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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of pentobarbital and phenytoin on the high-affinity uptake of the putative neurotransmitters gamma-aminobutyric acid (GABA), glutamate, and norepinephrine was examined in synaptosomes prepared from rat brain. Both pentobarbital and phenytoin inhibited the uptake of norepinephrine. Pentobarbital increased the uptake of GABA twofold and only slightly increased the uptake of glutamate. Phenytoin facilitated GABA uptake to a lesser extent than did pentobarbital, but also increased the uptake of glutamate. This suggests that these drugs may limit the propagation of seizures through the balance of excitatory glutamate pathways and inhibitory GABA and norepinephrine pathways. The contrasting effects of these drugs on GABA and glutamate uptake may be related to the hypnotic properties of pentobarbital not present in phenytoin.
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PMID:Mechanism of action of anticonvulsants. Role of the differential effects on the active uptake of putative neurotransmitters. 0 91

Using an immunocytochemical method for the localization of the gamma-aminobutyric acid (GABA) synthesizing enzyme, glutamic acid decarboxylase (GAD), we have observed GABAergic nerve terminals distributed throughout all layers of normal monkey sensorimotor cortex. These terminals displayed ultrastructural characteristics that suggested that they arose from aspinous and sparsely spinous stellate neurons. In monkeys (Macaca mulatta and M. fascicularis) made epileptic by cortical application of alumina gel, a highly significant numerical decrease of GAD-positive nerve terminals occurred at sites of seizure foci indicating a functional loss of GABAergic inhibitory synapses. A loss of such inhibition at seizure foci could lead to epileptic activity of cortical pyramidal neurons.
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PMID:Inhibitory, GABAergic nerve terminals decrease at sites of focal epilepsy. 10 22

The time course of changes in behaviour, seizure response and cerebral monoamine and gamma-aminobutyric acid (GABA) metabolism has been studied in relation to the anticonvulsant actions of di-n-propylacetic acid (DPA) and ethanolamine-O-sulphate (EOS) on sound-induced seizures in DBA/2 mice. Changes in cerebral monoamine metabolism after EOS (75 or 150 mug, intracerebroventricularly) were not related to its anticonvulsant action. The primary effect was GABA-transaminase inhibition (by 50-70%) leading to a 2-4 fold increase in cerebral GABA concentration. Increases in brain GABA concentration (maximally 36%), 5-hydroxyindoleacetic acid (5HIAA, maximally 134%) and homovanillic acid (HVA, maximally 183%) were seen after DPA (400-600 mg/kg, i.p.). The time course of the increases in HVA and 5HIAA did not correlate with the anticonvulsant effect. Elimination of these increases by the use of inhibitors of monoamine synthesis (alpha-methyl-p-tyrosine and p-chlorophenyl-alanine) did not alter the anticonvulsant effect of DPA. Experiments using probenecid suggested that the increases in 5HIAA and HVA after DPA result from inhibition of their active transport out of the brain.
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PMID:Monoamine and GABA metabolism and the anticonvulsant action of di-n-propylacetate and ethanolamine-O-sulphate. 13 17

Lumbar cerebrospinal fluid (CSF) gamma-aminobutyric acid (GABA) levels determined by fluorometric assay in four seizure patients were found to be significantly lower during bilateral, continuous cerebellar stimulation than those determined after a 7-day period without stimulation. The CSF GABA concentrations during chronic unilateral, alternating cerebellar stimulation were reduced in three seizure patients but unchanged in a fourth patient. The percentage decrease in CSF GABA appeared to be independent of cerebellar stimulation frequency. These findings suggest that GABA-mediated neuronal transmission is depressed during cerebellar surface stimulation and this evoked reduction in GABA activity may compromise the efficacy of cerebellar stimulation in the treatment of epilepsy. Lumbar CSF cyclic guanosine monophosphate levels determined by radioimmunoassay were not significantly altered by either mode or frequency of cerebellar stimulation.
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PMID:Cerebrospinal fluid GABA reductions in seizure patients evoked by cerebellar surface stimulation. 19 17

The hypothesis that the seizure susceptibility of chronically denervated cortex is due to interruption of recurrent inhibitory pathways was tested by examining the release of 3H-labeled gamma-aminobutyric acid ([3H]GABA) from chronic slabs and normal cortex of cats. Seizure activity was maintained throughout the test periods in both normal and chronically isolated cortex. When methacholine was used to evoke seizure activity, [3H]GABA release was depressed in both normal and epileptic cortex, suggesting that the mechanism of seizure genesis by cholinomimetics involves suppression of inhibitory neuron activity. Pentylenetetrazol-induced seizures evoked a small, equal increase in [3H]GABA efflux from epileptic and normal cortex. Continuous electrical stimulation evoked a large, and again equal increase in [3H]GABA release. Preseizure efflux of [3H]GABA was the same from chronic slabs and normal cortex in all experiments. Since the interruption of recurrent inhibitory pathways by chronic denervation would result in a decreased resting and seizure-evoked release of [3H]GABA, results obtained do not support the above-mentioned hypothesis.
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PMID:Release of exogenous gamma-[3H]aminobutyric acid during seizure activity in chronically denervated and normal cat cortex. 49 93

