Tiagabine

Last updated
Tiagabine
Tiagabine.svg
Clinical data
Pronunciation /tˈæɡəbn/
Trade names Gabitril
AHFS/Drugs.com Monograph
MedlinePlus a698014
Pregnancy
category
  • AU:B3
Routes of
administration
Oral (tablets)
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 90–95% [1]
Protein binding 96% [1]
Metabolism Hepatic (CYP450 system, [1] primarily CYP3A) [2]
Onset of action Tmax = 45 min [2]
Elimination half-life 5–8 hours [3]
Excretion Fecal (63%) and renal (25%) [2]
Identifiers
  • (−)-(3R)-1-[4,4-bis(3-methyl-2-thienyl)-3-buten-1-yl]-3-piperidinecarboxylic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C20H25NO2S2
Molar mass 375.55 g·mol−1
3D model (JSmol)
  • O=C(O)[C@H]1CN(CCC1)CC/C=C(/c2sccc2C)c3sccc3C
  • 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 Yes check.svgY
  • Key:PBJUNZJWGZTSKL-MRXNPFEDSA-N Yes check.svgY
   (verify)

Tiagabine (trade name Gabitril) is an anticonvulsant medication produced by Cephalon that is used in the treatment of epilepsy. The drug is also used off-label in the treatment of anxiety disorders and panic disorder.

Contents

Medical uses

Tiagabine is approved by U.S. Food and Drug Administration (FDA) as an adjunctive treatment for partial seizures in individuals of age 12 and up. It may also be prescribed off-label by physicians to treat anxiety disorders and panic disorder as well as neuropathic pain (including fibromyalgia). For anxiety and neuropathic pain, tiagabine is used primarily to augment other treatments. Tiagabine may be used alongside selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, or benzodiazepines for anxiety, or antidepressants, gabapentin, other anticonvulsants, or opioids for neuropathic pain. [4] It is effective as monotherapy and combination therapy with other antiepileptic drugs in the treatment of partial seizure. [5]

Side effects

Side effects of tiagabine are dose related. [5] The most common side effect of tiagabine is dizziness. [6] Other side effects that have been observed with a rate of statistical significance relative to placebo include asthenia, somnolence, nervousness, memory impairment, tremor, headache, diarrhea, and depression. [6] [7] Adverse effects such as confusion, aphasia (difficulty speaking clearly)/stuttering, and paresthesia (a tingling sensation in the body's extremities, particularly the hands and fingers) may occur at higher dosages of the drug (e.g., over 8 mg/day). [6] Tiagabine may induce seizures in those without epilepsy, particularly if they are taking another drug which lowers the seizure threshold. [4] There may be an increased risk of psychosis with tiagabine treatment, although data is mixed and inconclusive. [1] [8] Tiagabine can also reportedly interfere with visual color perception. [1]

Warning

Overdose

Tiagabine overdose can produce neurological symptoms such as lethargy, single or multiple seizures, status epilepticus, coma, confusion, agitation, tremors, dizziness, dystonias/abnormal posturing, and hallucinations, as well as respiratory depression, tachycardia, hypertension, and hypotension. [10] Overdose may be fatal especially if the victim presents with severe respiratory depression and/or unresponsiveness. [10]

Pharmacology

Tiagabine increases the level of γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system, by blocking the GABA transporter 1 (GAT-1), and hence is classified as a GABA reuptake inhibitor (GRI). [3] [11]

Pharmacodynamics

Tiagabine is primarily used as an anticonvulsant in the treatment of epilepsy as a supplement. Although the exact mechanism by which Tiagabine exerts its antiseizure effect is unknown, it is thought to be related to its ability to increase the activity of gamma aminobutyric acid (GABA), the central nervous system's major inhibitory neurotransmitter. Tiagabine attaches to the GABA uptake carrier's recognition sites. Tiagabine is thought to block GABA uptake into presynaptic neurons as a result of this action, allowing more GABA to be available for receptor binding on the surfaces of post-synaptic cells. [12]

Monitoring Parameters

Seizure frequency, liver function tests , suicidality [13]

History

Tiagabine was discovered at Novo Nordisk in Denmark in 1988 by a team of medicinal chemists and pharmacologists under the general direction of Claus Bræstrup. [14] 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 ]

U.S. patents on tiagabine listed in the Orange Book expired in April 2016. [15]

See also

Related Research Articles

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Levetiracetam Medication

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Clonazepam Benzodiazepine sedative

Clonazepam, sold under the brand Klonopin among others, is a medication used to prevent and treat seizures, panic disorder, anxiety, and the movement disorder known as akathisia. It is a tranquilizer of the benzodiazepine class. It is taken by mouth. Effects begin within one hour and last between six and twelve hours.

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Zonisamide

Zonisamide, sold under the brand name Zonegran, is a medication used to treat the symptoms of epilepsy and Parkinson's disease. Chemically it is a sulfonamide. It serves as an anticonvulsant used primarily as an adjunctive therapy in adults with Parkinson's disease, partial-onset seizures; infantile spasm, mixed seizure types of Lennox–Gastaut syndrome, myoclonic and generalized tonic clonic seizure. Despite this it is also sometimes used as a monotherapy for partial-onset seizures.

Stiripentol

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Sultiame

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Seletracetam

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Lacosamide Anticonvulsant and analgesic medication

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Tetrahydrodeoxycorticosterone

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GABA reuptake inhibitor

A GABA reuptake inhibitor (GRI) is a type of drug which acts as a reuptake inhibitor for the neurotransmitter gamma-Aminobutyric acid (GABA) by blocking the action of the gamma-Aminobutyric acid transporters (GATs). This in turn leads to increased extracellular concentrations of GABA and therefore an increase in GABAergic neurotransmission.

CI-966

CI-966 (developmental code name) is a central nervous system depressant acting as a GABA reuptake inhibitor, specifically a highly potent and selective blocker of the GABA transporter 1 (GAT-1) (IC50 = 0.26 μM), and hence indirect and non-selective GABA receptor full agonist. It was investigated as a potential anticonvulsant, anxiolytic, and neuroprotective therapeutic but was discontinued during clinical development due to the incidence of severe adverse effects at higher doses and hence was never marketed.

References

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