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

A study was performed to examine the specific binding of excitatory amino acid (EAA) receptor subtypes in 5 brain regions of rats kindled from the amygdala or hippocampus, using extensively washed and Triton X-100-treated membranes. Seven days after the last amygdala kindled seizure, [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10- imine maleate ([3H]MK-801) binding, which labels N-methyl-D-aspartate (NMDA)-sensitive receptor-linked cation channels, decreased significantly only in the amygdala of kindled rats compared to that of controls under equilibrium assay conditions. There was no significant change in [3H]MK-801 binding in the amygdala or hippocampus 7 days after the last hippocampal kindled seizure, or 28 days after the last amygdala kindled seizure. Nor was there a significant change in NMDA-sensitive [3H]glutamate, strychnine-insensitive [3H]glycine, [3H]spermidine, [3H]kainate or [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA) binding in any brain region 7 days after the last amygdala kindled seizure, or in the hippocampus 28 days after the last amygdala kindled seizure. These results indicate that [3H]MK-801 binding sites labeling NMDA-sensitive receptor-linked cation channels in the amygdala undergo downregulation only transiently, but that none of the subcomponents of the NMDA receptor macromolecular complex exhibit enduring changes at steady state following the completion of amygdala kindling.
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PMID:Ionotropic excitatory amino acid receptors in discrete brain regions of kindled rats. 132 75

A behavioural study of the domoic acid (DOM)-induced convulsive behaviour after intracerebroventricular administration was carried out in rats and mice. DOM-induced behaviours were compared to those elicited by other excitatory amino acid (EAA) agonists N-methyl-D-aspartate (NMDA), alpha-amino-3- hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainic acid (KA), in such a way as to assess the possible similarities between DOM-induced effects and EAA subtype receptor activation in vivo. In rat, DOM (0.03-3 nmol/rat) caused a complex pattern of convulsive behaviour, quantified by means of a 15-point rating scale. DOM-induced behavioural profile was characterized at the lower doses by "preconvulsive" behaviours as wet dog shakes, hypermotility, mild facial clonus. At higher doses, DOM caused clonic convulsions followed by the "status epilepticus" syndrome (wet dog shakes, forelimb clonus, rearing, salivation). Rats treated with KA (0.3-10 nmol/rat) showed an almost identical behavioural profile. AMPA (1-10 nmol/rat)-induced convulsive behaviour was similar to DOM and KA only at the higher doses. NMDA (0.25-10 nmol/rat) caused clonic convulsions but not "status epilepticus". In mice, similar results were obtained: all the tested drugs induced generalized seizures, but only animals treated with DOM, KA and AMPA showed a prolonged sequence of seizures with forelimb clonus. Our results confirm the findings reported in the literature and support the hypothesis that DOM and KA act at the same EAA receptor.
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PMID:Domoic acid toxicity in rats and mice after intracerebroventricular administration: comparison with excitatory amino acid agonists. 138 Jul 8

A case of propionic acidemia is reported. The main features of this patient were recurrent vomiting, ketosis and occasional episodes of seizure. Serum concentrations of propionic acid and glycine were within the normal range. Blood ammonia was slightly elevated. Characteristic organic acids were present in the patient's urine. they were: 3-hydroxypropionic acid, propionylglycine, methyl-citric acid, tiglyglycine, 3-hydroxyvaleric acid, etc. The etiology, pathogenesis, clinical features, diagnosis, and treatment of propionic acidemia are briefly discussed.
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PMID:[Propionic acidemia: one case report]. 183 12

