Tiagabine (CED0005643)

Record Information

Version

1.0

Creation Date

2009-07-21 20:27:55 UTC

Update Date

2026-05-14 16:52:27 UTC

SynCED ID

CED0005643

Secondary Accession Numbers

CHEM002298
T3D2926

Identification

Common Name

Tiagabine

Class

Small Molecule

Description

Tiagabine is an exogenous organic compound with the formula C20H25NO2S2 and an average molecular weight of 375.55 g/mol. It exists as a solid at room temperature. Tiagabine belongs to the piperidinecarboxylic acids and derivatives, a subclass of piperidines within the organic compounds. The compound is found in several recorded sources, including antiepileptics within healthcare, pharmaceuticals, and veterinary products, as well as electrically stimulated smoking devices and other smoking requisites such as cigar cigarettes in household cleaning and consumer products. The recorded route of exposure is oral. Tiagabine has four recorded protein targets: the mitochondrial 4-aminobutyrate aminotransferase (ABAT), the sodium- and chloride-dependent GABA transporter 1 (SLC6A1), the sodium- and chloride-dependent GABA transporter 3 (SLC6A11), and the sodium- and chloride-dependent betaine transporter (SLC6A12). 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.

Contaminant Type

Amine
Anticonvulsant
Drug
GABA Agonist
Human Neurotoxin
Metabolite
Neuroprotective Agent
Neurotransmitter Uptake Inhibitor
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
(-)-(R)-1-(4,4-Bis(3-methyl-2-thienyl)-3-butenyl)nipecotic acid	ChEBI
(-)-(R)-1-[4,4-Bis(3-methyl-2-thienyl)-3-butenyl]nipecotic acid	ChEBI
(R)-(-)-1-[4,4-Bis(3-methyl-2-thienyl)-3-butenyl]nipecotic acid	ChEBI
(R)-Tiagabine	ChEBI
Tiagabina	ChEBI
Tiagabinum	ChEBI
Gabitril	Kegg
(-)-(R)-1-(4,4-Bis(3-methyl-2-thienyl)-3-butenyl)nipecotate	Generator
(-)-(R)-1-[4,4-Bis(3-methyl-2-thienyl)-3-butenyl]nipecotate	Generator
(R)-(-)-1-[4,4-Bis(3-methyl-2-thienyl)-3-butenyl]nipecotate	Generator
Tiagabine, (S)-isomer	HMDB
(R)-(4,4-Bis(3-methyl-2-thienyl)-3-butenyl)-3-piperidinecarboxylic acid, hydrochloride	HMDB
N-(4,4-Di(3-methylthien-2-yl)but-3-enyl)nipecotic acid	HMDB
Tiagabine hydrochloride	HMDB

Chemical Formula

C₂₀H₂₅NO₂S₂

Average Molecular Mass

375.548 g/mol

Monoisotopic Mass

375.133 g/mol

CAS Registry Number

115103-54-3

IUPAC Name

(3R)-1-[4,4-bis(3-methylthiophen-2-yl)but-3-en-1-yl]piperidine-3-carboxylic acid

Traditional Name

tiagabine

SMILES

CC1=C(SC=C1)C(=CCCN1CCC[C@H](C1)C(O)=O)C1=C(C)C=CS1

InChI Identifier

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

InChI Key

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.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Piperidines

Sub Class

Piperidinecarboxylic acids and derivatives

Direct Parent

Piperidinecarboxylic 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 Framework

Aromatic heteromonocyclic compounds

External Descriptors

tertiary amino compound (CHEBI:9586 )
thiophenes (CHEBI:9586 )
piperidinemonocarboxylic acid (CHEBI:9586 )
beta-amino acid (CHEBI:9586 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Applications

Not Available

Biological Roles

antioxidant (PMC11641357 )?

