Double‐Blind, Placebo‐Controlled Study of Vigabatrin (Gamma‐Vinyl GABA) in Drug‐Resistant Epilepsy

Loiseau, P; Hardenberg, J.; Pestre, M; Guyot, M.; Schechter, Paul J.; Tell, G.

doi:10.1111/j.1528-1157.1986.tb03512.x

Cited by 130 publications

(73 citation statements)

References 19 publications

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“…Vigabatrin (-y-vinyl GABA), a specific, enzymeactivated irreversible inhibitor of GABA-transaminase (GABA-T) has been shown to be an effective anti-convulsant agent for complex partial seizures (Gram et al, 1983;Browne et al, 1983;Rimmer & Richens, 1984;Gram et al, 1985;Loiseau et al, 1986;Schechter, 1986;Tartara et al, 1986;Tassinari et al, 1987). In all published studies to date vigabatrin has been administered orally on a twice-daily schedule.…”

Section: Introductionmentioning

confidence: 99%

The effect of different vigabatrin treatment regimens on CSF biochemistry and seizure control in epileptic patients.

Ben‐Menachem

Persson

Schechter

et al. 1989

Brit J Clinical Pharma

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1. Vigabatrin, 50 mg kg‐1, was administered orally as add‐on therapy to 11 patients with drug‐resistant complex partial epilepsy as a single dose, then once every third day for 2 months, every other day for 2 months and daily for 1 month. 2. Lumbar punctures were carried out prior to treatment and at the end of each dosage regimen and cerebrospinal fluid (CSF) evaluated for concentrations of free and total GABA, homocarnosine (GABA‐histidine dipeptide), homovanillic acid (HVA), 5‐hydroxyindole acetic acid (5‐HIAA) and vigabatrin. 3. Each regimen resulted in significant increases in CSF concentrations of free and total GABA and homocarnosine compared with the immediately preceding regimen. 4. CSF concentrations of HVA significantly increased after a single vigabatrin dose but returned to pre‐treatment levels with subsequent dosing schedules. In contrast, 5‐HIAA concentrations also increased with the single dose but were significantly decreased, compared with pre‐treatment values, following alternate day and daily vigabatrin administration. 5. Seizure frequency progressively decreased with decreasing dosing interval. Daily vigabatrin administration was associated with greater than 50% decrease in seizures in 8 of the 10 patients treated.

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Section: Introductionmentioning

confidence: 99%

The effect of different vigabatrin treatment regimens on CSF biochemistry and seizure control in epileptic patients.

Ben‐Menachem

Persson

Schechter

et al. 1989

Brit J Clinical Pharma

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“…Vigabatrin (-y-vinyl GABA) is a new antiepileptic drug, recently demonstrated to have a consistent anticonvulsant effect in double-blind placebo-controlled trials of patients with chronic drug-resistant epilepsy (Rimmer & Richens, 1984;Gram et al, 1985, Loiseau et al, 1986Tartara et al, 1986). The postulated mechanism of action of vigabatrin in epilepsy is believed to be irreversible or 'suicide' inhibition of the cerebral enzyme, GABA-aminotransferase (GABA-T), resulting in elevated brain concentrations of the inhibitory neurotransmitter, -yaminobutyric acid (GABA) .…”

Section: Introductionmentioning

confidence: 99%

Inhibition of the enzyme, GABA‐aminotransferase in human platelets by vigabatrin, a potential antiepileptic drug.

