Tiagabine
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| Systematic (IUPAC) name |
| (R)-1-[4,4-bis(3-methylthiophen-2-yl)but-3-enyl] piperidine-3-carboxylic acid |
| Clinical data |
| Trade names |
Gabitril |
| AHFS/Drugs.com |
monograph |
| MedlinePlus |
a698014 |
| Pregnancy cat. |
B3 (Au), C (U.S.) |
| Legal status |
POM (UK), ℞-only (U.S.) |
| Routes |
Oral |
| Pharmacokinetic data |
| Bioavailability |
90% |
| Protein binding |
96% |
| Metabolism |
Hepatic (CYP450 system) |
| Half-life |
7-9 hours |
| Excretion |
Fecal and renal |
| Identifiers |
| CAS number |
115103-54-3  Y |
| ATC code |
N03AG06 |
| PubChem |
CID 60648 |
| DrugBank |
DB00906 |
| ChemSpider |
54661 Y |
| UNII |
Z80I64HMNP Y |
| KEGG |
D08588 Y |
| ChEMBL |
CHEMBL1027 Y |
| Chemical data |
| Formula |
C20H25NO2S2 |
| Mol. mass |
375.55 g/mol |
- O=C(O)[C@H]1CN(CCC1)CC/C=C(/c2sccc2C)c3sccc3C
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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 Y
Key:PBJUNZJWGZTSKL-MRXNPFEDSA-N Y
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 Y (what is this?) (verify)
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Tiagabine (pron.: /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 by a team of chemists and pharmacologists under the general direction of Dr. Claus Bræstrup. An article authored by Dr. Lars J. S. Knutsen describing the design, selection, pharmacology and synthesis of tiagabine was published in the Journal of Medicinal Chemistry in 1993, pulling together the work of the team at Novo Nordisk. The drug and was co-developed with Abbott, in a 40/60 cost sharing deal, with Abbott paying a premium for licensing the IP from the Danish company.
Abbott did initially embrace the drug enthusiastically after its US launch in 1998, and provided further clinical studies with the goal of gaining FDA approval for monotherapy in epilepsy. However, the senior management at Abbott drew back after realizing that the original deal with Novo would limit the company's financial gain from a monotherapy approval. After a period of co-promotion, Cephalon licensed Tiagabine from Abbott/Novo and now is the exclusive producer. The medication is also utilized in the treatment of panic disorder, as are a few other anticonvulsants.
Indications [edit]
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 off-label by physicians knowledgeable about the field 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. [1]
Pharmacology [edit]
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.[2]
Side effects [edit]
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.[1]
Tiagabine overdose can produce neurologic symptoms such as lethargy, seizures (multiple), status epilepticus, seizure (single), coma, confusion, agitation, tremors, dizziness, dystonias/abnormal posturing, and hallucinations. Other symptoms of tiagabine overdose include respiratory depression, tachycardia, hypertension, and hypotension.
Synthesis [edit]
Andersen, Knud Erik; Braestrup, Claus; Groenwald, Frederik C.; Joergensen, Anker S.; Nielsen, Erik B.; Sonnewald, Ursula; Soerensen, Per O.; Suzdak, Peter D. et al. (1993). "The synthesis of novel GABA uptake inhibitors. 1. Elucidation of the structure-activity studies leading to the choice of (R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid (Tiagabine) as an anticonvulsant drug candidate". Journal of Medicinal Chemistry 36 (12): 1716. doi:10.1021/jm00064a005. PMID 8510100.
References [edit]
External links [edit]
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