Tiagabine for the treatment of generalized anxiety disorder: a randomized, open-label, clinical trial with paroxetine as a positive control.

, a selective GABA reuptake inhibitor, enhances normal 

Tiagabine: Absence of Kinetic or Dynamic Interactions with Ethanol

 is a new antiepileptic drug that inhibits the uptake of 

[Tiagabine: a GABA-ergic anti-epileptic drug].

) is a new anti-epileptic drug which inhibits the uptake of 

 by the neurons and glia and prolongs the time GABA remains at the synapse.

Long-term cognitive and EEG effects of tiagabine in drug-resistant partial epilepsy

Adjunctive treatment of partial seizures with tiagabine: A placebo-controlled trial

 is a new antiepileptic drug which acts by a novel mechanism, inhibiting the reuptake of the inhibitory neurotransmitter 

Pharmacological Characterization of a Betaine/GABA Transporter 1 (BGT1) Inhibitor Displaying an Unusual Biphasic Inhibition Profile and Anti-seizure Effects

Focal epileptic seizures can in some patients be managed by inhibiting

 (GABA) uptake via the GABA transporter 1 (GAT1) using 

The Subcellular Localization of GABA Transporters and Its Implication for Seizure Management

 levels has been demonstrated by using the clinically effective and selective GAT1 inhibitor 

 [(R)-N-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]nipecotic acid].

The simultaneous inhibition of synaptic and extrasynaptic

 and EF1502, respectively has been demonstrated to exert a synergistic anticonvulsant effect in several seizure models in mice.

Glial modulation of GABAergic and glutamat ergic neurotransmission.

Inhibition of either degradation or clearance of

 has been successfully applied in the development of antiepileptics such as vigabatrin or 

GABA transporters and GABA-transaminase as drug targets.

 and Vigabatrin, two anti-epileptic drugs on the market today, specifically inhibit 

Pre-clinical studies with the GABAergic compounds vigabatrin and tiagabine.

 exert their pharmacological effects by reducing the inactivation of 

Bi‐directional transport of GABA in human embryonic kidney (HEK‐293) cells stably expressing the rat GABA transporter GAT‐1

), as well as, substrates of the rGAT‐1 (e.g. GABA, nipecotic acid) concentration dependently decreased 

 uptake and increased efflux of [3H]‐GABA from pre‐labelled cells.

Cellular mechanisms of pharmacoresistance in slices from epilepsy surgery.

 markedly prolonged the effects of released 

 at GABAA receptors, but paired-pulse behaviour was only slightly affected.

The New Generation of GABA Enhancers

 levels by inhibiting the GABA uptake transporter, GAT1, and preventing the uptake of GABA into neurons and glia.

A Review of the Preclinical Pharmacology of Tiagabine: A Potent and Selective Anticonvulsant GABA Uptake Inhibitor

Together these biochemical data suggest that the in vitro and in vivo mechanism of action of

 uptake specifically, resulting in an increase in GABAergic mediated inhibition in the brain.

Tiagabine Pharmacology in Profile

 administration prolongs neuronal depolarization induced by iontophoretically applied 

 has been shown to increase extracellular overflow of 

Review of toxicity and trends in the use of tiagabine as reported to US poison centers from 2000 to 2012

 is a novel antiepileptic that acts by increasing synaptic and extracellular 

Imaging the "GABA shift" in schizophrenia.

Differences between antipsychotic-free and antipsychotic-naive patients here may be a sampling artifact and not necessarily related … se, especially in the absence of a clear relationship between The authors conclude that low levels of

 in antipsychoticnaive patients and to … a potential compensatory mechanism.

 in antipsychotic-naive patients and to up-regulation of receptors as a potential compensatorymechanism.

Measurement of GABA using J‐difference edited 1H‐MRS following modulation of synaptic GABA concentration with tiagabine

 and neurotransmission through studies using other imaging modalities, and significant increases in self‐reported sleepiness scales were observed.

Enhancement of slow wave sleep: implications for insomnia.

 is an inhibitor of GAT-1, one of four transporter proteins that promote the reuptake of 

 (GABA) into presynaptic terminals and surrounding glial cells.