Bilateral inferior olive lesions, produced by systemic administration of the neurotoxin 3-acetylpyridine (3AP) produce a proconvulsant state specific for strychnine-induced seizures and myoclonus. We have proposed that these phenomena are mediated through increased excitation of cerebellar Purkinje cells, through activation of glutamate receptors, in response to climbing fiber deafferentation. An increase in quisqualic acid (QA)-displaceable [3H]AMPA [(RS)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid] binding in cerebella from inferior olive-lesioned rats was observed, but no difference in [3H]AMPA binding displaced by glutamate, kainic acid (KA) or glutamate diethylester (GDEE) was seen. The excitatory amino acid antagonists GDEE and MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10 imine] were tested as anticonvulsants for strychnine-induced seizures in 3AP inferior olive-lesioned and control rats. Neither drug effected seizures in control rats, however, both GDEE and MK-801 produced a leftward shift in the strychnine-seizure dose-response curve in 3AP inferior olive-lesioned rats. GDEE also inhibited strychnine-induced myoclonus in the lesioned group, while MK-801 had no effect on myoclonus. The decreased threshold for strychnine-induced seizures and myoclonus in the 3AP-inferior olive-lesioned rats may be due to an increase in glutamate receptors as suggested by the [3H]AMPA binding data.
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PMID:The effects of inferior olive lesion on strychnine seizure. 212 20

This study reports the activity of a structurally novel excitatory amino acid receptor antagonist, LY233053 [cis-(+-)-4-[(2H-tetrazol-5-yl)methyl]piperidine-2-carboxylic acid], the first tetrazole-containing competitive N-methyl-D-aspartic acid (NMDA) antagonist. LY233053 potently inhibited NMDA receptor binding to rat brain membranes as shown by the in vitro displacement of [3H] CGS19755 (IC50 = 107 +/- 7 nM). No appreciable affinity in [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) or [3H]kainate binding assays was observed (IC50 values greater than 10,000 nM). In vitro NMDA receptor antagonist activity was further demonstrated by selective inhibition of NMDA-induced depolarization in cortical wedges (IC50 = 4.2 +/- 0.4 microM vs. 40 microM NMDA). LY233053 was effective after in vivo systemic administration in a number of animal models. In neonatal rats, LY233053 selectively blocked NMDA-induced convulsions (ED50 = 14.5 mg/kg i.p.) with a relatively short duration of action (2-4 hr). In pigeons, LY233053 potently antagonized (ED50 = 1.3 mg/kg i.m.) the behavioral suppressant effects of 10 mg/kg of NMDA. However, a dose of 160 mg/kg, i.m., was required to produce phencyclidine-like catalepsy in pigeons. In mice, LY233053 protected against maximal electroshock-induced seizures at lower doses (ED50 = 19.9 mg/kg i.p.) than those that impaired horizontal screen performance (ED50 = 40.9 mg/kg i.p.). Cholinergic and GABAergic neuronal degenerations after striatal infusion of NMDA were prevented by single or multiple i.p. doses of LY233053. In summary, the antagonist activity of LY233053 after systemic administration demonstrates potential therapeutic value in conditions of neuronal cell loss due to NMDA receptor excitotoxicity. The relatively short duration of action of LY233053 may make this compound particularly advantageous as a neuroprotective agent in the treatment of acute conditions such as cerebral ischemia.
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PMID:Pharmacological characterization of LY233053: a structurally novel tetrazole-substituted competitive N-methyl-D-aspartic acid antagonist with a short duration of action. 214 88

