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

The ability of midbrain homogenates from two strains of mice to accumulate several putative neurotransmitters, or their precursor in the case of acetylcholine, has been examined. The high-affinity transport mechanisms toward glutamate, GABA, dopamine, and glycine were similar in both strains. The seizure-prone DBA21BG strain had a significantly higher capacity to transport choline than did the relatively seizure-resistant C57BL/6 IBC mice. Howaver, no difference in the density of muscarinic binding sites in the two mouse strains was found.
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PMID:Seizure proneness and neurotransmitter uptake. 4 44

The mechanisms of petit mal epilepsy remain a mystery despite successful therapy. Previous workers have proposed that paroxysmal activity of cortical inhibitory systems plays a role in absence seizures. In this study, we have compared the effects of bicuculline, a potent convulsive agent and GABA antagonist, with ethosuximide, a drug used to treat petit mal epilepsy, on the thalamocortical motor system of the cat. Under chloralose anesthesia, sequential pairs of pulses were delivered to ventrolateral thalamus (VL) varying either pulse amplitude or interval. The evoked responses were recorded from sensorimotor cortex, analyzed on-line by computer, and plotted as an excitability curve (mean response amplitude as a function of pulse interval), or a family of threshold curves (mean response amplitude as a function of stimulus amplitude at various fixed intervals). Administration of each drug resulted in increased thalamocortical excitability and decreased threshold to stimulation for short pulse-pair intervals, with diminished duration of the excitability curve. Increased alertness was produced by both drugs. Studies with grand mal anticonvulsants demonstrated entirely different effects. Because GABA is thought to be the primary inhibitory transmitter in VL and cerebral cortex, bicuculline would be expected to result in disinhibition. The similarity of the data for ethosuximide suggests that ethosuximide also suppresses inhibition in the thalamocortical motor system and adds further to the accumulating evidence of the role of inhibitory system in petit mal epilepsy.
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PMID:Ethosuximide and bicuculline inhibition in petit mal epilepsy. 9 76

The anticonvulsant potency and neurological toxicity of two new catalytic inhibitors of GABA-transaminase have been assessed in acute experiments in baboons with a natural syndrome of photic epilepsy. gamma-Acetylenic GABA, 160--200 mg/kg, or gamma-vinyl GABA, 450--950 mg/kg, intravenously, gave complete protection against generalised myoclonus or seizure responses induced by photic stimulation (in baboons without or with priming with subconvulsant doses of allylglycine). The protection became maximal 1--3 h after injection, and continued for 7--24 h. Signs characteristic of the acute toxicity of anticonvulsant drugs (nystagmus and ataxia) were not seen. The potential use of these compounds in human epilepsy deserves investigation.
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PMID:Blockade of epileptic responses in the photosensitive baboon, Papio papio, by two irreversible inhibitors of GABA-transaminase, gamma-acetylenic GABA (4-amino-hex-5-ynoic acid) and gamma-vinyl GABA (4-amino-hex-5-enoic acid). 10 Aug 12

The biochemical and behavioral effects of the anticonvulsant amino-oxyacetic acid (AOAA) have been studied in a model of focal penicillin seizures in rats. At 20 mg/Kg AOAA treatment results in a progressive 11 fold increase in GABA levels in cortex over three hours. There is a decrease in aspartate, ketoglutarate, alanine and glutamine, and an initial decrease followed by an increase in pyruvate and glutamate. These results reflect a functional inhibition of several B-6 dependent aminotransferase enzymes. When rats are pretreated 30 min before the onset of focal penicillin seizures there is a 60% reduction in the number of discharges and a 34% reduction in seizure duration. Pretreatment beyond 75 min results in progressively less anticonvulsant effect, such that seizures eventually become more severe than control. There is an increase in the number and duration of discharges, seizure spikes become complex, and tonic-clonic events develop. Penicillin seizures do not cause a change in levels of GABA, but result in a decrease in glutamate within the focus. AOAA pretreatment initially prevents this decrease in glutamate but later accentuates it. The biochemical effects of AOAA are complex, but biphasic anticonvulsant properties coincide in time with a change in the balance of excitatory and inhibitory amino acids in the seizure focus.
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PMID:Effect of amino-oxyacetic acid (AOAA) on focal penicillin seizures. 10 8

The effect of manipulation of GABA mechanisms in the region of the nucleus accumbens on dopamine-dependent locomotor hyperactivity in the rat has been studied. Two models of hyperactivity were used: (1) the injection of dopamine into the region of the nucleus accumbens in nialamide-pretreated animals and (2) the systemic administration of d-amphetamine. Both GABA and the GABA agonist 3-aminopropane sulphonic acid (3-APS) depressed hyperactivity in a dose-related manner. High concentrations of GABA (greater than 100 micrograms) were required to produce a significant effect and the response was short-lived possibly reflecting the efficient GABA inactivating mechanisms. 3-APS proved to be approximately 10 times more potent as compared to GABA in the dopamine-accumbens hyperactivity model. Conversely GABA receptor antagonism with low doses of either picrotoxin or bicuculline enhanced the mild locomotor response induced by a low dose of dopamine injected into the nucleus accumbens. However such results were difficult to evaluate fairly as higher doses of the GABA antagonists resulted in varying degrees of generalized seizures. Blockade of GABA uptake systems with cis-1, 3-aminocyclohexane carboxylic acid (ACHC), nipecotic acid or beta-alanine within the region of the nucleus accumbens produced dose-related depression of dopamine-dependent hyperactivity in both models. GABA uptake blockade (nipecotic acid) significantly enhanced the GABA-mediated depression of hyperactivity induced by bilateral injection of dopamine into the nucleus accumbens. The results demonstrate an inhibitory action of GABA and drugs facilitating GABA-ergic transmission on dopamine-dependent hyperactivity in the rat. Although open to criticisms of not being able to distinguish between true GABA effects and the results of non-specific neuronal depression the hyperactivity model underlines the potency of the GABA uptake blocking compounds and their possible potential for future clinical use.
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PMID:Dopamine-dependent hyperactivity in the rat following manipulation of GABA mechanisms in the region of the nucleus accumbens. 11 17

