Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P80404 (GABA transaminase)
 786 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four inhibitors of gamma-aminobutyric acid transaminase (GABA-T) were investigated together with respect to their effects on hole-board exploration and temperature and the relation with effects on quasi-morphine-abstinence behaviour induced by dipropylacetate (DPA) in rats. Amino-oxyacetic acid (AOAA), gamma-acetylenic-GABA (GAG), gamma-vinyl-GABA (GVC) and ethanolamine-O-sulfate (EOS) were found to reduce hole-board exploration especially in the higher doses used, although the time-course of the effect was different for the compounds. For EOS and GVG the decrease in hole-board exploration paralleled a strong hypothermic effect. The compounds AOAA and GAG exerted a less and more transient hypothermic effect. However, the decrease in hole-board exploration did not fall in with this decrease in temperature. AOAA and GAG were found to decrease DPA-induced body shakes and locomotor activity, while GVG and EOS had no effect on body shakes and transient effects but opposite to each other, on locomotor activity. The efficacy of the GABA-T-inhibitors was measured biochemically, and the influence on the activity of glutamate decarboxylase (GAD) was also determined. AOAA and GAG were found to be strong inhibitors of GABA-T whereas the other two compounds were less efficient in the used doses. In addition AOAA and GAG influenced the activity of GAD strongly, while using GVG only a small decrease was found. The results suggest that the anti-quasi-withdrawal, the sedative and the hypothermic effects are not related to each other nor related to an effect on GABA-T. The suppressive effects on quasi-withdrawal body shakes, however, could be related to the inhibition of GAD and a hypothesis involving a compartmentalized action of DPA on GABA-metabolism has been proposed.
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PMID:Effects of inhibitors of GABA-transaminase on hole-board exploration and on temperature. Relation with effects on quasi-morphine abstinence behaviour induced by sodium dipropylacetate. 393 14

gamma-Vinyl GABA (gamma-aminobutyric acid), a drug that increases brain GABA via GABA transaminase inhibition, was evaluated in a blind, placebo-controlled trial in 10 patients with stable tardive dyskinesia. Drug effects during active treatment (2 to 6 g/day) and during pre- and posttreatment placebo periods were determined by scoring randomly sequenced videotapes of tardive dyskinesia and parkinsonian symptoms recorded weekly during standardized examinations. Tardive dyskinesia was significantly reduced, and correlated to increased parkinsonism. Eye blinking rates decreased, but psychiatric symptoms were unchanged during treatment.
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PMID:Effect of gamma-vinyl GABA in tardive dyskinesia. 613 54

The effects of bilateral microinjection of gamma-vinyl GABA (GVG, an irreversible inhibitor of GABA-T) were tested during the development of seizures induced by i.p. administration of 10 mg/kg of kainic acid. Intrahippocampal injection of GVG prevents the development of the seizures at an early stage in about half of the cases. In the remaining animals status epilepticus comparable to that of controls develops. Intra-amygdaloid injection reduces the severity of the seizures from the first motor limbic signs. Finally, intranigral injection prevents the appearance of convulsive status epilepticus or, when it develops, reduces its duration. The role that these three structures could play in the electro-clinical development of kainic acid-induced seizures is discussed.
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PMID:[Role of the hippocampus, amygdala and the substantia nigra in the evolution of status epilepticus induced by systemic injection of kainic acid in the rat]. 652 78

gamma-Vinyl GABA, an irreversible inhibitor of GABA transaminase, was administered orally to five patients with catatonic or hebephreno-catatonic schizophrenia. Improvement of psychiatric symptoms was observed in four cases. The results are discussed in relation to previously reported attempts to increase the CNS gabaergic function of patients with schizophrenia.
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PMID:[Effects of gamma-vinyl GABA per os in 5 cases of hebephreno-catatonic schizophrenia]. 664 16

