Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cDNA library was prepared from rabbit brain mRNA, in the expression vector, lambda gt11. The library was screened with polyclonal antibodies raised against the neurofilament protein NF-H, and a cloned cDNA (KMRH-1) was selected and characterized. The fusion protein coded for by KMRH-1 includes epitopes for two monoclonal antibodies which react with nonphosphorylated sites in the tail region of NF-H. The selected cDNA includes 891 base pairs. It hybridizes to human genomic DNA, as well as to rabbit genomic DNA, and to a rabbit brain mRNA with a size of 4.7 kilobases (kb). The sequence of KMRH-1 includes extensive repeating regions, including one duplicated 60-base segment. Within the first 196 bases, one 13-base segment is repeated 9 times. The cDNA codes for the carboxy-terminal 184 amino acid residues of NF-H, including a series of 9 serines, each surrounded by a similar group of amino acids: ..Ala.Lys.Ser.Pro.(Glu./Val.).Lys.. Comparison of the derived amino acid sequence for KMRH-1 indicates considerable divergence from the sequence information available for rodent NF-H (Robinson et al.: FEBS Lett 209:203-205, 1986). This diversity in amino acid sequence may account for the failure to induce tangles of neurofilaments in animals, such as rats, following treatment with doses of aluminum which are sufficient to induce such tangles in rabbits and to bring on seizures and behavioral pathology in both species.
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PMID:cDNA coding for the tail region of the high molecular weight rabbit neurofilament protein NF-H. 313 32

Beta-N-methylamino-L-alanine (BMAA) and beta-N-oxalylamino-L-alanine (BOAA) are chemically related amino acids present in the seeds of Cycas circinalis and Lathyrus sativus, respectively. Consumption of these seeds has been linked to Guam amyotrophic lateral sclerosis (BMAA) and lathyrism (BOAA; a form of primary lateral sclerosis). A single large dose of BOAA or BMAA causes seizures in newborn mice and postsynaptic neuronal edema and degeneration in CNS explants. We report that the acute neurotoxic actions of these amino acids are blocked selectively by specific glutamate-receptor antagonists (administered intracerebroventricularly) (i.c.v.) prior to the amino acid. Administration of BOAA i.c.v. to neonatal mice (ED100 = 50 micrograms) elicits a spectrum of time-dependent behavioral states including arm and leg rigidity, convulsions, and resting tremor. These are blocked in a dose-dependent manner by cis-2,3-piperidine dicarboxylic acid (PDA), an antagonist of quisqualate (QA)-preferring (A2) and kainate (KA)-preferring (A3) glutamate receptors (ED50s; 2.8 micrograms, rigidity; 1.4 micrograms, convulsions; 2.4 micrograms, resting tremor). BMAA induces a transitory hyperexcitable state followed by a long-lasting whole-body shake/wobble (ED100 = 1,000 micrograms, i.c.v.). These responses are antagonized selectively and dose-dependently by 2-amino-7-phosphonoheptanoic acid (AP7), an N-methyl-D-aspartate (NMDA) or A1 glutamate-receptor antagonist (ED50 = 0.45 microgram). Taken collectively, our data indicate that the acute neuronotoxic actions of BOAA and BMAA (or a metabolite) operate through different glutamate-receptor species. BMAA likely exerts most of its action indirectly via the A1 glutamate receptor, while BOAA acts principally at the A2 and/or A3 receptor.
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PMID:Specific antagonism of behavioral action of "uncommon" amino acids linked to motor-system diseases. 314 80

The effect of diazepam on inbred mutant E1 mice, which develop convulsive seizures after repeated sessions of being tossed up, was examined. Acute administration of diazepam (32 mg/kg, i.p.) completely inhibited the convulsions. At that time, the dopamine level was increased in the cortex and hippocampus, and the norepinephrine level in the cerebellum was decreased. 5-Hydroxytryptamine levels were not changed. As for amino acids, the glutamine level increased and the levels of GABA, glutamic acid, aspartic acid, alanine and other amino acids were not changed.
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PMID:Depressed convulsions by diazepam and its effects on brain monoamines and amino acids in E1 mice. 319 91

