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Tiagabine

Clinical data
Trade names	Gabitril
AHFS/Drugs.com	Monograph
MedlinePlus	a698014
Pregnancy category	B3 (Au), C (U.S.)
Routes of administration	Oral
ATC code	N03AG06 (WHO)
Legal status
Legal status	POM (UK), ℞-only (U.S.)
Pharmacokinetic data
Bioavailability	90%
Protein binding	96%
Metabolism	Hepatic (CYP450 system)
Elimination half-life	7-9 hours
Excretion	Fecal and renal
Identifiers
IUPAC name (R)-1- piperidine-3-carboxylic acid
CAS Number	115103-54-3
PubChem CID	60648
DrugBank	APRD00344
ChemSpider	54661
UNII	Z80I64HMNP
KEGG	D08588
ChEMBL	ChEMBL1027
CompTox Dashboard (EPA)	DTXSID5023663
Chemical and physical data
Formula	C20H25NO2S2
Molar mass	375.55 g/mol g·mol
3D model (JSmol)	Interactive image
SMILES O=C(O)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
(what is this?)  (verify)

Tiagabine (/taɪˈæɡəbiːn/ is an anti-convulsive medication produced by Cephalon and marketed under the brand name Gabitril. The drug was discovered at Novo Nordisk in Denmark in 1988 and was co-developed with Abbott. After a period of co-promotion, Cephalon licensed Tiagabine from Abbott/Novo and now is the exclusive producer. The medication is also used in the treatment of panic disorder, as are a few other anticonvulsants.

Indications

Tiagabine is approved by U.S. Food and Drug Administration (FDA) as an adjunctive treatment for partial seizures in ages 12 and up. It may also be prescribed to treat anxiety disorders and neuropathic pain (including fibromyalgia). For anxiety and neuropathic pain, tiagabine is used primarily to augment other treatments. Tiagabine may be used alongside SSRIs, SNRIs or benzodiazepines for anxiety, or antidepressants, gabapentin, anticonvulsants or opiates for neuropathic pain.

Pharmacology

It is believed that the pharmacology is related to its ability, documented in in vitro experiments, to enhance the activity of gamma aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. These experiments have shown that 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. Evidence is available that it operates as a selective GABA reuptake inhibitor.

Side effects

Tiagabine's most common side effects include confusion, difficulty speaking clearly/stuttering, mild sedation, and in doses over 8 mg, a tingling sensation (paresthesia) in the body's extremities, particularly the hands and fingers. Tiagabine may induce seizures in those without epilepsy, especially if they are taking another drug which lowers the seizure threshold.

With overdoses in the range of 20-40 mg or more it will cause extreme sedation, temporary retardation, muscle tremors and spasms, uncontrollable bodily tremors, retrograde and anterograde amnesia, thrashing, screaming, flailing and extreme hostility, unconsciousness with seizures or seizure-like symptoms. Upon consciousness: extreme confusion with an inability to form coherent sentences, express ideas, or do the most basic activities for several hours. Unlike the benzodiazepines Tiagabine (Gabitril) has been shown to have no recreation value and any euphoria is most likely a placebo effect or because of consumption with alcohol.

Synthesis

Andersen, Knud Erik; Braestrup, Claus; Groenwald, Frederik C.; Joergensen, Anker S.; Nielsen, Erik B.; Sonnewald, Ursula; Soerensen, Per O.; Suzdak, Peter D.; Knutsen, Lars J. S. (1993). "The synthesis of novel GABA uptake inhibitors. 1. Elucidation of the structure-activity studies leading to the choice of (R)-1--3-piperidinecarboxylic acid (Tiagabine) as an anticonvulsant drug candidate". Journal of Medicinal Chemistry. 36 (12): 1716. doi:10.1021/jm00064a005. PMID 8510100.

References

1. ^ Stahl, S. Stahl's Essential Psychopharmacology: Prescriber's Guide. Cambridge University Press: New York, NY. 2009. pp. 523-526
2. Pollack MH, Roy-Byrne PP, Van Ameringen M; et al. (2005). "The selective GABA reuptake inhibitor tiagabine for the treatment of generalized anxiety disorder: results of a placebo-controlled study". The Journal of clinical psychiatry. 66 (11): 1401–8. doi:10.4088/JCP.v66n1109. PMID 16420077. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

External links

• Gabitril (manufacturer's website)
• Pharmacology

• Ill-formatted IPAc-en transclusions
• Anticonvulsants
• GABA reuptake inhibitors
• Thiophenes
• Piperidines
• Carboxylic acids