Tiagabine: Let seizing dogs lie?

 is a nipecotic acid analogue that increases extracellular concentrations of 

 (GABA) by inhibiting its reuptake into neuronal and glial cells at the synaptic cleft.

Topiramate in Traumatic Brain Injury: Adverse Effects on Cognitive Function

Yet, not all AEDs are equally impairing to cognition, and it likely involves more than the potentiation of …, since gabapentin is thought to act on the GABA system but has relatively few cognitive effects2; similarly,

, has fewer cognitive side … topiramate.3 The mul-

Age-correlated decline in [3H]tiagabine binding to GAT-1 in human frontal cortex

 is a ligand for GABAergic neurons, which binds with 10-fold higher affinity to the 

Retrospective Evaluation of Tiagabine Overdose

 is an anticonvulsant that blocks reuptake of the inhibitory neurotransmitter 

Tiagabine Overdose: A Case of Status Epilepticus in a Non-Epileptic Patient

 is an antiepileptic drug used as adjunctive therapy for partial seizures that is believed to selectively inhibit the presynaptic reuptake of 

Treatment of painful sensory neuropathy with tiagabine: A pilot study

 and might enhance the central pain-control mechanisms.

Effects of tiagabine on cholecystokinin‐tetrapeptide (CCK‐4)‐induced anxiety in healthy volunteers

 is an antiepileptic drug, which increases 

 via selective blockade of GABA reuptake.

The role of GABA in the pathophysiology and treatment of anxiety disorders.

 availability by blocking the reuptake of GABA via transporter inhibition.

Effects of antiepileptic drugs on visual function, with special reference to Vigabatrin.

VGB is a selective irreversible inhibitor of GABA-transaminase and

 blocks the neuronal and glial reuptake of 

Ethical dilemmas of potential adverse events.

), also a gabaergic AEM recently approved for sale, has not been reported to cause field defects but raising 

[
 3
 H
 ]Tiagabine binding to GABA uptake sites in human brain

Inhibition experiments with gamma-aminobutyric acid (GABA), GABA uptake inhibitors, ligands active at postsynaptic GABA receptors and receptors for other neurotransmitters, suggest that

[Clinical implications of pharmacology and pharmacokinetics of tiagabine].

 is a new antiepileptic drug which acts by blocking neuronal and glial 

 uptake and it is indicated in the treatment of partial epilepsies.

Effects of valproate, vigabatrin and tiagabine on GABA uptake into human astrocytes cultured from foetal and adult brain tissue.

 (200 nM) all significantly (p < 0.05) reduced the uptake of 

 into primary cultures of human adult astrocytes following a one hour exposure.

Tiagabine: a new therapeutic option for people with intellectual disability and partial epilepsy.

 exerts its antiepileptic drug (AED) activity by selectively inhibiting the uptake of 

 (GABA) onto the transporter molecules, and thus, increasing extracellular concentrations of GABA in the brain.

Antiepileptic Drug Cellular Mechanisms of Action: Where Does Lamotrigine Fit In?

 and vigabatrin enhance cerebrospinal levels of 

 by interfering with reuptake and degradation of GABA, respectively.

Newer Anticonvulsant Drugs

 and vigabatrin is very specific; both agents increase 

 (GABA) levels through inhibition of reuptake and catabolism respectively.

Tiagabine approved for partial seizures.

 binds to recognition sites associated with the 

Deliberate overdose with the novel anticonvulsant tiagabine

 is a novel antiepileptic drug which acts by decreasing 

Effects of γ‐Aminobutyric acid transporter 1 inhibition by tiagabine on brain glutamate and γ‐Aminobutyric acid metabolism in the anesthetized rat In vivo

The results suggest that any reduction in

 might be an indirect response to reduced glutamatergic drive rather than direct compensatory effects.

Synthesis and pharmacological properties of new GABA uptake inhibitors.

 uptake are used as antiepileptic drugs (

 - a selective GAT1 inhibitor), they are also being investigated for other indications, including treatment of psychosis, general anxiety, sleep disorders, drug addiction or acute and chronic pain.

Metabolism of [1,6-13C]Glucose and [U-13C]Glutamine and Depolarization Induced GABA Release in Superfused Mouse Cerebral Cortical Mini-slices

 release could be reduced (50%) by the GABA transport inhibitor 

 (25 μM) or by replacing Ca2+ with Co2+.