Anticonvulsants were tested on mice for their effectiveness against different chemical convulsants. Ethosuximide is very effective against pentylenetetrazol (PTZ), but ineffective against 3-mercaptopropionate (3-MP) which is an inhibitor of gamma-aminobutyrate (GABA) synthesis. Trimethadione, chlordiazepoxide and mesuximide are less effective against 3-MP than against PTZ. The same tendency was apparent, though falling short of statistical significance, with phenobarbital, mephenytoin, carbamazepine and valproic acid, whereas aminooxyacetic acid (AOAA) appeared to be somewhat more effective against 3-MP than against PTZ. Several anticonvulsants were tested also against bicuculline (BIC), picrotoxin (PIC) and bemegride (BEM), and profiles depicting their relative capacities to antagonize the convulsants were constructed. These show major differences and few resemblances. Likewise the convulsants show little resemblance to each other in their patterns of sensitivity to different anticonvulsants. The data do not support the concept that PTZ, BEM, BIC or PIC induce seizures primarily by blockading GABA-mediated inhibition, since their patterns are so unlike that of 3-MP. The profiles of clinically used anticonvulsants suggest that none of those tested acts primarily on the GABA system, since all are so unlike that of AOAA.
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PMID:Quantitative evaluation of the actions of anticonvulsants against different chemical convulsants. 50 98

Mice were made physically dependent on ethanol by a 3-day period of alcohol inhalation with small daily injections of pyrazole. During this treatment the concentrations of norepinephrine, dopamine and 5-hydroxytryptamine were increased in brain with concomitant decrease in gamma-aminobutyric acid, RNA and DNA. However, the monoamine concentrations showed complete regression to normal levels at the time of maximal withdrawal seizure when GABA level was still elevated above the control values. Brain RNA and DNA concentrations remained low at this period. During the recovery phase, the pattern of neuronal components was almost the same as was observed at maximal withdrawal seizures. Pyrazole by itself did not produce significant changes in concentrations of the neuronal components of brain.
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PMID:Neurochemical aspects of ethanol dependence and withdrawal reactions in mice. 55 9

The anticonvulsant effect of di-n-propylacetic acid (n-DPA) was studied in mice and compared to those of phenobarbital, trimethadione and ethosuximide. n-DPA was only weakly active in the maximal electroshock test, but had an ED50 of 420 mg/kg orally in the pentetrazole seizure threshold test, which corresponds rather well to the activity of trimethadione and ethosuximide. The duration of action was only short, and the first signs of neurotoxicity--inability to perform in the chimney test--appeared well below the anticonvulsant ED50 against pentetrazole. n-DPA proved to be most active against convulsions induced by picrotoxin (ED50 200 mg/kg orally), which might indicate a role of the elevation of the central levels of gamma-aminobutyric acid in the anticonvulsant effect of the drug.
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PMID:Di-n-propylacetic acid--profile of anticonvulsant activity in mice. 77 4

gamma-Acetylenic gamma-aminobutyric acid (gamma-acetylenic GABA) produces several-fold sustained elevations of brain GABA concentrations when administered intraperitoneally to mice. It protects mice against seizures induced by audiogenic stimuli, electroshock, thiosemicarbazide, isoniazid and strychnine. The duration and degree of audiogenic seizure protection appears to correlate with elevations in whole brain GABA levels. gamma-Acetylenic GABA does not protect against seizures induced by pentylenetetrazol or picrotoxin even at doses that increase brain GABA concentrations approximately 6-fold. This differential antiseizure activity suggests that the GABA system may play a role in some, but not all experimentally produced seizures.
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PMID:Antiseizure activity of gamma-acetylenic gamma-aminobutyric acid: a catalytic irreversible inhibitor of gamma-aminobutyric acid transaminase. 86 98

Susceptibility to audiogenic seizures can be induced in some strains of resistant mice by exposure to an initial auditory stimulus (acoustic priming). Aminooxyacetic acid, hydrazine, glutamic acid, gamma-aminobutyric acid (GABA), cycloheximide, and metyrapone antagonize the acoustic priming of audiogenic seizure susceptibility in C57BL/6Bg mice, whereas only metyrapone attenuates that of DBA/1Bg-asr mice. The strain difference in the effect of AOAA and cycloheximide is correlated with a small, transient fall in level of brain GABA in C57BL/6Bg but not DBA41Bg-asr mice. These findings support our hypothesis that there are at least two neural mechanisms of acoustic priming, each with its own genetic basis and that corticosteroids are required by both mechanisms for the development of primed seizures.
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PMID:Pharmacogenetic differences in audiogenic seizure priming of C57BL/6Bg and DBA/1Bg-asr mice. 92 78


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