Pharmacology of vigabatrin.

 (GABA) in the brain by inhibiting the major GABA metabolizing enzyme, GABA transaminase.

Vigabatrin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in epilepsy and disorders of motor control.

 was specifically designed to enhance gamma-aminobutyric acid (

Experimental studies and controlled clinical testing of valproate and vigabatrin

Currently, 2 antiepileptic drugs, valproate (VPA) and

, gamma‐vinyl GABA (GVG), are available, which are supposed to inhibit the degradation of 

The cardiovascular and subjective effects of methamphetamine combined with γ-vinyl-γ-aminobutyric acid (GVG) in non-treatment seeking methamphetamine-dependent volunteers

 (GABA) levels by irreversibly inhibiting GABA transaminase.

Changes in plasma GABA concentration during vigabatrin treatment of epilepsy: a prospective study

Responders had a significant (p < …) increase in mean plasma

 both after short-term (from 0.380 to 0.530 nmol/ml; mean increase: 48%) … after long-term (from 0.392 to 0.618 nmol/ml; mean increase: 71%) 

 treatment, whilst nonresponders had no … changes in GABA levels.

The effect of vigabatrin (gamma-vinyl GABA) on cerebral blood flow and metabolism.

 patient group (1.48+/-1.06 versus 4.03+/-4.19 nm/mL).

Vigabatrin increases human brain homocarnosine and improves seizure control

Effects of vigabatrin on motor potentials evoked with magnetic stimulation.

 concentrations in the central nervous system, duration of silent period studied at various stimulus intensities is not modified after vigabatrin administration.

The effects of clonazepam and vigabatrin in hyperekplexia

 by inhibition of the GABA catabolic enzyme GABA-transaminase.

Human Brain γ‐Aminobutyric Acid Levels and Seizure Control Following Initiation of Vigabatrin Therapy

 content increased following the start of 

 treatment up to a daily dose of 60 mg/kg.

 treatment improved seizure control twofold when 

A comparison of population and standard two‐stage pharmacokinetic analyses of vigabatrin data

, is being developed as an add‐on therapy for uncontrolled complex partial seizure.

Vigabatrin and lamotrigine in refractory epilepsy.

 (VIG) decreases the breakdown of the inhibitory neurotransmitter 

, whereas lamotrigine (LTG) reduces presynaptic excitatory amino acid release.

Vigabatrin: Clinical Evidence Supporting Rational Polytherapy in Management of Uncontrolled Seizures

 is an enzyme‐activated irreversible inhibitor of 

γ‐aminobutyric acid (GABA)‐transaminase

 that increases brain and cerebrospinal (CSF) GABA concentrations in animals and humans.

Effect of gamma aminobutyric acid on the carbon dioxide rebreathing response of normal subjects: a study using vigabatrin.

, a new drug for the treatment of epilepsy, is thought to exert its effect by increasing 

Vigabatrin: rational treatment for chronic epilepsy.

 is a selective, irreversible suicide inhibitor of 

 transaminase and thus increases brain and CSF GABA.

Effect of gamma-vinyl GABA treatment on cholinergic and aminergic neurotransmission and on cyclic nucleotides in human complex partial epilepsy — a CSF study

 (GVG) is a new anticonvulsant drug that enhances levels of 

 in the brain by irreversibly inhibiting GABA transaminase.

Brain gamma-aminobutyric acid abnormality in tardive dyskinesia. Reduction in cerebrospinal fluid GABA levels and therapeutic response to GABA agonist treatment.

A significant decrease in dyskinetic symptoms occurred with the administration of

, associated with a twofold increase in cerebrospinal fluid levels of 

; THIP produced a more moderate, yet consistent decrease in the involuntary movements.

Effects of gamma-vinyl-GABA on the human electroencephalogram

 (GVG) is a new anticonvulsant drug that significantly raises the level of the 

Clinical evaluation of gamma-vinyl-gamma-aminobutyric acid for control of epilepsy in dogs.

 is a novel antiepileptic drug that exerts its effects by increasing the concentration of 

Vigabatrin Inhibits Seizures and mTOR Pathway Activation in a Mouse Model of Tuberous Sclerosis Complex

 levels and inhibited seizures in the mouse model of TSC.