N-Acetyl-D,L-alanine-N-benzylamide and N-acetyl-D,L-phenylglycine-N-benzylamide are two novel anticonvulsants that selectively blocked maximal electric shock-induced tonic extensor seizures in mice. For both compounds, the anticonvulsant activity is due to the D-stereoisomer, and the L-stereoisomer is virtually inactive as an anticonvulsant. The marked stereoselectivity of these anticonvulsants may make them very useful pharmacological tools for the study of the mechanism(s) of anticonvulsants that selectively inhibit maximal electric shock-induced seizures.
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PMID:Marked stereospecificity in a new class of anticonvulsants. 321 63

CPP has a potent anticonvulsant effect against sound-induced seizures in audiogenic DBA/2 mice. Pretreatment with CPP (0.01-10 nmol i.c.v., 45 min) protects against successive phases of sound-induced seizures in a dose-dependent fashion (ED50, tonic phase, 0.023 nmol; clonic phase, 0.039 nmol; wild running, 0.17 nmol). Systemic administration of CPP (0.001-0.1 mmol/kg i.p., 45 min) produces a similar protection (ED50, tonic phase, 0.0012 mmol/kg; clonic phase, 0.0026 mmol/kg; wild running, 0.021 mmol/kg). Following the administration of a fully anticonvulsant dose of CPP (0.1 mmol/kg i.p., 45 min) to adult DBA/2 mice regional brain glucose (cerebellum and striatum) levels are elevated and lactate (striatum and hippocampus) levels decrease. The CPP-induced changes in alanine, serine and glycine paralleled those of lactate. Aspartate levels are significantly decreased by CPP in the striatum (-21%) and the hippocampus (-23%).
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PMID:Anticonvulsant action and biochemical effects in DBA/2 mice of CPP (3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate), a novel N-methyl-D-aspartate antagonist. 330 90

Biochemical and pharmacological effects of gamma-vinyl GABA (Vigabatrin, GVG), and irreversible enzyme-activated inhibitor of 4-aminobutyrate: 2-oxoglutarate aminotransferase (EC 2.6.1.19; GABA-T), were measured in mice. This anticonvulsant produced a time- and dose-dependent elevation of the GABA, phenylalanine and lysine contents of cortical tissue and simultaneously decreased glutamate, aspartate and alanine levels. In addition, GVG caused a biphasic change in glutamine concentrations (a decline 1-4 hours after administration, followed 20 hours later by an increase). Moreover, we found a new, as yet unidentified amino acid in the brain eluting with the same retention time as alpha-aminoadipic acid from an HPLC cation-exchange column. The level of this novel chemical entity was greatly increased by GVG 20 hours after injection of the drug. At all tested intervals between 1 and 60 hours after injection, GVG was ineffective against maximal electroshock. The GABA-T inhibitor dose-dependently protected mice against isoniazid-induced seizures, simultaneously causing an increase in brain GABA concentrations. However, this apparent correlation applied only until 4 hours after treatment. To better define the anticonvulsant profile of GVG, groups of mice were treated, 1, 2, 4, and 24 hours prior to challenge with convulsant doses of strychnine, pentetrazole (PTZ), and picrotoxin, and brain amino acid levels, including brain concentrations of GVG, were measured. In all instances, the time dependency of the anticonvulsant effects of GVG and of increases in brain GABA levels differed. Amino acid concentrations in animals treated only with GVG were similar to those in animals given GVG and a chemical convulsant. GVG showed no selectivity for seizures produced by impairment of GABA-ergic neurotransmission. Although GVG is an effective GABA-T inhibitor, it apparently affects several other pyridoxal-phosphate-dependent cerebral enzymes and/or interacts with other neurotransmitter systems as well.
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PMID:Gamma-vinyl GABA: comparison of neurochemical and anticonvulsant effects in mice. 341 34

To examine the hypothesis that hypoglycemia has an adverse effect on brain energy state during seizure, neonatal dogs were subjected to bicuculline-induced seizure while hyperglycemic, normoglycemic, or hypoglycemic. Cerebral blood flow increased and remained elevated in all animals subjected to seizure, regardless of blood or brain glucose concentration. In vivo 31P nuclear magnetic resonance spectroscopy disclosed a small (10-20%) decrease in adenosine triphosphate levels and a greater (20-40%) decline in phosphocreatine levels in animals experiencing seizure, irrespective of whether they were hyper-, normo-, or hypoglycemic. In vitro analysis of brain extracts with 1H nuclear magnetic resonance spectroscopy disclosed a significant elevation of lactate in all seizing animals. There were differences in brain alanine, glycine, and beta-hydroxybutyrate levels between the hyperglycemia-seizure and hypoglycemia-seizure groups. Alternate substrates such as lactate, fatty acids, or amino acids may be used when neonatal seizure is complicated by hypoglycemia, thereby preventing further deterioration of brain metabolic state.
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PMID:In vivo 31P and in vitro 1H nuclear magnetic resonance study of hypoglycemia during neonatal seizure. 342 68

