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Tiagabine

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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
  • AU: B3
  • US: C (Risk not ruled out)
Oral
Pharmacokinetic data
Bioavailability 90%
Protein binding 96%
Metabolism Hepatic (CYP450 system)
Half-life 7-9 hours
Excretion Fecal and renal
Identifiers
115103-54-3 7pxY
N03AG06
PubChem CID 60648
DrugBank DB00906 7pxY
ChemSpider 54661 7pxY
UNII Z80I64HMNP 7pxY
KEGG D08588 7pxY
ChEBI CHEBI:9586
ChEMBL CHEMBL1027 7pxY
Chemical data
Formula C20H25NO2S2
375.55 g/mol
 14pxY (what is this?)  (verify)

Tiagabine (/tˈæɡəbn/ is an anti-convulsive medication produced by Cephalon and marketed under the brand name Gabitril. The medication is also utilized in the treatment of panic disorder, as are a few other anticonvulsants.[citation needed]

Discovery

The drug was discovered at Novo Nordisk in Denmark in 1988 by a team of medicinal chemists and pharmacologists under the general direction of Dr. Claus Bræstrup.[1] The drug was co-developed with Abbott Laboratories, in a 40/60 cost sharing deal, with Abbott paying a premium for licensing the IP from the Danish company.[citation needed]

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.[citation needed]

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 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.[2]

Pharmacology

Tiagabine increases the level of gamma aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system by blocking the GABA transporter and hence is classified as a GABA reuptake inhibitor.[3]

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.[2]

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. Overdose may be fatal especially if the victim presents with severe respiratory depression and/or fails to respond to verbal and physical stimuli. Emergency medical services should be sought immediately for any overdose.[citation needed]

Synthesis

File:Tiagabine Rxn.png
Tiagabine synthesis:[1]

Unapproved off-label promotion

The attorneys-general of Connecticut and Pennsylvania have launched investigations into its diversion from the legitimate pharmaceutical market, including Cephalon's "sales and promotional practices for Provigil, Actiq and Gabitril".[citation needed]

See also

References

  1. ^ a b Andersen KE, Braestrup C, Grønwald FC, Jørgensen AS, Nielsen EB, Sonnewald U, Sørensen PO, Suzdak PD, Knutsen LJ (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". J. Med. Chem. 36 (12): 1716–25. PMID 8510100. doi:10.1021/jm00064a005. 
  2. ^ a b Stahl, S. Stahl's Essential Psychopharmacology: Prescriber's Guide. Cambridge University Press: New York, NY. 2009. pp. 523-526
  3. ^ Pollack MH, Roy-Byrne PP, Van Ameringen M, Snyder H, Brown C, Ondrasik J, Rickels K (November 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. PMID 16420077. doi:10.4088/JCP.v66n1109. 

External links