Identification

Name
Tiagabine
Accession Number
DB00906  (APRD00344)
Type
Small Molecule
Groups
Approved, Investigational
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
  • Tiagabina
  • Tiagabinum
Product Ingredients
IngredientUNIICASInChI Key
Tiagabine hydrochlorideDQH6T6D8OY145821-59-6YUKARLAABCGMCN-PKLMIRHRSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
GabitrilTablet4 mg/1OralLake Erie Medical &Surgical Supply Dba Quality Care Products Llc2011-11-152014-12-31Us
GabitrilTablet12 mg/1OralStat Rx USA1997-11-03Not applicableUs63459 0412 30 nlmimage10 8b2d45da
GabitrilTablet, film coated4 mg/1OralCephalon, Inc.2001-04-01Not applicableUs63459 0404 30 nlmimage10 a72d538a
GabitrilTablet, film coated4 mg/1OralCarilion Materials Management2001-04-01Not applicableUs68151 423520180907 15195 1f8l9jv
GabitrilTablet, film coated16 mg/1OralCephalon, Inc.2001-04-01Not applicableUs63459 0416 30 nlmimage10 8f2d47ea
GabitrilTablet, film coated2 mg/1OralCephalon, Inc.2001-04-01Not applicableUs63459 0402 30 nlmimage10 ab2d559a
GabitrilTablet2 mg/1OralPhysicians Total Care, Inc.2004-08-312011-06-30Us
GabitrilTablet, film coated12 mg/1OralCephalon, Inc.2001-04-01Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Tiagabine HydrochlorideTablet, film coated4 mg/1OralSun Pharmaceutical Industries, Inc.2011-11-04Not applicableUs
Tiagabine HydrochlorideTablet4 mg/1OralAmneal Pharmaceuticals2017-12-08Not applicableUs
Tiagabine HydrochlorideTablet, film coated2 mg/1OralCima Labs Inc.2012-12-212017-05-31Us55253 0600 30 nlmimage10 c635637b
Tiagabine HydrochlorideTablet12 mg/1OralWilshire Pharmaceuticals, Inc.2018-06-01Not applicableUs
Tiagabine HydrochlorideTablet2 mg/1OralWilshire Pharmaceuticals, Inc.2018-06-01Not applicableUs
Tiagabine HydrochlorideTablet, film coated4 mg/1OralTeva2016-06-03Not applicableUs
Tiagabine HydrochlorideTablet16 mg/1OralAmneal Pharmaceuticals2017-12-08Not applicableUs
Tiagabine HydrochlorideTablet2 mg/1OralAmneal Pharmaceuticals2017-12-08Not applicableUs
Tiagabine HydrochlorideTablet, film coated2 mg/1OralSun Pharmaceutical Industries, Inc.2011-11-04Not applicableUs
Tiagabine HydrochlorideTablet, film coated16 mg/1OralTeva2018-03-09Not applicableUs
International/Other Brands
Gabitril
Categories
UNII
Z80I64HMNP
CAS number
115103-54-3
Weight
Average: 375.548
Monoisotopic: 375.132670429
Chemical Formula
C20H25NO2S2
InChI Key
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[C@H](C1)C(O)=O)C1=C(C)C=CS1

Pharmacology

Indication

For the treatment of partial seizures

Associated Conditions
Pharmacodynamics

Tiagabine 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 action

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.

TargetActionsOrganism
ASodium- and chloride-dependent GABA transporter 1
inhibitor
Human
Absorption

Tiagabine is nearly completely absorbed (>95%).

Volume of distribution
Not Available
Protein binding

96%

Metabolism

Tiagabine 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

Clearance
  • 109 mL/min [Healthy subjects]
Toxicity

mptoms 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Tiagabine.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Tiagabine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Tiagabine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineTiagabine may increase the excretion rate of 3-isobutyl-1-methyl-7H-xanthine which could result in a lower serum level and potentially a reduction in efficacy.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Tiagabine is combined with 3,4-Methylenedioxyamphetamine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Tiagabine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Tiagabine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Tiagabine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Tiagabine is combined with 4-Methoxyamphetamine.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Tiagabine.
Food Interactions
Not 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 References
Not Available
External Links
Human Metabolome Database
HMDB0015042
KEGG Compound
C07503
PubChem Compound
60648
PubChem Substance
46505560
ChemSpider
54661
BindingDB
50368628
ChEBI
9586
ChEMBL
CHEMBL1027
Therapeutic Targets Database
DAP000164
PharmGKB
PA451682
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Tiagabine
ATC Codes
N03AG06 — Tiagabine
FDA label
Download (251 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1TerminatedBasic ScienceAlcohol Dependence1
2CompletedTreatmentCocaine-Related Disorders2
2CompletedTreatmentCocaine-Related Disorders / Opiate Dependence1
2CompletedTreatmentSleep Apnea, Obstructive1
3Active Not RecruitingTreatmentSchizophrenic Disorders1
3CompletedNot AvailableAnxiety Disorders1
3CompletedTreatmentAnxiety Disorders1
3CompletedTreatmentGeneral Anxiety Disorder1
3CompletedTreatmentGeneralized Anxiety Disorder (GAD)2
4CompletedTreatmentEpilepsy, Localization Related1
4CompletedTreatmentSocial Anxiety Disorder (SAD)1

Pharmacoeconomics

Manufacturers
  • Cephalon inc
Packagers
  • Abbott Laboratories Ltd.
  • Cephalon Inc.
  • Diversified Healthcare Services Inc.
  • Heartland Repack Services LLC
  • Innoviant Pharmacy Inc.
  • Nucare Pharmaceuticals Inc.
  • Physician Partners Ltd.
  • Physicians Total Care Inc.
  • Rebel Distributors Corp.
  • Siegfried Ltd.
  • Southwood Pharmaceuticals
  • Stat Rx Usa
Dosage forms
FormRouteStrength
TabletOral12 mg/1
TabletOral2 mg/1
Tablet, film coatedOral4 mg/1
TabletOral16 mg/1
TabletOral4 mg/1
Tablet, film coatedOral12 mg/1
Tablet, film coatedOral16 mg/1
Tablet, film coatedOral2 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)
US5010090No1994-09-302011-09-30Us
US5958951No1997-06-102017-06-10Us
US5866590No1996-04-292016-04-29Us

Properties

State
Solid
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 RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004j-1769000000-3559976e948cc2135c8c

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Piperidines
Sub Class
Piperidinecarboxylic acids and derivatives
Direct Parent
Piperidinecarboxylic acids
Alternative Parents
Thiophenes / Heteroaromatic compounds / Trialkylamines / Amino acids / Monocarboxylic acids and derivatives / Carboxylic acids / Azacyclic compounds / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives
show 1 more
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
show 11 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
tertiary amino compound, thiophenes, piperidinemonocarboxylic acid, beta-amino acid (CHEBI:9586)

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
Uniprot Name
Sodium- and chloride-dependent GABA transporter 1
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
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]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Interactions [Link]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:48