Chemical Roles

Not Available

Organoleptic Effects

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	Not Available
Boiling Point	Not Available
Solubility	2.11e-02 g/L

Predicted Properties

Property	Value	Source
Water Solubility	0.021 g/L	ALOGPS
logP	4.98	ALOGPS
logP	2.6	ChemAxon
logS	-4.2	ALOGPS
pKa (Strongest Acidic)	4.14	ChemAxon
pKa (Strongest Basic)	9.26	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	40.54 Å²	ChemAxon
Rotatable Bond Count	6	ChemAxon
Refractivity	115.32 m³·mol⁻¹	ChemAxon
Polarizability	41.7 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum	splash10-006x-9421000000-a3d6cacc1c1eda797cdc	Not Available	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum	splash10-00e9-9141000000-ad3f282e81f21efc67a4	Not Available	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum	Not Available	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-004j-1769000000-3559976e948cc2135c8c	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-004j-0984000000-a978c5e709fb0da0ceca	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-004i-0901000000-f4977b5cba740f9bf146	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-004i-0029000000-c5f87e6c22eea721b905	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0a6s-1298000000-59e359809fb473d67bb3	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0a4j-4190000000-98420f8a2019b820d741	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-00di-1009000000-bd93b21b33d14728f6cb	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-001i-6119000000-718202039949c898877e	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0a5a-9011000000-8572588cb43983c9c799	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-004i-0019000000-85f99d6f70a9fbf994d2	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0a4j-0049000000-db812ecf5f7fb1975926	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0002-9032000000-b4c12faa49251f4425b0	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-00di-0009000000-75b21c9b910e4d5d90b6	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-00di-0039000000-b8393c7a9d1fdd48a1a2	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-00r2-5294000000-26284b1d5f7adf9241ff	Not Available	View Spectrum

Toxicity Profile

Toxicity Values

Toxicity Value	Organism	Dose Descriptor	Route of Exposure	Predicted or Experimental	Toxicity Rating	Reference
1004.0 Log mg/kg [560:1800]	Rat	LD50	oral	predicted	Not Available	Not Available

Toxicity / Toxin Class

Not Available

Mechanism of Toxicity

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.

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Minimum Risk Level

Not Available

Symptoms

Symptoms 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.

Treatment

There 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)

Health Effects

Health Effect	Relationship	Direction	Description	Reference
seizure	Not Available	Not Available	Not Available	PMC6249062
epilepsy	Not Available	Not Available	A brain disease that is characterized by the occurrance of at least two unprovoked seizures resulting from a persistent epileptogenic abnormality of the brain that is able to spontaneously generate paroxysmal activity and typically manifested by sudden brief episodes of altered or diminished consciousness, involuntary movements, or convulsions. (DO)	PMC6365001 , PMC3996097

Exposure Sources

Source ID	Source	Sector	Reference
CEDs000371	Antiepileptics?Antiepileptics are a class of synthetic drugs used primarily to manage seizure disorders.	Healthcare, pharmaceuticals & veterinary products	Not Available
CEDs000518	Electrically Stimulated Smoking Devices?Electrically stimulated smoking devices, commonly known as e-cigarettes or vape pens, utilize electrical components to heat a liquid solution, often containing nicotine, flavorings, and other additives, to produce an aerosol for inhalation.	Electrical & Electronic Equipment	PubChem
CEDs000556	Cigar Cigarettes?Cigar cigarettes are a source of synthetic chemical contamination due to the combustion of various tobacco blends and additives.	Household cleaning & consumer products	PubChem
CEDs000560	Other Smoking Requisites?Other smoking requisites, including items such as lighters, matches, and rolling papers, can introduce synthetic chemical contamination through various components and additives.	Household cleaning & consumer products	PubChem
CEDs000569	Tobacco Smoke Filters?Tobacco smoke filters are designed to reduce the inhalation of harmful substances in cigarette smoke, including tar and other particulate matter.	Household cleaning & consumer products	PubChem
CEDs000580	Manufacture Preparation Of Tobacco Products?The manufacture and preparation of tobacco products involve various processes that can result in the introduction of synthetic chemicals into the environment.	Industrial manufacturing & chemical processing	PubChem
CEDs000611	Anti Perspirants Or Body Deoderants?Antiperspirants and body deodorants commonly contain synthetic chemicals such as aluminum compounds, parabens, and synthetic fragrances.	Personal care & cosmetics	PubChem
CEDs000632	Apparel?Apparel production often involves the use of various synthetic chemicals, including dyes, finishing agents, and preservatives.	Textiles, leather & furnishings	PubChem
CEDs000671	Airplanes And Helicopters?Airplanes and helicopters are significant sources of synthetic chemical contamination primarily through the use of aviation fuels, lubricants, and de-icing agents.	Aviation & Aerospace	PubChem
CEDs000685	Ceramics?Ceramics can be a source of synthetic chemical contamination through various additives and processing agents used in their production.	Building & Construction	PubChem
CEDs000696	Nanotechnology?Nanotechnology involves the manipulation of materials at the molecular or atomic level, typically within the range of 1 to 100 nanometers.	Industrial manufacturing & chemical processing	PubChem
CEDs000735	Explosives?Explosives are chemical compounds or mixtures designed to undergo rapid decomposition, releasing energy in the form of gas and heat.	Defense & military infrastructure	PubChem
CEDs000741	Pigment Pastes?Pigment pastes are concentrated dispersions of pigments used to impart color and properties to materials.	Paper, pulp & fiber products	PubChem