Reversal of GABA-mediated inhibition of the electrically and potassium chloride evoked [3H]-GABA release from rat substantia nigra slices by DL-3-hydroxy-3-phenyl pentanamide.

The addition of DL-HEPP (100 micromol/L) alone did not affect the … control, but it was able to significantly reduce the inhibitory effect of

 (CAS 56-12-2) (10 micromol/L) on [3H]-… and potassium chloride stimulation, in the presence of 

High-affinity GABA uptake and GABA-metabolizing enzymes in pig forebrain white matter: A quantitative study

 (0.1 microM), an antiepileptic drug that specifically inhibits the GAT-1 GABA transporter inhibited 

 uptake 50% in temporal cortex and 60-68% in white structures.

Altered cortico‐striatal synaptic plasticity and related behavioural impairments in reeler mice

) re‐uptake system, the probability that (rl/rl) mice showed LTP decreased significantly, thus suggesting an impaired GABAergic transmission in reeler mutants.

Effect of combined administration of ethanol and tiagabine on rabbit EEG.

 is a new generation antiepileptic drug, a specific inhibitor of 

 (GABA) reuptake from the synaptic space to neurons and glia.

Behavioural correlates of an altered balance between synaptic and extrasynaptic GABAAergic inhibition in a mouse model

, an antiepileptic GABA‐uptake … that increases brain 

 levels, delayed picrotoxinin‐induced convulsions at a low dose of 3.2 mg/kg in Thy1α6 mice, but not in control mice; however, the overall effect of higher tiagabine doses on the convulsion latency remained smaller in the Thy1α6 mice.

Effects of the GABA-uptake inhibitor tiagabine in rat globus pallidus

This finding could be explained by the proposition that in the presence of

 on GABA receptors would dominate over the inhibitory effect of tiagabine on GABA release.

Glutamate modulation of GABA transport in retinal horizontal cells of the skate

 (1 mm) elicited an inward current that was completely suppressed by the GABA transport inhibitors 

 (10 μm) and SKF89976‐A (100 μm), but was unaffected by 100 μm picrotoxin.

Correlation between Anticonvulsant Activity and Inhibitory Action on Glial γ-Aminobutyric Acid Uptake of the Highly Selective Mouse γ-Aminobutyric Acid Transporter 1 Inhibitor 3-Hydroxy-4-amino-4,5,6,7-tetrahydro-1,2-benzisoxazole and ItsN-Alkylated Analogs

 was approximately 1000-fold more potent thanexo-THPO … its alkyl derivatives as an inhibitor of 

 uptake in cultured neural cells and GAT1-expressing HEK 293 cells.exo-THPO, its alkylated analogs, and tiagabine displayed a time- and dose-dependent inhibition of audiogenic seizures after i.c.v.

Pre‐ Rather than Co‐application of Vigabatrin Increases the Efficacy of Tiagabine in Hippocampal Slices

 uptake is the main mechanism of action of 

Efficacy of background GABA uptake in rat hippocampal slices

Whole-cell patch clamp recordings of CA1 pyramidal cells revealed small increases in chloride conductance at 5–10 μM GABA which increased dramatically upon addition of the

GABA-level increasing and anticonvulsant effects of three different GABA uptake inhibitors

 (a selective inhibitor of GABA transporter 1, GAT-1), SNAP-5114 (a semi-selective inhibitor of rat GAT-3/mouse GAT4) and NNC 05-2045 (a non-selective GABA uptake inhibitor) in modulating 

 (30 microM, perfused through the microdialysis probe in halothane anaesthetized rats) increased 

 levels to (% basal+/-SEM) 645+/-69 in the hippocampus and 409+/-61 in the thalamus.

Activity-dependent enhancement of hyperpolarizing and depolarizing γ-aminobutyric acid (GABA) synaptic responses following inhibition of GABA uptake by tiagabine

Thus, measurements of the time integral of evoked responses showed that with weak (60 microA) HFS, tiagabine caused a 3.6-fold increase in the area of hyperpolarization while, in contrast, with strong (530 microA) HFS,

 produced a 13.5-fold increase in the depolarizing actions of 

Inhibition of uptake, steady‐state currents, and transient charge movements generated by the neuronal GABA transporter by various anticonvulsant drugs

, a well‐known inhibitor of GAT1‐mediated transport, but also the other drugs efficiently inhibit the uptake of 

Inhibitory nature of tiagabine-augmented GABAA receptor-mediated depolarizing responses in hippocampal pyramidal cells.

 has recently been reported to facilitate the depolarizing actions of 

 in the CNS of adult rats following the stimulation of inhibitory pathways at a frequency (100 Hz) intended to mimic interneuronal activation during epileptiform activity.