In experiments on male albino mice it has been established that upon intracerebroventricular administration in doses of 50, 100 and 300 mug per mouse GABA markedly inhibits the convulsive-seizure reactions in pentylenetetrazol and electroconvulsions and has no substantial effect on strychnine convulsions (the dose of 300 mug is toxic). Diethyldithiocarbamate (DDC) in a dose of 400 mg/kg, introduced i.p. 3 hours in advance, increases the convulsive reactivity in pentylenetetrazol and electroconvulsions. On the background of DDC the inhibitory effect of GABA is expressed only in antagonizing of the DDC effect increasing the convulsive reactivity. Alpha-methyl-paratyrosine (a-MT) in a dose of 250 mg/kg, introduced i.p. 4 hours in advance, has no substantial effect on the convulsive reactivity. On the background of alpha-MT the inhibitory effect of GABA in electroconvulsions does not change essentially, however, in pentylenetetrazol convulsions the GABA effect is practically not manifested. The results obtained show that the changes in the correlations between the catecholamines and GABA in the central nervous system result in substantial changes in the convulsive-seizure reactivity. The lower catecholamines level does not permit the marked manifestation of the GABA inhibitory effect. However, GABA counteracts to a certain extent the rise in the convulsive reactivity as a result of the drop in the brain level of the catecholamines.
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PMID:On certain relationships between gamma-aminobutyric acid (GABA) and adrenergic mechanisms in convulsive-seizure reaction. 18 73

gamma-Acetylenic GABA and gamma-vinyl GABA, two catalytic irreversible inhibitors of mammalian brain GABA transaminase that produce several-fold increases in brain GABA concentrations were tested for their effects on bicuculline and picrotoxin-induced seizures and mortality in mice. Neither inhibitor influenced the frequency of seizures or death produced by either bicuculline or picrotoxin. Both inhibitors, however, produced a dose-dependent prolongation of the time to onset of seizures and death induced by picrotoxin but by bicuculline. These results suggest differences in the antagonism by bicuculline and picrotoxin of GABA-mediated neural functions.
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PMID:Effect of elevated brain GABA concentrations on the actions of bicuculline and picrotoxin in mice. 20 Sep 66

Naloxone in high doses (60--240 mg/kg i.p.) produced a dose-dependent increase in cerebellar cGMP content of mice. The rise in cGMP content reached its maximum within 5 min and was of short duration. Short-lasting episodes of clonic seizures were noted after 240 mg/kg naloxone. Low doses of naloxone (5--10 mg/kg) had no effect on cerebellar cGMP content, but markedly potentiated the increase in cGMP induced by isoniazid. On the other hand, naloxone (5 mg/kg) partially antagonized the fall in cGMP elicited by diazepam, but had only a slight effect on the action of pentobarbital (30 mg/kg i.p.). These results support the assumption proposed by other authors that naloxone exerts GABA antagonistic effects aside from the potent opiate receptor antagonistic activity.
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PMID:The effect of naloxone on cerebellar cGMP content. A possible GABA-antagonistic action? 22 44

A decrease in brain GABA concentration has been implied as the cause of convulsions induced by hyperbaric oxygen (HOP). We therefore examined the influence of sodium valproate, an anticonvulsant and GABA transaminase inhibitor on HOP-induced convulsions in rats. The mean latency of occurrence of the first electrical discharge in the ECoG and the appearance of the first clinical seizure in awake chronically implanted rats was unchanged by administration of sodium valproate prior to HOP exposure. We conclude that either the sodium valproate inhibition of GABA removal is insufficient to compensate for HOP inhibition of its production, or else that GABA concentration changes are not causally related to HOP-induced seizures.
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PMID:Influence of a GABA transaminase inhibitor on central nervous system oxygen toxicity. 35 31

Experimental procedures are described which are believed to yield results that reflect, within certain limits, the in vivo changes of the size of the GABA pool in nerve endings in comparison with those of all other GABA pools. Two irreversible GABA-T inhibitors, vinyl GABA and acetylenic GABA, two GAD inhibitors, 3-mercaptopropionic acid and pyridoxal phosphate glutamyl-gamma-hydrazone, and di-n propylacetate, a clinically useful anticonvulsant, have been studied to determine their effects on GABA compartmentalization in mouse brain cortex. The changes elicited by these drugs in subcellular fractions of brain cortex homogenates support the notion that measurement of amino acid concentrations in crude synaptosomal fractions and in supernatant fractions under controlled conditions allow one to draw conclusions about relative changes of pool sizes in vivo. In particular this work showed that a specific increase in the concentration of GABA within the nerve endings is more important than a large increase of total brain GABA as a means of decreasing susceptibility to a variety of chemically or physically induced seizures.
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PMID:Metabolic inhibitors and subcellular distribution of GABA. 39 22


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