 (GABA) levels, the precise mechanism of action of vigabatrin in TSC is not known.

Agents in Development for the Management of Cocaine Abuse

 indirectly reduce dopamine activity by increasing activity of neurotransmitters (serotonin and 

Enhanced GABAergic tone in the ventral pallidum: memory of unpleasant experiences?

In another set of experiments, intra-VP injections of

 (a GABA transaminase inhibitor) increased extracellular 

 and immobility behaviors in the FST while the direct GABAA receptor antagonist bicuculline reduced immobility behaviors.

Expanding treatment options for cocaine dependence.

 levels, and these increases in GABA-ergic transmission have an inhibitory effect on dopaminergic transmission and centrally mediated reward systems.

 transaminase, the primary enzyme involved in GABA metabolism.

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 

Role of the GABA transporter in epilepsy.

 is enhanced by the anticonvulsants gabapentin and 

GABA transporters and GABA-transaminase as drug targets.

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

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

 and tiagabine exert their pharmacological effects by reducing the inactivation of 

 by inhibiting the enzyme GABA-transaminase, whereas tiagabine blocks the uptake of GABA from the synaptic cleft by an action on the GAT-1 transporter.

Gabapentin and vigabatrin increase GABA in the human neocortical slice

 concentrations in both human and rat neocortical slices by 62% (P<0.001) and 88% (P<0.03), respectively.

The New Generation of GABA Enhancers

 levels by inhibiting the enzyme GABA transaminase which is responsible for intracellular GABA catabolism.

Is there a mechanistic basis for rational polypharmacy?

 at postsynaptic receptors may underlie the clinical efficacy of 

 transaminase, the enzyme that degrades GABA, thereby producing greater available pools of presynaptic GABA for release in central synapses.

[Anticonvulsive drug therapy. Historical and current aspects].

 amount, whereas felbamate and remacemide interact with the NMDA-receptor complex.

Antiepileptic Drug Mechanisms of Action

Antiepileptic Drugs in Development: Prospects for the Near Future

 transaminase which elevates GABA levels in the CNS.

New Antiepileptic Drugs: From Serendipity to Rational Discovery

Work in this field led to the development of

, which inhibits the enzyme responsible for the degradation of 

Neuropathologic Findings in Patients Receiving Long-Term Vigabatrin Therapy for Chronic Intractable Epilepsy

 is a new antiepileptic drug that acts by the irreversible inhibition of 

Pharmacology and Clinical Pharmacology of Vigabatrin

 is an enzyme-activated, irreversible inhibitor of 

 (GABA) aminotransferase, which causes a marked increase in cerebral GABA concentration and a resulting anticonvulsant action.

Navigating the genetic landscape of childhood epilepsy: a new perspective?

 transaminase amongst other actions, can worsen seizures in both myoclonic astatic epilepsy and Angelman syndrome.

Eye Findings on Vigabatrin and Taurine Treatment in Two Patients with Succinic Semialdehyde Dehydrogenase Deficiency.

The mechanism of injury to the retina may be induced by elevations of

 causing peripheral photoreceptor and ganglion cell damage, and this can be exacerbated by the use of 

Vigabatrin efficacy in GPR56‐associated polymicrogyria: The role of GABAA receptor pathway

 in synaptic space (inhibition of the GABA catabolism), and might be effective through the direct activation of the orthosteric site.

Population dose‐response analysis of daily seizure count following vigabatrin therapy in adult and pediatric patients with refractory complex partial seizures

 is an irreversible inhibitor of γ‐aminobutyric acid transaminase (

) and is used as an adjunctive therapy for adult patients with refractory complex partial seizures (rCPS).

Analysis of cerebrospinal fluid γ‐aminobutyric acid by capillary electrophoresis with laser‐induced fluorescence detection

 were obtained in patients taking valproic acid or 

, which are antiepileptic drugs that modulate GABA metabolism.