Lumbar free CSF GABA and amino acid concentrations were measured in 43 patients with newly diagnosed untreated epilepsy and 26 patients with chronic drug-resistant epilepsy. The results were compared with those from 51 control patients. No differences in free CSF GABA concentration could be detected between patients with epilepsy, either treated or untreated, and controls. Untreated patients with primary generalised epilepsy and partial seizures had similar free CSF GABA concentrations. These results would not support the hypothesis that patients with epilepsy have a global disturbance of GABA function. CSF taurine, asparagine, aspartate, glycine and alanine were significantly reduced in patients with epilepsy compared to the control population.
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PMID:GABA and amino acid concentrations in lumbar CSF in patients with treated and untreated epilepsy. 350 8

The effects on hippocampal extra- and intracellular amino acids of focal injection of folic acid into the amygdala in the rabbit were studied with brain dialysis. Folate seizures were accompanied by pronounced elevations of extracellular alanine and phosphoethanolamine. The increase of extracellular alanine was related to an enhanced level of this amino acid in total hippocampal tissue, whereas phosphoethanolamine was unaltered in tissue biopsies. Folate seizures did not significantly affect extracellular aspartate and extracellular glutamate was only slightly elevated (50-75% over baseline values). The tissue concentration of glutamate remained at control levels during the seizures and tissue aspartate was decreased by 28%. Extracellular glutamine decreased rapidly after folate injection with a concomitant increase of total hippocampal glutamine. Neither extra- nor intracellular taurine was affected by folate epilepsy. The experiments also encompassed measurements of the extracellular purine catabolites inosine, hypoxanthine and xanthine. Folic acid-induced epilepsy produced changes in these compounds indicative of moderately accelerated degradation of adenosine 5'-triphosphate. The findings support the view of glutamate as a mediator of epilepsy-related brain damage. It is, however, questionable if the small enhancement of extracellular glutamate is enough to provoke neuronal necrosis associated with folate epilepsy.
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PMID:Alterations in hippocampal extracellular amino acids and purine catabolites during limbic seizures induced by folate injections into the rabbit amygdala. 367 May 97

The omega-phosphono-alpha-aminocarboxylic acids, e.g., 2-amino-5-phosphonopentanoate and 2-amino-7-phosphonoheptanoate, are known to act as potent and selective antagonists at N-methyl-D-aspartate receptors and to have a pronounced anticonvulsant action on a variety of animal models of epilepsy. In the present study, the effects of these omega-phosphono-alpha-aminocarboxylic acids on E1 mice were investigated. These mice are inbred mutant epileptic mice, which are highly susceptible to convulsive seizures upon throwing stimulation. 2-Amino-3-phosphonopropionate injected intraventricularly (at a dose of 1.04 mumol) had a marked anticonvulsant action, but at a lower dose (0.1 mumol), it induced running fits. 2-Amino-4-phosphonobutyrate induced transitory excitation just after the injection, followed by sedation. 2-Amino-5-phosphonopentanoate induced marked behavioral sedation. 2-Amino-6-phosphonohexanoate induced tonic-clonic convulsions and epileptic discharges in electroencephalograms. 2-Amino-7-phosphonoheptanoate showed a strong anticonvulsant action at a dose of 1.27 mumol, but it induced myoclonic seizures at a lower dose. Amino acid analyses of E1 mouse brain showed that 2-amino-3-phosphonopropionate increased the glutamine level, 2-amino-4-phosphonobutyrate decreased the aspartic acid level, 2-amino-5-phosphonopentanoate decreased the glutamic acid level, 2-amino-6-phosphonohexanoate decreased the glutamic acid, glutamine, gamma-aminobutyric acid, glycine and alanine levels, and 2-amino-7-phosphonoheptanoate decreased the glutamic acid label 1 hour after their injection. These findings suggest that the effects of omega-phosphono-alpha-aminocarboxylic acids on the E1 mouse brain are multiple and complicated, depending on the numbers of their carbon chain.
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PMID:The effect of omega-phosphono-alpha-aminocarboxylic acids on seizures and brain amino acid levels in E1 mice. 367 86


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