Rimmer¹,

Kongola²,

Richens³

1988

Brit J Clinical Pharma

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1. The effect of the new antiepileptic drug, vigabatrin (gamma‐vinyl GABA), on the platelet enzyme, GABA‐aminotransferase (GABA‐T) was investigated in volunteers and patients. Platelets GABA‐T activity was assayed using a radioenzymic method. 2. Three single oral doses of vigabatrin (1 g, 2 g and 4 g) were given to six healthy male volunteers in an open randomised cross over study and compared with a baseline period preceding the three treatments. 3. Significant inhibition of the platelet GABA‐T was produced by treatment with all three doses and a dose‐response relationship was demonstrated. The minimum enzyme activities after 1 g, 2 g and 4 g doses were 43%, 30% and 21% respectively compared with the control values. 4. A significant depression of enzyme activity occurred at 30 min after drug administration and the values remained below control values for 72 h post‐dose, outlasting the presence of the drug itself in the plasma. 5. Eight patients with chronic refractory epilepsy were treated with vigabatrin for 6 weeks. After taking the 2 g daily dose for 1 week there was a marked reduction in platelet enzyme activity in all subjects but the enzyme inhibition produced by the 3 g dose was not significantly different from that produced by the 2 g dose, even after 4 weeks treatment with the larger dose. The mean enzyme activity was approximately 30% throughout the active treatment period. One week after stopping vigabatrin, the enzyme levels were not significantly different from the baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…This was demonstrated in an adjunctive crossover study in which seizures worsened in some patients crossing over from VGB to placebo but not in those changing from placebo to VGB (20)(21)(22). A withdrawal rate of 0.5-1 @week is usually safe.…”

Section: Effect Of Age and Disease Statementioning

confidence: 99%

“…In most studies, responder (50% seizure reduction) rates were between 40 and 50%, as were mean overall seizure reduction rates. All controlled trials have shown statistically significant seizure reductions in VGB treated patients (20)(21)(22)(23)(24)(25)(26)(27)(28).…”

Section: Efficacymentioning

confidence: 99%

Vigabatrin

French

1999

Epilepsia

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Summary: Vigabatrin (VGB) is a structural analogue of the inhibitory neurotransmitter y-amino butyric acid (GABA), which produces its antiepileptic effect by irreversibly inhibiting the degradative enzyme GABA-transaminase. This produces an increase in central nervous system (CNS) GABA levels. VGB is among the few antiepileptic drugs (AEDs) that was synthesized with a specific targeted mechanism in mind and was subsequently demonstrated to function by that mechanism. Ti- HISTORY AND MECHANISM OF ACTIONVigabatrin (VGB) was first synthesized in the 1970s and was used clinically for the first time in 1979. Therefore, the clinical experience with this drug spans a longer time period than most of the new AEDs. VGB is approved for use in over 50 countries worldwide, and it is estimated that 175,000 patients have been exposed to the drug. The efficacy of VGB is well known, both in partial epilepsy and in some pediatric epilepsy syndromes.VGB consists of a racemic mixture of R-and Senantiomers. The R-enantiomer is completely inactive (1). It is presumed that the pharmacologic and toxic effects of vigabatrin are produced by the S-enantiomer.The primary mechanism of action of VGB is believed to arise from irreversible inhibition of GABA-transaminase, producing an increase in brain GABA. Experimental evidence demonstrates a clear relationship between brain GABA levels and seizures. Patients with partial epilepsy have lower mean brain GABA levels than controls. In investigations performed with magnetic resonance spectroscopy (MRS), there was a significant correlation between low GABA levels and recent seizures. Well-controlled epilepsy patients had higher mean brain GABA levels than those who were poorly controlled (2). In addition, when GABA levels are measured with implanted microdialysis catheters in patients with temporal lobe epilepsy undergoing presurgical evalua-

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Double‐Blind, Placebo‐Controlled Study of Vigabatrin (Gamma‐Vinyl GABA) in Drug‐Resistant Epilepsy

Cited by 130 publications

References 19 publications

The effect of different vigabatrin treatment regimens on CSF biochemistry and seizure control in epileptic patients.

The effect of different vigabatrin treatment regimens on CSF biochemistry and seizure control in epileptic patients.

Inhibition of the enzyme, GABA‐aminotransferase in human platelets by vigabatrin, a potential antiepileptic drug.

Vigabatrin

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