Mechanisms of GABA release from human astrocytes

 levels were enhanced by treatment with the GABA‐T inhibitors gabaculine or 

A European perspective—Comments on “Infantile spasms: A U.S. consensus report”

 that increase synaptic concentrations of 

 (GABA) in the brain can also cause apoptotic degeneration in the developing animal brain (Bittigau et al., 2003).

Subcortical structures and infantile spasms

Therapeutic agents that can control … as adrenocorticotropic hormone,

 neurotransmission.5 Desguerre et al. hypothesize that ‘subtle’ neuronal cell death, in the basal ganglia, not visible by … but possibly revealed by DWI, might have occurred in their patients as a consequence of sustained epileptic activity.

Current role of vigabatrin in infantile spasms.

), a selective irreversible inhibitor of 

, has proved to be effective against cryptogenic and symptomatic infantile spasms (IS).

Vigabatrin transport across the human intestinal epithelial (Caco‐2) brush‐border membrane is via the H+‐coupled amino‐acid transporter hPAT1

 uptake across the apical membrane was inhibited by 

 and the GABA analogues trans‐4‐aminocrotonic acid (TACA) and guvacine, whereas 1‐(aminomethyl)cyclohexaneacetic acid (gabapentin) had no affect.

In hPAT1 and mPAT1‐expressing Xenopus laevis oocytes

, TACA and guvacine, whereas gabapentin failed to inhibit [3H]GABA uptake.

Neuroactive Amino Acids in Focally Epileptic Human Brain: A Review

, a GABA-T inhibitor and effective antiepileptic, significantly increases brain 

Effects of vigabatrin on brain GABA+/Cr signals in focus‐distant and focus‐near brain regions monitored by 1H‐NMR spectroscopy

Sensorineural hearing loss: A reversible effect of vigabatrin

 (GABA) transaminase with resultant increased concentrations of GABA in the brain and retina.1 Visual field concentric constriction secondary to vigabatrin is a … concentration on retina cells.3  There have been no reports of an association between the use of vigabatrin and sensorineural hearing loss.

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

 levels or neurotransmission at least in part by targeting the metabolic pathways of GABA.

Vigabatrin Decreases Cholecystokinin-Tetrapeptide (CCK-4) Induced Panic in Healthy Volunteers

 (GABA) levels by irreversible inhibition of the GABA-catabolizing enzyme GABA-transaminase (GABA-T).

[GABA-ergic system and antiepileptic drugs].

Tiagabine blocks neuronal and glial uptake of GABA whilst

 increases the synaptic concentration of 

Acute Effects of Vigabatrin on Brain GABA and Homocarnosine in Patients with Complex Partial Seizures

 increases human brain γ‐aminobutyric acid (

) and the related metabolites, homocarnosine and 2‐pyrrolidinone.

Analysis of CSF amino acids in young patients with generalised refractory epilepsy during an add-on study with lamotrigine

 levels were 86% higher in those patients also treated with 

 (vigabatrin, GVG) compared with patients treated with other combinations and this was not altered by co-medication with lamotrigine.

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

 (100 microM) and TGB (200 nM) all significantly (p < 0.05) reduced the uptake of 

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

Vigabatrin: A Novel Therapy for Seizure Disorders

 is a selective and irreversible inhibitor of 

Antiepileptic drug treatment: clinical considerations and concerns.

gamma-aminobutyric acid (GABA)-transaminase

 and enhances GABAergic neuronal inhibition.

Measuring human brain GABA in vivo: effects of GABA-transaminase inhibition with vigabatrin.

 enhances the vesicular and nonvesicular release of 

 irreversibly inhibits GABA-transaminase, raising brain and cerebrospinal fluid (CSF) 

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

 by interfering with reuptake and degradation of GABA, respectively.