Neurochemical actions of vigabatrin and tiagabine alone and in combination in mouse cortex.

 levels when neither drug had such an effect alone.

Analysis of the kinetics of synaptic inhibition points to a reduction in GABA release in area CA1 of the genetically epileptic mouse, El


Reduction of GABA release (by reducing [Ca2+]… or paired-pulse stimulation) or blockade of

) led to the conclusion that small changes in the amount of GABA available for postsynaptic binding … little effect on the peak amplitude, but have marked effect on the duration of the IPSC.

Effects of tiagabine and vigabatrin on GABA uptake into primary cultures of rat cortical astrocytes

 (200 nM) and VGB (100 microM) treatments reduced 

 uptake when compared to both control and VGB treated cultures.

 uptake was also reduced following eight and 24 hour exposures to 200 nM 

 (100-300 nM) and VGB (100 microM) reduced 

 uptake when compared to control at four hours post-exposure.

Effects of chronic tiagabine treatment on [3H]GABAA, [3H]GABAB and [3H]tiagabine binding to sections from mice brain

(R)-N-(4,4-Bis(3-methyl-2-thienyl)but-3-en-1-yl)nipecotic acid

 (GABA) uptake, which maintains its initial anticonvulsant effects when administered to mice for a prolonged period (21 days).

Effects of the GABA-uptake inhibitor tiagabine on electroencephalogram, spike-wave discharges and behaviour of rats

, since it acts as a GABA re-uptake inhibitor.

Postischemic inhibition of GABA reuptake by tiagabine slows neuronal death in the gerbil hippocampus

 significantly reduced the ischemic‐induced elevation of glutamate levels in area CA1 during the postischemic period when 

Blockade of GABA Uptake with Tiagabine Inhibits Audiogenic Seizures and Reduces Neuronal Firing in the Inferior Colliculus of the Genetically Epilepsy-Prone Rat

 may act to inhibit audiogenic seizures, in part, by intensifying these naturally occurring forms of acoustically evoked inhibition in inferior colliculus neurons.

These data are consistent with enhancement by

 (GABA)-mediated inhibition in IC, which is most prominent at high acoustic intensities.

 is a new anticonvulsant drug that blocks the uptake of 

, prolonging the action of this inhibitory transmitter.

Factors contributing to the decay of the stimulus-evoked IPSC in rat hippocampal CA1 neurons.

 (20-50 microM), increased t1/2 of a single IPSC by 114% without affecting Ipeak.

Rat substantia nigra pars reticulata neurones are tonically inhibited via GABA A, but not GABA B, receptors in vitro

 uptake, caused an inhibition of firing which could be reversed with bicuculline (30 microM) but not CGP 55845A (1 microM).

The gamma-aminobutyric acid (GABA) uptake inhibitor, tiagabine, increases extracellular brain levels of GABA in awake rats.

 increased the extracellular concentrations of 

 in globus pallidus with peak values 310% of basal level (after 21 mg/kg) and 240% of basal level (after 11.5 mg/kg).

Tiagabine induced modulation of oscillatory connectivity and activity match PET-derived, canonical GABA-A receptor distributions

This study explored the effects of pharmacologically blocking the reuptake of

 (increasing local concentrations) using the GABA transporter 1 (GAT1) blocker, 

Tiagabine

Tiagabine treatment in kainic acid induced cerebellar lesion of dystonia rat model

 is a selective GABA transporter inhibitor, which blocks the reuptake and recycling of 

New developments in the treatment of partial-onset epilepsy

 both increase GABA activity, by inhibiting 

 transaminase and limiting GABA reuptake, respectively.

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Possible Interaction: Gamma-Aminobutyric Acid and Tiagabine

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Research Papers that Mention the Interaction