTiagabine may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
BaclofenThe risk or severity of adverse effects can be increased when Baclofen is combined with Tiagabine.
BexaroteneThe serum concentration of Tiagabine can be decreased when it is combined with Bexarotene.
BosentanThe serum concentration of Tiagabine can be decreased when it is combined with Bosentan.
BrimonidineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of Tiagabine.
BuprenorphineTiagabine may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.
ConivaptanThe serum concentration of Tiagabine can be increased when it is combined with Conivaptan.
DabrafenibThe serum concentration of Tiagabine can be decreased when it is combined with Dabrafenib.
DasatinibThe serum concentration of Tiagabine can be increased when it is combined with Dasatinib.
DeferasiroxThe serum concentration of Tiagabine can be decreased when it is combined with Deferasirox.
DoxylamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of Tiagabine.
DronabinolDronabinol may increase the central nervous system depressant (CNS depressant) activities of Tiagabine.
DroperidolDroperidol may increase the central nervous system depressant (CNS depressant) activities of Tiagabine.
EthanolTiagabine may increase the central nervous system depressant (CNS depressant) activities of Ethanol.
FluconazoleThe metabolism of Tiagabine can be decreased when combined with Fluconazole.
FosaprepitantThe serum concentration of Tiagabine can be increased when it is combined with Fosaprepitant.
Fusidic AcidThe serum concentration of Tiagabine can be increased when it is combined with Fusidic Acid.
HydrocodoneTiagabine may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
HydroxyzineHydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Tiagabine.
IdelalisibThe serum concentration of Tiagabine can be increased when it is combined with Idelalisib.
IvacaftorThe serum concentration of Tiagabine can be increased when it is combined with Ivacaftor.
LorazepamThe risk or severity of adverse effects can be increased when Lorazepam is combined with Tiagabine.
LuliconazoleThe serum concentration of Tiagabine can be increased when it is combined with Luliconazole.
Magnesium SulfateMagnesium Sulfate may increase the central nervous system depressant (CNS depressant) activities of Tiagabine.
MefloquineThe therapeutic efficacy of Tiagabine can be decreased when used in combination with Mefloquine.
MethotrimeprazineTiagabine may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.
MetyrosineTiagabine may increase the sedative activities of Metyrosine.
MianserinThe therapeutic efficacy of Tiagabine can be decreased when used in combination with Mianserin.
MifepristoneThe serum concentration of Tiagabine can be increased when it is combined with Mifepristone.
MinocyclineMinocycline may increase the central nervous system depressant (CNS depressant) activities of Tiagabine.
MirtazapineTiagabine may increase the central nervous system depressant (CNS depressant) activities of Mirtazapine.
MitotaneThe serum concentration of Tiagabine can be decreased when it is combined with Mitotane.
NabiloneNabilone may increase the central nervous system depressant (CNS depressant) activities of Tiagabine.
NelfinavirThe metabolism of Tiagabine can be decreased when combined with Nelfinavir.
NetupitantThe serum concentration of Tiagabine can be increased when it is combined with Netupitant.
OrlistatThe serum concentration of Tiagabine can be decreased when it is combined with Orlistat.
OrphenadrineTiagabine may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
PalbociclibThe serum concentration of Tiagabine can be increased when it is combined with Palbociclib.
ParaldehydeTiagabine may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
ParoxetineThe risk or severity of adverse effects can be increased when Tiagabine is combined with Paroxetine.
PerampanelPerampanel may increase the central nervous system depressant (CNS depressant) activities of Tiagabine.
PhenytoinThe metabolism of Tiagabine can be increased when combined with Phenytoin.
PramipexoleTiagabine may increase the sedative activities of Pramipexole.
RopiniroleTiagabine may increase the sedative activities of Ropinirole.
RotigotineTiagabine may increase the sedative activities of Rotigotine.
RufinamideThe risk or severity of adverse effects can be increased when Rufinamide is combined with Tiagabine.
SiltuximabThe serum concentration of Tiagabine can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Tiagabine can be increased when it is combined with Simeprevir.
Sodium oxybateSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Tiagabine.
St. John's WortThe serum concentration of Tiagabine can be decreased when it is combined with St. John's Wort.
StiripentolThe serum concentration of Tiagabine can be increased when it is combined with Stiripentol.
SuvorexantTiagabine may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.
TapentadolTapentadol may increase the central nervous system depressant (CNS depressant) activities of Tiagabine.
ThalidomideTiagabine may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
TocilizumabThe serum concentration of Tiagabine can be decreased when it is combined with Tocilizumab.
ZolpidemTiagabine may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Neurotransmitter:sodium symporter activity
Specific Function:
Terminates the action of GABA by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A1
Uniprot ID:
P30531
Molecular Weight:
67073.0 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Pollack MH, Roy-Byrne PP, Van Ameringen M, Snyder H, Brown C, Ondrasik J, Rickels K: The selective GABA reuptake inhibitor tiagabine for the treatment of generalized anxiety disorder: results of a placebo-controlled study. J Clin Psychiatry. 2005 Nov;66(11):1401-8. [PubMed:16420077 ]
  3. Sheehan DV, Sheehan KH, Raj BA, Janavs J: An open-label study of tiagabine in panic disorder. Psychopharmacol Bull. 2007;40(3):32-40. [PubMed:18007567 ]
  4. Foster AC, Kemp JA: Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17. Epub 2005 Dec 22. [PubMed:16377242 ]
  5. Sunol C, Babot Z, Cristofol R, Sonnewald U, Waagepetersen HS, Schousboe A: A possible role of the non-GAT1 GABA transporters in transfer of GABA from GABAergic to glutamatergic neurons in mouse cerebellar neuronal cultures. Neurochem Res. 2010 Sep;35(9):1384-90. doi: 10.1007/s11064-010-0196-1. Epub 2010 May 30. [PubMed:20512624 ]
  6. Henjum S, Hassel B: High-affinity GABA uptake and GABA-metabolizing enzymes in pig forebrain white matter: a quantitative study. Neurochem Int. 2007 Jan;50(2):365-70. Epub 2006 Oct 27. [PubMed:17069932 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on July 25, 2016 01:53