Newer Anticonvulsant Drugs

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

Vigabatrin aggravates absences and absence status

Vigabatrin is highly effective against partial seizures with or without secondary generalization.1

 increases the inhibitory neurotransmitter 

 in the brain through an irreversible inhibition of GABA-transaminase.1 Thus, it enhances GABAergic transmission mediated by both GABAA and GABAB receptors.

[Antiepileptic drugs: mechanism of action].

[New medical treatment of epilepsy].

 transaminase, increasing the concentration of this neurotransmittor inhibitor in the brain.

Human brain GABA levels rise rapidly after initiation of vigabatrin therapy

 increased by more than 40% within 2 hours of administration of a single 50 mg/kg oral dose of 

 from 0.95 (SEM, 0.07; n = 7) to 1.34 mmol/kg (SEM, 0.13).

Improvement of stiff-man syndrome with vigabatrin

 concentrations by inhibiting its breakdown, we hypothesised that it may diminish muscle spasms and rigidity in patients with SMS.

Initial Observations on Effect of Vigabatrin on In Vivo 1H Spectroscopic Measurements of γ‐Aminobutyric Acid, Glutamate, and Glutamine in Human Brain

 levels were increased in all patients treated with 

Mechanisms of action of antiepileptic drugs

The compounds acting on GABAergic systems may be further subdivided into those which modulate … chloride channels, e.g. the barbiturates and the benzodiazepines; those compounds, in particular

 by blocking GABA transaminase; and those which inhibit … re-uptake of GABA into the presynaptic terminal.

Status epilepticus during vigabatrin treatment: A report of three cases

 (gamma-vinyl-GABA or GVG) is an irreversible inhibitor of 

 (GABA-T), which is an enzyme responsible for gamma-aminobutyric acid (GABA) catabolism.

Vigabatrin: effect on brain GABA levels measured by nuclear magnetic resonance spectroscopy

NMRS studies show that following administration of

 rise to about 2‐3 times their baseline values.

 levels in the presynaptic nerve terminal by inhibiting the activity of GABA‐transaminase.

Determination of GABA and vigabatrin in human plasma by a rapid and simple HPLC method: correlation between clinical response to vigabatrin and increase in plasma GABA

) acts by inhibiting degradation of the inhibitory neurotransmitter 

 (GABA), increasing the GABA concentrations in the brain.

Effect of long-term vigabatrin therapy on GABA and other amino acid concentrations in the central nervous system — a case study

 caused a three-fold increase in total and free 

Neuropathology of a human hippocampus following long-term treatment with vigabatrin: lack of microvacuoles

 (gamma-vinyl-GABA), an irreversible inhibitor of 

, has been reported to be effective in the treatment of refractory epilepsies.

Cerebrospinal fluid GABA and seizure control with vigabatrin.

 dose reduction resulted in a concomitant decrease in 

Clinical pharmacology of vigabatrin.

 produces dose-related increases in CSF concentrations of free and total 

, homocarnosine (the GABA-histidine dipeptide) and beta-alanine.

Clinical and biochemical effects of gamma-vinyl Gaba in tardive dyskinesia.

 and homocarnosine concentrations increased from three to five fold with 

Amelioration of cerebral vasospasm and secondary injury by Vigabatrin following experimental subarachnoid hemorrhage in the rabbit.

, an antiepileptic drug, increases the level of 

 in the brain via inhibiting its catabolism.

Dietary GABA induces endogenous synthesis of a novel imidazole peptide homocarnosine in mouse skeletal muscles

 (inhibitor of GABA transaminase (GABA-T)) administration to mice receiving 2% 

 intake for 2 weeks led to GABA-T inhibition in the liver.

Immediate versus late effects of vigabatrin on spike and wave discharges

 concentrations are known to be increased for several days, the present study sheds light on how the previously described changes in SWD characteristics develop over a longer time frame.

 concentrations by inhibiting GABA transaminase.

supp.ai

Discover Supplement-Drug Interactions

Possible Interaction: Gamma-Aminobutyric Acid and Vigabatrin

Share:

Gamma-Aminobutyric Acid

Vigabatrin

Research Papers that Mention the Interaction