Characterization of tiagabine (NO-328), a new potent and selective GABA uptake inhibitor

Nielsen, Erik Tetens; Suzdak, Peter D.; Andersen, Knud Erik; Knutsen, Lars J. S.; Sonnewald, Ursula; Bræstrup, Claus

doi:10.1016/0014-2999(91)90438-v

Cited by 223 publications

(146 citation statements)

References 15 publications

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“…8C). Also, this uptake was unaffected by the selective GAT1 inhibitor tiagabine (3 M) (59). Thus, this substrate selectivity did not match that described for GAT1 and BGT1 because rat GAT1 is highly sensitive to tiagabine and rather insensitive to ␤-alanine (60 -62), and BGT1 is sensitive to betaine and less sensitive to (RS)-nipecotic acid (63).…”

Section: E G I and K)mentioning

confidence: 88%

Deletion of the γ-Aminobutyric Acid Transporter 2 (GAT2 and SLC6A13) Gene in Mice Leads to Changes in Liver and Brain Taurine Contents

Zhou

Holmseth

Guo

et al. 2012

Journal of Biological Chemistry

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Background:The physiological roles of GABA transporter 2 (GAT2) are unknown. Results: Deletion of the GAT2 gene reduced liver taurine levels but increased brain levels. Conclusion: GAT2 is unimportant for inactivation of neurotransmitter GABA. Instead, GAT2 is a major taurine transporter in hepatocytes and an efflux transporter at the blood-brain barrier. Significance: GAT2 knockout mice will be crucial for uncovering the roles of GAT2.

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Section: E G I and K)mentioning

confidence: 88%

Deletion of the γ-Aminobutyric Acid Transporter 2 (GAT2 and SLC6A13) Gene in Mice Leads to Changes in Liver and Brain Taurine Contents

Zhou

Holmseth

Guo

et al. 2012

Journal of Biological Chemistry

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“…Diazepam is an agonist at BDZ sites to enhance Cl À current of GABA A , and is a benzodiazepine with CNS depressant properties (Banfi et al, 1982;Atack, 2005). Tiagabine hydrochloride, a selective GABA-reuptake inhibitor, increases GABA tone via GAT1 blockade (Nielsen et al, 1991;Rekling et al, 1990). Buspirone, a serotonin1A receptor partial agonist, also displays an antagonist effect on D(2)-dopamine and the a2-adrenergic receptors (Gobert et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Reduced Anxiety and Depression-Like Behaviors in Mice Lacking GABA Transporter Subtype 1

Liu

Cai

et al. 2006

Neuropsychopharmacol

117

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g-Aminobutyric acid (GABA) transporter subtype 1 (GAT1), which transports extracellular GABA into presynaptic neurons, plays an important regulatory role in the function of GABAergic systems. However, the contributions of the GAT1 in regulating mental status are not fully understood. In this paper, we observed the behavioral alterations of GAT1 knockout (GAT1 À/À ) mice using several depressionand anxiety-related models (eg, the forced-swimming test and the tail-suspension test for testing depression-related behaviors; the openfield test, the dark-light exploration test, the emergence test, and the elevated plus maze (EPM) test for anxiety-related behaviors). Here we found that GAT1 À/À mice showed a lower level of depression-and anxiety-like behaviors in comparison to wild-type mice. Furthermore, GAT1 À/À mice exhibited measurable insensitivity to selected antidepressants and anxiolytics such as fluoxetine, amitriptyline, buspirone, diazepam, and tiagabine in the tail-suspension test and/or the EPM test. Moreover, the basal level of corticosterone was found to be significantly lower in GAT1 À/À mice. These results showed that the absence of GAT1 affects mental status through enhancing the GABAergic system, as well as modifying the serotonergic system and the hypothalamic-pituitary-adrenal (HPA) activity in mice.

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“…Augmenting GABA function is a common mechanism of several antiepileptic drugs such as benzodiazepines and barbiturates (allosteric modulators), baclofen (GABA receptor agonists), GABA reuptake inhibitor (Tiagabine), and GABA transaminase inhibitor (Vigabatrin) [3]. GABA is actively taken up by neuron and astrocyte carrier proteins (including GAT1, GAT4 and BGT-1) and broken down into succinic acid semialdehyde by glutamic acid decarboxylase or repackaged into a vesicle that is released again at the next synaptic transmission [5].…”

Section: Discussionmentioning

confidence: 99%

Seizures in a pediatric patient with a tiagabine overdose

2006

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Introduction: Tiagabine (TGB) is a novel antiepileptic that decreases GABA uptake. The literature contains one report of an adult with epilepsy who ingested up to 1 gram of TGB and developed status epilepticus. We reported on a pediatric patient who ingested significantly less TGB but still developed tonic-clonic seizures.Case report: A previously healthy, 13 kg, two-year-old girl developed generalized tonic-clonic seizure activity at home approximately 1 hour after ingesting 90 mg of her grandmother's TGB (forty five 2 mg tablets). At the hospital she had two 5 minute seizures at 1.5 and 3.5 hours post ingestion. Her serum TGB levels were 530 and 130 ng/ml approximately 5 and 11 hours post-ingestion (5-70 ng/ml trough levels with most probable range for seizure control). She was discharged 27 hours post ingestion, and she was in good condition.Conclusion: An overdose of TGB, a novel anti-epileptic, can cause convulsive seizures.

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Characterization of tiagabine (NO-328), a new potent and selective GABA uptake inhibitor

Cited by 223 publications

References 15 publications

Deletion of the γ-Aminobutyric Acid Transporter 2 (GAT2 and SLC6A13) Gene in Mice Leads to Changes in Liver and Brain Taurine Contents

Deletion of the γ-Aminobutyric Acid Transporter 2 (GAT2 and SLC6A13) Gene in Mice Leads to Changes in Liver and Brain Taurine Contents

Reduced Anxiety and Depression-Like Behaviors in Mice Lacking GABA Transporter Subtype 1

Seizures in a pediatric patient with a tiagabine overdose

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