Pathways

1 pathwayPathway Source: PathBank

Tiagabine Drug Metabolism Action Pathway

Targets

Structure	Protein	UniProt ID	Organism	Relationship	Details
Click to view 3D structure	GABA transporter 3	P31649	Mus musculus	Predicted (SEA)	Prediction Confidence Score 0.336 Applicability Domain 0.429 Statistical Significance 1.20e-04 Supporting Reference Compounds 12 E-value 0.934191
Click to view 3D structure	Sodium- and chloride-dependent GABA transporter 3	P48066	Humans	Predicted (SEA)	Prediction Confidence Score 0.328 Applicability Domain 0.444 Statistical Significance 1.10e-04 Supporting Reference Compounds 11 E-value 0.856341
Click to view 3D structure	Cytochrome P450 3A4	P08684	Humans	Predicted (SEA)	Prediction Confidence Score 0.313 Applicability Domain 0.6 Statistical Significance 0.1215 Supporting Reference Compounds 1538 E-value 946.102
Click to view 3D structure	Cytochrome P450 2C9	P11712	Humans	Predicted (SEA)	Prediction Confidence Score 0.311 Applicability Domain 0.6 Statistical Significance 0.1008 Supporting Reference Compounds 1245 E-value 784.487
Click to view 3D structure	Cytochrome P450 2C19	P33261	Humans	Predicted (SEA)	Prediction Confidence Score 0.303 Applicability Domain 0.6 Statistical Significance 0.0636 Supporting Reference Compounds 825 E-value 494.965
Click to view 3D structure	Cytochrome P450 1A2	P05177	Humans	Predicted (SEA)	Prediction Confidence Score 0.298 Applicability Domain 0.6 Statistical Significance 0.0773 Supporting Reference Compounds 793 E-value 601.93
Click to view 3D structure	Sigma non-opioid intracellular receptor 1	Q9R0C9	Rattus norvegicus	Predicted (SEA)	Prediction Confidence Score 0.293 Applicability Domain 0.322 Statistical Significance 0.0267 Supporting Reference Compounds 207 E-value 207.78
Click to view 3D structure	D(2) dopamine receptor	P61169	Rat	Predicted (SEA)	Prediction Confidence Score 0.283 Applicability Domain 0.297 Low confidence Statistical Significance 0.0756 Supporting Reference Compounds 528 E-value 588.229
Click to view 3D structure	D(2) dopamine receptor	P14416	Humans	Predicted (SEA)	Prediction Confidence Score 0.272 Applicability Domain 0.29 Low confidence Statistical Significance 0.1699 Supporting Reference Compounds 1103 E-value 1322.35
Click to view 3D structure	Sphingosine 1-phosphate receptor 5	Q9H228	Humans	Predicted (SEA)	Prediction Confidence Score 0.27 Applicability Domain 0.299 Low confidence Statistical Significance 0.0167 Supporting Reference Compounds 49 E-value 129.93
Click to view 3D structure	Sigma non-opioid intracellular receptor 1	Q99720	Humans	Predicted (SEA)	Prediction Confidence Score 0.269 Applicability Domain 0.281 Low confidence Statistical Significance 0.126 Supporting Reference Compounds 562 E-value 980.745
Click to view 3D structure	5-hydroxytryptamine receptor 1A	P19327	Rattus norvegicus	Predicted (SEA)	Prediction Confidence Score 0.268 Applicability Domain 0.281 Low confidence Statistical Significance 0.1141 Supporting Reference Compounds 541 E-value 888.182
Click to view 3D structure	D(3) dopamine receptor	P35462	Humans	Predicted (SEA)	Prediction Confidence Score 0.266 Applicability Domain 0.281 Low confidence Statistical Significance 0.1644 Supporting Reference Compounds 861 E-value 1280.07
Click to view 3D structure	D(4) dopamine receptor	P21917	Humans	Predicted (SEA)	Prediction Confidence Score 0.266 Applicability Domain 0.281 Low confidence Statistical Significance 0.13 Supporting Reference Compounds 524 E-value 1012.04
Click to view 3D structure	Kelch-like ECH-associated protein 1	Q9Z2X8	Mus musculus	Predicted (SEA)	Prediction Confidence Score 0.26 Applicability Domain 0.26 Low confidence Statistical Significance 0.0012 Supporting Reference Compounds 1 E-value 9.18621