Vigabatrin (VGB) is an antiepileptic drug (AED) that acts by irreversibly inhibiting gamma-aminobutyric acid transaminase (GABA-T). To evaluate immune responses to GVG, we studied 29 idiopathic or symptomatic epileptic children and also examined a control group (n = 15). Epileptic children were tested before and after 1 and 3 months of VGB treatment. Whole blood was used to connect subsets with commercial monoclonal antibodies. Peripheral blood mononuclear cells (PBMC) were used to assess natural killer (NK) cell activity and lymphocyte response to phytohemagglutinin (PHA) and concavalin A (Con A). Immunoglobulin (Ig) levels were tested in serum. At baseline, no immunologic abnormalities were observed in either control or treated patients. During treatment, the percentage and absolute number of B lymphocytes, serum concentration of Ig, number of T total mature lymphocytes (CD3), T-rosetting lymphocytes (CD11), T-helper cells (CD4), and mitogenic response of lymphocytes remained unchanged. Several other immunologic responses showed a statistically significant increase after 1 and 3 months of VGB treatment, however, including the percentage and absolute number of T-suppressor cells (CD8) and NK cells and NK cell activity. The correlation between number of NK cells and NK cell activity was significant. Data obtained demonstrated that VGB may interfere with the modulation of the immune system, especially cytotoxic cell populations.
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PMID:Immunologic aspects of vigabatrin treatment in epileptic children. 760 23

Vigabatrin (gamma-vinyl-GABA or GVG) is an irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T), which is an enzyme responsible for gamma-aminobutyric acid (GABA) catabolism. Inhibition of GABA catabolism increases brain concentration of GABA, a neural inhibitor. GVG has been found to be a potent new anti-epileptic drug, especially in the treatment of refractory epilepsy, in particular of complex partial seizures. Three patients who developed a severe status epilepitus while on GVG treatment are reported. A possible proconvulsive effect of GVG is hypothesized, which might result from disinhibition in the nigro-collicular pathway due to increased GABA-levels.
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PMID:Status epilepticus during vigabatrin treatment: a report of three cases. 767 Jul 70

The novel antiepileptic drug vigabatrin (Sabril) acts by inhibiting degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), increasing the GABA concentrations in the brain. Because the GABA degrading enzyme GABA aminotransferase (GABA-T) is also present in peripheral tissues, including blood platelets, measurement of plasma GABA levels might be a useful indication of the pharmacological response to vigabatrin during therapeutic monitoring. However, because of the very low concentrations of GABA in plasma, the few methods available for plasma GABA analysis are time-consuming, difficult to perform and/or not selective enough because of potential interference with other plasma constituents. In the present study, a rapid, selective and sensitive amino acid analysis HPLC method has been developed for plasma GABA determination with fluorescence detection, using o-phthaldialdehyde as a precolumn derivatizing agent. By employing a 3 microns particle size reversed-phase column and a multi-step gradient system of two solvents, the very low endogenous concentration of GABA in human plasma could be reproducibly quantitated without interference of other endogenous compounds. Incubation of human plasma samples with GABA degrading enzyme(s) resulted in an almost total loss of the GABA peak, thus demonstrating the specificity of the method for GABA analysis. In addition to GABA and other endogenous amino acids, the HPLC method could be used to quantitate plasma levels of vigabatrin. Thus, this improved HPLC amino acid assay might be used to examine whether concomitant monitoring of plasma GABA and vigabatrin is useful for clinical purposes. This was examined in 20 epileptic patients undergoing chronic treatment with vigabatrin. The average plasma GABA level of these 20 patients did not differ significantly from non-epileptic controls. However, when epileptic patients were subdivided according to their clinical response to vigabatrin, vigabatrin responders had significantly higher GABA levels than nonresponders or controls. In contrast to the difference in plasma GABA, vigabatrin responders and nonresponders did not differ in dose or plasma level of vigabatrin. These data may indicate that determination of plasma GABA is a valuable non-invasive method for therapeutic monitoring in patients on medication with vigabatrin.
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PMID: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. 850 95

