Tiagabine (T3D2926)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (4)XML
Targets (4)
Record Information
Version2.0
Creation Date2009-07-21 20:27:55 UTC
Update Date2014-12-24 20:25:53 UTC
Accession NumberT3D2926
Identification
Common NameTiagabine
ClassSmall Molecule
DescriptionTiagabine 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.
Compound Type
  • Amine
  • Anticonvulsant
  • Drug
  • GABA Agonist
  • Metabolite
  • Neuroprotective Agent
  • Neurotransmitter Uptake Inhibitor
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
Gabitril
Tiagabina
Tiagabinum
Chemical FormulaC20H25NO2S2
Average Molecular Mass375.548 g/mol
Monoisotopic Mass375.133 g/mol
CAS Registry Number115103-54-3
IUPAC Name(3R)-1-[4,4-bis(3-methylthiophen-2-yl)but-3-en-1-yl]piperidine-3-carboxylic acid
Traditional Nametiagabine
SMILES[H][C@]1(CCCN(CCC=C(C2=C(C)C=CS2)C2=C(C)C=CS2)C1)C(O)=O
InChI IdentifierInChI=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
InChI KeyInChIKey=PBJUNZJWGZTSKL-MRXNPFEDSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as piperidinecarboxylic acids. Piperidinecarboxylic acids 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
  • Thiophene
  • Heteroaromatic compound
  • Amino acid or derivatives
  • Tertiary amine
  • Amino acid
  • Tertiary aliphatic amine
  • Carboxylic acid derivative
  • Carboxylic acid
  • Monocarboxylic acid or derivatives
  • Azacycle
  • Organic oxygen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Amine
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Carbonyl group
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility2.11e-02 g/L
LogP2.6
Predicted Properties
PropertyValueSource
Water Solubility0.021 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity115.32 m³·mol⁻¹ChemAxon
Polarizability41.7 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-006x-9421000000-a3d6cacc1c1eda797cdc2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00e9-9141000000-ad3f282e81f21efc67a42017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-004j-1769000000-3559976e948cc2135c8c2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-004j-0984000000-a978c5e709fb0da0ceca2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Negativesplash10-004i-0901000000-f4977b5cba740f9bf1462021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0029000000-c5f87e6c22eea721b9052016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a6s-1298000000-59e359809fb473d67bb32016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4j-4190000000-98420f8a2019b820d7412016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-1009000000-bd93b21b33d14728f6cb2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-6119000000-718202039949c898877e2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a5a-9011000000-8572588cb43983c9c7992016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0019000000-85f99d6f70a9fbf994d22021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4j-0049000000-db812ecf5f7fb19759262021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0002-9032000000-b4c12faa49251f4425b02021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0009000000-75b21c9b910e4d5d90b62021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-0039000000-b8393c7a9d1fdd48a1a22021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00r2-5294000000-26284b1d5f7adf9241ff2021-10-11View Spectrum
Toxicity Profile
Route of ExposureOral. Tiagabine is nearly completely absorbed (>95%).
Mechanism of ToxicityThough 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.
MetabolismTiagabine is likely metabolized primarily by the 3A isoform subfamily of hepatic cytochrome P450. Route of Elimination: Approximately 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 Life: 7-9 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of partial seizures
Minimum Risk LevelNot Available
Health EffectsRespiratory depression was seen in a number of patients, including children, in the context of seizures. May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.
SymptomsSymptoms 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.
TreatmentThere is no specific antidote for overdose with Tiagabine. If indicated, elimination of unabsorbed drug should be achieved by emesis or gastric lavage; usual precautions should be observed to maintain the airway. General supportive care of the patient is indicated including monitoring of vital signs and observation of clinical status of the patient. Since tiagabine is mostly metabolized by the liver and is highly protein bound, dialysis is unlikely to be beneficial. (2)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00906
HMDB IDHMDB15042
PubChem Compound ID60648
ChEMBL IDCHEMBL1027
ChemSpider ID54661
KEGG IDC07503
UniProt IDNot Available
OMIM ID
ChEBI ID222170
BioCyc IDNot Available
CTD IDNot Available
Stitch IDTiagabine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkTiagabine
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.

MSDST3D2926.pdf
General References
  1. Drugs.com [Link]
  2. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. 4-aminobutyrate aminotransferase, mitochondrial
General Function:
Succinate-semialdehyde dehydrogenase binding
Specific Function:
Catalyzes the conversion of gamma-aminobutyrate and L-beta-aminoisobutyrate to succinate semialdehyde and methylmalonate semialdehyde, respectively. Can also convert delta-aminovalerate and beta-alanine.