Click to view 3D structure	Sphingosine 1-phosphate receptor 1	P21453	Humans	Predicted (SEA)	Prediction Confidence Score 0.259 Applicability Domain 0.27 Low confidence Statistical Significance 0.0379 Supporting Reference Compounds 126 E-value 295.438
Click to view 3D structure	Histamine H3 receptor	Q9Y5N1	Humans	Predicted (SEA)	Prediction Confidence Score 0.259 Applicability Domain 0.294 Low confidence Statistical Significance 0.0908 Supporting Reference Compounds 294 E-value 707.027
Click to view 3D structure	D(2) dopamine receptor	P20288	Bos taurus	Predicted (SEA)	Prediction Confidence Score 0.257 Applicability Domain 0.281 Low confidence Statistical Significance 0.0278 Supporting Reference Compounds 72 E-value 216.421
Click to view 3D structure	Mitogen-activated protein kinase 8	P45983	Humans	Predicted (SEA)	Prediction Confidence Score 0.255 Applicability Domain 0.27 Low confidence Statistical Significance 0.3029 Supporting Reference Compounds 782 E-value 2357.82
Click to view 3D structure	Tyrosine-protein kinase JAK3	P52333	Humans	Predicted (SEA)	Prediction Confidence Score 0.255 Applicability Domain 0.27 Low confidence Statistical Significance 0.3275 Supporting Reference Compounds 961 E-value 2549.8
Click to view 3D structure	Sodium- and chloride-dependent GABA transporter 1	P30531	Humans	Predicted (SEA)	Prediction Confidence Score 0.698 Applicability Domain 1.0 Statistical Significance 1.00e-05 Supporting Reference Compounds 8 E-value 0.0778492
Click to view 3D structure	Sodium- and chloride-dependent GABA transporter 1	P31648	Mus musculus	Predicted (SEA)	Prediction Confidence Score 0.643 Applicability Domain 1.0 Statistical Significance 1.00e-05 Supporting Reference Compounds 17 E-value 0.0778492
Click to view 3D structure	Sodium- and chloride-dependent GABA transporter 1	P23978	Rattus norvegicus	Predicted (SEA)	Prediction Confidence Score 0.588 Applicability Domain 1.0 Statistical Significance 1.00e-05 Supporting Reference Compounds 5 E-value 0.0778492
Click to view 3D structure	GABA transporter 4	P31650	Mus musculus	Predicted (SEA)	Prediction Confidence Score 0.402 Applicability Domain 0.429 Statistical Significance 1.90e-04 Supporting Reference Compounds 21 E-value 1.47914
Click to view 3D structure	GABA transporter 2	P31651	Mus musculus	Predicted (SEA)	Prediction Confidence Score 0.392 Applicability Domain 1.0 Statistical Significance 1.10e-04 Supporting Reference Compounds 13 E-value 0.856341
Click to view 3D structure	4-aminobutyrate aminotransferase, mitochondrial	P80404	Humans	Known	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.
Click to view 3D structure	Sodium- and chloride-dependent GABA transporter 1	P30531	Humans	Known	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.
Click to view 3D structure	Sodium- and chloride-dependent GABA transporter 3	P48066	Humans	Known	Not Available
Click to view 3D structure	Sodium- and chloride-dependent betaine transporter	P48065	Humans	Known	Not Available

Concentrations

Not Available

External Links

DrugBank ID

DB00906

HMDB ID

HMDB0015042

FooDB ID

Not Available

Phenol Explorer ID

Not Available

KNApSAcK ID

Not Available

BiGG ID

Not Available

BioCyc ID

Not Available

METLIN ID

Not Available

PDB ID

Not Available

Wikipedia Link

Chemspider ID

ChEBI ID

PubChem Compound ID

Kegg Compound ID

YMDB ID

Not Available

ECMDB ID

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.

MSDS

Not Available

General References

Drugs.com http://www.drugs.com/cons/Tiagabine.html
RxList: The Internet Drug Index (2009). http://www.rxlist.com/

Tiagabine (CED0005643)

Structure for CHEM002298: Tiagabine

Structure