Tiagabine

Tiagabine
Clinical data
Pronunciation	/taɪˈæɡəbiːn/
Trade names	Gabitril
Other names	TGB; A-70569; A70569; ABT-569; ABT569; Abbott 70569; CEP-6671; CEP6671; N 05-0328; NNC 05-0328; NO-050328; NO050328; NO-328; NO328
AHFS/Drugs.com	Monograph
MedlinePlus	a698014
Pregnancy; category	AU: B3; ;
Routes of; administration	Oral
Drug class	GABA reuptake inhibitor; GABA transporter 1 (GAT-1) inhibitor; Anticonvulsant; Hypnotic; Anxiolytic
ATC code	N03AG06 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only); BR: Class C1 (Other controlled substances); CA: ℞-only; UK: POM (Prescription only); US: ℞-only;
Pharmacokinetic data
Bioavailability	90%
Protein binding	96%
Metabolism	CYP3A4, possibly other CYP450 enzymes, glucuronidation
Metabolites	5-Oxotiagabine, others
Onset of action	1–1.5 hours (45 min fasted, 2.5 hours with high-fat meal) (peak)
Elimination half-life	4.5–9.0 hours; Enzyme-induced patients: 2–3 hours
Excretion	Feces: 63%; Urine: 25% (<3% unchanged)
Identifiers
	IUPAC name (−)-(3R)-1-[4,4-bis(3-methyl-2-thienyl)-3-buten-1-yl]-3-piperidinecarboxylic acid;
CAS Number	115103-54-3 ;
PubChem CID	60648;
IUPHAR/BPS	4685;
DrugBank	DB00906 ;
ChemSpider	54661 ;
UNII	Z80I64HMNP;
KEGG	D08588 ;
ChEBI	CHEBI:9586;
ChEMBL	ChEMBL1027 ;
CompTox Dashboard (EPA)	DTXSID5023663 ;
Chemical and physical data
Formula	C20H25NO2S2
Molar mass	375.55 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C(O)[C@H]1CN(CCC1)CC/C=C(/c2sccc2C)c3sccc3C;
	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 ; Key:PBJUNZJWGZTSKL-MRXNPFEDSA-N ;
	(verify)

Tiagabine, sold under the brand name Gabitril, is an anticonvulsant medication which is used in the treatment of epilepsy. It is also used off-label in the treatment of insomnia and anxiety disorders. However, off-label use is discouraged as the drug has been associated with new-onset seizures in people without epilepsy. Tiagabine is taken orally.

Side effects of tiagabine include dizziness, asthenia, non-specific nervousness, muscle tremors, diarrhea, depression, and emotional lability. The drug acts as a selective GABA transporter 1 (GAT-1) blocker or GABA reuptake inhibitor, and hence acts as an indirect GABA receptor agonist, increasing GABAergic signaling in the brain. It may increase activation of both GABA_A and GABA_B receptors. The effects of tiagabine on sleep resemble those of GABA_A receptor agonists like gaboxadol and muscimol, primarily enhancing slow wave sleep, and differ from those of GABA_A receptor positive allosteric modulators like benzodiazepines and Z drugs. The drug's elimination half-life is 4.5 to 9 hours, but can be shorter in people taking enzyme-inducing anticonvulsants.

Tiagabine was discovered in 1988 and was introduced for medical use in 1997. Generic formulations have become available. The drug is not a controlled substance in the United States.