Gene Name:
ABAT
Uniprot ID:
P80404
Molecular Weight:
56438.405 Da
References
  1. Sills GJ, Butler E, Thompson GG, Brodie MJ: Vigabatrin and tiagabine are pharmacologically different drugs. A pre-clinical study. Seizure. 1999 Oct;8(7):404-11. [10600581 ]
  2. Czuczwar SJ: [GABA-ergic system and antiepileptic drugs]. Neurol Neurochir Pol. 2000;34 Suppl 1:13-20. [10768141 ]
  3. Czuczwar SJ: [GABA-ergic system and antiepileptic drugs]. Neurol Neurochir Pol. 1999 Nov-Dec;33(6):1373-80. [10791039 ]
  4. Deisz RA: Cellular mechanisms of pharmacoresistance in slices from epilepsy surgery. Novartis Found Symp. 2002;243:186-99; discussion 199-206, 231-5. [11990776 ]
  5. Costa C, Leone G, Saulle E, Pisani F, Bernardi G, Calabresi P: Coactivation of GABA(A) and GABA(B) receptor results in neuroprotection during in vitro ischemia. Stroke. 2004 Feb;35(2):596-600. Epub 2004 Jan 15. [14726544 ]
Target Details
2. Sodium- and chloride-dependent GABA transporter 1
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.01698 uMNot AvailableBindingDB 50039251
IC500.07 uMNot AvailableBindingDB 50039251
IC500.28 uMNot AvailableBindingDB 50039251
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Dhar TG, Borden LA, Tyagarajan S, Smith KE, Branchek TA, Weinshank RL, Gluchowski C: Design, synthesis and evaluation of substituted triarylnipecotic acid derivatives as GABA uptake inhibitors: identification of a ligand with moderate affinity and selectivity for the cloned human GABA transporter GAT-3. J Med Chem. 1994 Jul 22;37(15):2334-42. [8057281 ]
  3. Zheng J, Wen R, Luo X, Lin G, Zhang J, Xu L, Guo L, Jiang H: Design, synthesis, and biological evaluation of the N-diarylalkenyl-piperidinecarboxylic acid derivatives as GABA uptake inhibitors (I). Bioorg Med Chem Lett. 2006 Jan 1;16(1):225-7. Epub 2005 Oct 21. [16246548 ]
  4. Pizzi DA, Leslie CP, Di Fabio R, Seri C, Bernasconi G, Squaglia M, Carnevale G, Falchi A, Greco E, Mangiarini L, Negri M: Stereospecific synthesis and structure-activity relationships of unsymmetrical 4,4-diphenylbut-3-enyl derivatives of nipecotic acid as GAT-1 inhibitors. Bioorg Med Chem Lett. 2011 Jan 1;21(1):602-5. doi: 10.1016/j.bmcl.2010.09.025. Epub 2010 Sep 15. [21134748 ]
Target Details
3. Sodium- and chloride-dependent GABA transporter 3
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:
SLC6A11
Uniprot ID:
P48066
Molecular Weight:
70605.145 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50917 uMNot AvailableBindingDB 50039251
References
  1. Dhar TG, Borden LA, Tyagarajan S, Smith KE, Branchek TA, Weinshank RL, Gluchowski C: Design, synthesis and evaluation of substituted triarylnipecotic acid derivatives as GABA uptake inhibitors: identification of a ligand with moderate affinity and selectivity for the cloned human GABA transporter GAT-3. J Med Chem. 1994 Jul 22;37(15):2334-42. [8057281 ]
Target Details
4. Sodium- and chloride-dependent betaine transporter
General Function:
Neurotransmitter:sodium symporter activity
Specific Function:
Transports betaine and GABA. May have a role in regulation of GABAergic transmission in the brain through the reuptake of GABA into presynaptic terminals, as well as in osmotic regulation.
Gene Name:
SLC6A12
Uniprot ID:
P48065
Molecular Weight:
69367.655 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC501670 uMNot AvailableBindingDB 50039251
References
  1. Dhar TG, Borden LA, Tyagarajan S, Smith KE, Branchek TA, Weinshank RL, Gluchowski C: Design, synthesis and evaluation of substituted triarylnipecotic acid derivatives as GABA uptake inhibitors: identification of a ligand with moderate affinity and selectivity for the cloned human GABA transporter GAT-3. J Med Chem. 1994 Jul 22;37(15):2334-42. [8057281 ]