Increased gamma-aminobutyric acid (GABA), homocarnosine and β-alanine in cerebrospinal fluid of patients treated with γ-vinyl GABA (4-amino-hex-5-enoic acid)

Grove, Jeffrey; Schechter, Paul J.; Tell, G.; Koch‐Weser, Jan; Sjoerdsma, Albert; Warter, Jean‐Marie; Marescaux, C.; Rumbach, L.

doi:10.1016/0024-3205(81)90511-7

Cited by 116 publications

(62 citation statements)

References 19 publications

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“…These results are consistent with the dose-dependent increases in these CSF constituents previously demonstrated following vigabatrin administered twice daily (Grove et al, 1981;Schechter et al, 1984) and with our previous study (BenMenachem et al, 1988) al., 1988). In contrast, no changes in CSF concentrations of HVA and 5-HIAA levels compared to baseline were found following either 4 weeks (Schechter, 1986) or 12 weeks of vigabatrin.…”

Section: Discussionsupporting

confidence: 93%

“…Vigabatrin represents the first effective anti-epileptic agent shown unequivocally to influence CNS GABA metabolism in man. Alterations in CSF GABA concentrations consistent with inhibition of central GABA-T occurred in every subject treated with vigabatrin in our study as well as in previous work (Grove et al, 1981;. However, it is clear that despite these universal CSF changes not all epileptic patients respond to a fixed dose of vigabatrin with decreased seizure frequency.…”

Section: Discussionsupporting

confidence: 87%

“…In all published studies to date vigabatrin has been administered orally on a twice-daily schedule. This frequency of dosing was chosen arbitrarily following the demonstration that it produced increases in CSF GABA concentrations in man (Grove et al, 1981;Schechter et al, 1984). We have recently shown, in a longitudinal study in 11 epileptic patients, that a single oral dose of vigabatrin increases lumbar CSF concentrations of free and total GABA and homocarnosine (GABA-histidine dipeptide) with concentrations remaining significantly elevated above pretreatment levels for 120 h (Ben Menachem et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

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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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“…As it is not practical to measure brain GABA-T activity or GABA concentration directly in humans, previous studies have investigated the measurement of cerebrospinal fluid (CSF) GABA concentration as a possible method of monitoring the pharmacological effect (Grove et al, 1981;Tell et al, 1981). In animals administration of vigabatrin elevates both brain and CSF GABA concentrations (Bohlen et al, 1979).…”

Section: Introductionmentioning

confidence: 99%

“…Administration of vigabatrin to patients with various neurological disorders results in dose-related increases in both total and free CSF GABA levels (Grove et al, 1981;Schechter et al, 1984). To date, no study has shown a relationship between the increase in CSF GABA concentration and clinical response in patients with epilepsy.…”

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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Double-blind Study of Vigabatrin in the Treatment of Drug-Resistant Epilepsy

Tassinari

Michelucci²,

Ambrosetto

et al. 1987

Archives of Neurology

137

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Increased gamma-aminobutyric acid (GABA), homocarnosine and β-alanine in cerebrospinal fluid of patients treated with γ-vinyl GABA (4-amino-hex-5-enoic acid)

Cited by 116 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.

Double-blind Study of Vigabatrin in the Treatment of Drug-Resistant Epilepsy

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