Gamma-vinyl GABA (GVG, also referred to as vigabatrin), an irreversible inhibitor of GABA transaminase (GABA-T), raises levels of GABA in nerve terminals, inhibits striatal dopamine release, and attenuates cocaine-induced increases in extracellular dopamine in the striatum and nucleus accumbens. In order to determine the action of GVG on dopamine-mediated reward, we examined its effects on the threshold for rewarding brain stimulation in male F-344 rats. GVG dose-dependently raised brain stimulation reward (BSR) thresholds at doses of 200, 300, and 400 mg/kg without significant effects on motor performance as measured by response latencies. In order to determine if GVG had similar modulatory effects on cocaine-induced lowering of BSR thresholds, the effective doses of GVG were co-administered with 2.5 and 5.0 mg/kg cocaine, doses that significantly lower BSR thresholds. The 400 mg/kg dose of GVG significantly blocked the lowering of thresholds seen at each dose of cocaine. Cocaine in combination with 200 or 300 mg/kg GVG, doses of GVG that significantly raise BSR thresholds, resulted in thresholds not significantly different from those obtained with cocaine alone. These data demonstrate that, at the doses tested, GVG is more effective at modulating basal reward thresholds that at modulating thresholds lowered by cocaine, implying that as dopaminergic activity increases, GABAergic activity must also increase in order to exert its inhibitory influence on dopaminergic activity.
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PMID:Gamma-vinyl GABA attenuates cocaine-induced lowering of brain stimulation reward thresholds. 937 39

Previous studies have demonstrated that the expression of one of the isoforms of glutamate decarboxylase, GAD67, is selectively reduced in cultured cortical neurons and in rat cerebral cortex when the concentration of GABA is elevated. We asked whether the expression of GAD67 was similarly affected by elevated GABA throughout the brain. The concentration of GABA in rat brain was increased by inhibiting GABA transaminase (GABA-T) with vigabatrin (gamma-vinylGABA, GVG), an antiepileptic drug and selective inhibitor of GABA-T. Rats were injected with saline or vigabatrin (150 mg/kg) daily for 5 days, and the effects of accumulated GABA on total GAD activity and the expression of GAD65 and GAD67 proteins were determined in twelve brain regions. The GABA concentration was significantly elevated in all regions except amygdala and olfactory bulb after vigabatrin treatment. Total GAD activity was significantly lower than controls in six regions: cerebellum, frontal cortex, thalamus, substantia nigra, ventral tegmentum, and the remaining midbrain. The decrease in GAD activity was largest in cerebellum and thalamus (33% and 29%), while the changes in the other four areas were 15-18%. Vigabatrin treatment significantly reduced GAD67 protein in all regions except olfactory bulb, whereas GAD65 protein decreased significantly only in cerebellum. The failure to detect significant changes in GAD activity in regions having a significant change in GAD67 levels is attributable to the small contribution of GAD67 to total GAD in those regions. It is evident that there are marked regional differences in the effects of tissue GABA levels on the expression of GAD67.
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PMID:Elevation of brain GABA levels with vigabatrin (gamma-vinylGABA) differentially affects GAD65 and GAD67 expression in various regions of rat brain. 966 22

gamma-Vinyl gamma-aminobutyric acid (GABA) (GVG) is an irreversible inhibitor of GABA transaminase, the primary enzyme involved in GABA metabolism. Acute administration of GVG increases brain GABA levels and blocks cocaine-induced locomotor activity, cocaine-induced lowering of brain stimulation reward thresholds, and cocaine-induced conditioned place preference. To further evaluate the effects of GVG on cocaine-induced reward, we examined its effects on cocaine self-administration in male Wistar rats on fixed ratio 5 and progressive ratio schedules of reinforcement. Additionally, the effects of GVG on operant responding for a food reward were examined on the same two schedules to determine whether the effects of GVG were specific to cocaine reward or generalized to other types of reward. GVG dose dependently decreased responding for cocaine on both schedules of reinforcement, suggesting that GVG attenuated the reward value of the cocaine. Responding for food was also decreased by GVG, suggesting that the effects of increased GABA levels induced by GVG may have a general effect on central reward systems. Data from this and other studies indicate that GVG does not induce motor impairment, decrease spontaneous locomotor activity, or induce catalepsy. Taken together, these data suggest that increases in GABAergic activity induced by GVG have an attenuating effect on centrally mediated reward systems and that the GABA system may be a useful target in the development of new therapeutic strategies for cocaine addiction.
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PMID:The irreversible gamma-aminobutyric acid (GABA) transaminase inhibitor gamma-vinyl-GABA blocks cocaine self-administration in rats. 1041 94


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