Disease relevance of Sabril

• We found therapeutic intervention with phenobarbital or phenytoin ineffective, whereas intervention with vigabatrin or the GABAB receptor antagonist CGP 35348 (ref. 2) prevented tonic-clonic convulsions and significantly enhanced survival of the mutant mice [1].
• Vigabatrin in infantile spasms [2].
• METHODS: We enrolled 459 patients with newly diagnosed, previously untreated partial epileptic seizures from 44 European centres and randomly assigned them carbamazepine 600 mg daily (n=230) or vigabatrin 2 g daily (n=229) [3].
• INTERPRETATION: Vigabatrin seems less effective but better tolerated than carbamazepine, which is the first-choice drug for the treatment of partial epilepsies [3].
• Improvement of stiff-man syndrome with vigabatrin [4].

Psychiatry related information on Sabril

• Bipolar affective psychosis after vigabatrin [5].
• Thirty-seven patients discontinued vigabatrin for the following reasons: benefit-to-risk evaluation, 8; seizure breakthrough, 6; adverse events, 6; seizure breakthrough and adverse events, 5; moved or lost, 4; no longer eligible for study, 2; non-drug-related death, 2; narcotic abuse, 1; and patient request, three [6].
• We conducted a single-blind trial of gamma-vinyl-GABA (GVG) in nine patients: seven with tardive dyskinesia, one with Meige syndrome, and one with Tourette syndrome [7].
• Anxiolytic effects of vigabatrin in panic disorder [8].
• Vigabatrin and posttraumatic stress disorder [9].

High impact information on Sabril

• We report a girl with epilepsy aged 10 years receiving vigabatrin and complaining of bumping into objects and presenting visual-field constriction, which disappeared after vigabatrin withdrawal [10].
• Vigabatrin was better tolerated than carbamazepine with fewer withdrawals, but was more frequently associated with psychiatric symptoms (58 [25%] vs 34 [15%]) and weight gain (25 [11%] vs 12 [5%]) [3].
• Long follow-up of tuberous sclerosis treated with vigabatrin [11].
• Vigabatrin for startle-disease with altered cerebrospinal-fluid free gamma-aminobutyric acid [12].
• Vigabatrin, the GABA-transaminase inhibitor, damages cone photoreceptors in rats [13].

Chemical compound and disease context of Sabril

• Chronic administration of vigabatrin (gamma-vinyl GABA) in dogs produces reversible microvacuolation (intramyelinic edema) in discrete brain regions [14].
• In a small but well-controlled comparative trial, vigabatrin was as effective as baclofen in reducing spasm and improving some parameters of spasticity in patients with spinal cord lesions or multiple sclerosis [15].
• In the present study, we examined whether the elevation of GABA by gamma-vinyl-GABA protects cultured rat fetal hippocampal neurons against toxicity induced by a 20-min incubation with 100 microM L-glutamate [16].
• Many systemic drugs may produce ocular toxicity, including bisphosphonates, topiramate, vigabatrin, isotretinoin and other retinoids, amiodarone, ethambutol, chloroquine and hydroxychloroquine, tamoxifen, quetiapine, cyclo-oxygenase (COX)-2 inhibitors, erectile dysfunction agents and some herbal medications [17].
• Gabapentin but not vigabatrin is effective in the treatment of acquired nystagmus in multiple sclerosis: How valid is the GABAergic hypothesis [18]?

Biological context of Sabril

• In this study, we assessed visual fields, visual evoked potentials (VEPs), and electroretinography (ERG) in children treated with vigabatrin [19].
• Kinetics of the enantiomers of vigabatrin after an oral dose of the racemate or the active S-enantiomer [20].
• No clinically important changes in MRI, evoked potential, or other laboratory tests were noted during vigabatrin treatment [21].
• Some of the vigabatrin patients also had reduced visual acuity and abnormal color vision [22].
• Vigabatrin was well tolerated, compliance was high with twice-daily administration, and therapy did not result in clinically relevant drug interactions [21].

Anatomical context of Sabril

• Monitoring of 4-hydroxybutyric acid levels in body fluids during vigabatrin treatment in succinic semialdehyde dehydrogenase deficiency [23].
• Antiepileptic drugs that support the action of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the neocortex (vigabatrin, baclofen) reduced intracortical excitability but had no effect on motor threshold [24].
• This study suggests that the visual field loss in vigabatrin-treated epileptic patients may result from a sequence of events starting from cone cell injury to a more severe disorganization of the photoreceptor layer [13].
• Regulation of GAD expression in rat pancreatic islets and brain by gamma-vinyl-GABA and glucose [25].
• Using 1H spectroscopy, we measured occipital lobe GABA levels serially in 18 patients enrolled in an ongoing open label trial of vigabatrin [26].

Associations of Sabril with other chemical compounds

• The antiepileptic drug vigabatrin increases human cerebrospinal fluid homocarnosine linearly with daily dose [27].
• The neurotoxicity caused by Tat and gp120 applied in combination was blocked completely by memantine, partially by amiloride, and not at all by dipyridamole or vigabatrin [28].
• Furthermore, the pharmacokinetics of gabapentin, oxcarbazepine and vigabatrin are independent of concomitant drugs [29].
• Neither a 24-h pretreatment nor posttreatment with gamma-vinyl-GABA (100 microM) had any neuroprotective effects, as determined by counting microtubule-associated protein-2 positive cells and lactate dehydrogenase assay 24 h after the glutamate treatment [16].
• Degradation of GABA by GABA-transaminase (GABA-T) was blocked by gamma-vinyl-GABA (GVG) and synthesis of GABA through glutamate decarboxylase (GAD) was suppressed with 3-mercaptopropionic acid (MPA) [30].

Gene context of Sabril

• Vigabatrin transport across the human intestinal epithelial (Caco-2) brush-border membrane is via the H(+)-coupled amino-acid transporter hPAT1 [31].
• OBJECTIVE: To study the expression and role in vigabatrin (VGB)-induced gingival enlargement of Ki-67 antigen and p27KIP1, p21WAF1, and p53, proteins that activate or inhibit cell-cycle progression [32].
• Pharmacological therapy in patients with this disorder has been limited to vigabatrin, an anticonvulsant that blocks GABA transaminase [33].
• Effect of vigabatrin on glutamate dehydrogenase in the hippocampus of seizure prone gerbils [34].
• We conclude that vigabatrin in SSADH deficiency should be administered in a gradually increasing dosage combined with frequent evaluation of the clinical condition and the EEG [35].

Analytical, diagnostic and therapeutic context of Sabril

• Safety and efficacy of vigabatrin and carbamazepine in newly diagnosed epilepsy: a multicentre randomised double-blind study. Vigabatrin European Monotherapy Study Group [3].
• Perimetry seemed to be the most sensitive modality for identifying vigabatrin toxicity [19].
• EOG, a more sensitive diagnostic tool than ERG for screening vigabatrin-treated patients, also appears to be more specific [36].
• Based on this and other long-term data, clinical trials of vigabatrin have resumed in the United States and Canada [6].
• We enrolled 203 patients; 182 (90 placebo; 92 vigabatrin) received drug therapy under double-blind conditions [21].

References