Nonsalicylate, nonsteroidal anti-inflammatory drugs (NSAIDs) can be divided into 4 chemical classes: acetic acids, fenamic acids, oxicams and propionic acids. Most NSAID overdoses result in a benign outcome. Of 50,614 exposures reported to poison centres in the United States in a 2-year period, 131 (0.26%) had a major outcome, with 10 deaths. Despite the generally mild effects reported in large patient series, isolated case reports have documented serious toxicity, such as seizures, hypotension, apnoea, coma and renal failure. The majority of these consequences occur after ingestion of substantial quantities by adults attempting suicide. Rarely, with ibuprofen and piroxicam, children who ingest small amounts in accidental exposure develop serious toxicity. Typical signs and symptoms of NSAID overdose include nausea, vomiting, headache, drowsiness, blurred vision and dizziness. Seizures are rarely documented across all NSAID classes, with the exception of mefenamic acid (where seizures occur in over one-third of cases), or following massive ingestion of other agents. Drugs in the propionic acid group have produced metabolic acidosis, respiratory depression and coma in severe cases. Ibuprofen is the agent with the most published data on overdose, probably because it is available without a prescription in many countries. Symptoms are unlikely after ingestion of 100 mg/kg or less, and are usually not life-threatening unless more than 400 mg/kg is ingested. There is some relationship between plasma concentrations and the potential for development of symptoms, but plasma concentrations have no impact on treatment decisions. Treatment of NSAID overdose is entirely supportive. Recent trends in emergency department procedures regarding gastric decontamination are evolving towards the recommended administration of activated charcoal without gastric emptying in patients presenting more than 1 hour after ingestion, although gastric lavage, followed by administration of activated charcoal, may be advisable in patients who present earlier. Home administration of syrup of ipecac is still recommended if treatment is given shortly after ingestion, with a few exceptions: for example, ipecac is contraindicated after ingestion of mefenamic acid or ibuprofen in amounts greater than 400 mg/kg. Urine alkalinisation and diuresis have been recommended to enhance the elimination of NSAIDs, based on a pKa in the range of 3 to 5. However, because the drugs are universally highly protein bound, with little unchanged renal excretion, this technique is not likely to be beneficial. Haemodialysis is also unlikely to enhance elimination, but may be required if oliguric renal failure develops. Multiple dose activated charcoal may be useful in enhancing elimination of NSAIDs with long half-lives, such as piroxicam and sulindac.
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PMID:Toxic effects of nonsteroidal anti-inflammatory drugs in overdose. An overview of recent evidence on clinical effects and dose-response relationships. 219 51

A 10-month-old girl with mild developmental delay became hemiplegic after seizures. Cranial CT scan and magnetic resonance imaging (MRI) revealed no lesions related to vascular diseases, but brain atrophy on the right side was remarkable. Digital subtraction angiography showed slightly decreased visualization of peripheral branches of the right medial cerebral artery. Propionic acidaemia was diagnosed on the basis of high plasma levels of propionic acid and its metabolites and the elevated urinary excretion of these acids. With therapy, the levels of these acids fell, and her left hemiplegia disappeared 3 months later.
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PMID:Acute infantile hemiplegia in a patient with propionic acidaemia. 237 22

The novel compound 2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid (NPC 12626) was evaluated for activity in a variety of tests associated with receptors for excitatory amino acids. NPC 12626 failed to inhibit the specific binding of RS-[3H] amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid or [3H] kainic acid to brain membranes in vitro but displaced both agonist and antagonist binding to N-methyl-D-aspartic acid (NMDA) receptors. Like cis-(+/-)-3-(2-carboxypiperazine-4-yl)propyl-1-phosphonic acid, NPC 12626 competitively blocked NMDA-induced enhancement of [3H]-1-thienylcyclohexyl)piperidine binding. In the voltage-clamped frog oocyte expression system, NPC 12626 was a competitive inhibitor of NMDA-evoked inward current with a pA2 of 6.24. After both i.c.v. or i.p. administration, NPC 12626 was a potent anticonvulsant in the pentylenetetrazol, maximal electroshock and NMDA seizure models. Furthermore, low doses (25 mg/kg) of NPC 12626 given i.v. were effective in preventing damage to the CA1 region of hippocampus in the gerbil model of global ischemia. Unlike the noncompetitive NMDA antagonist, phencyclidine, but like cis-(+/-)-3-(2-carboxypiperazine-4-yl)propyl-1-phosphonic acid and pentobarbital, NPC 12626 only partially substituted for phencyclidine in a drug discrimination study. The results of the current study indicate that NPC 12626 is a novel, systemically active and competitive NMDA receptor antagonist.
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PMID:Pharmacological profile of NPC 12626, a novel, competitive N-methyl-D-aspartate receptor antagonist. 254 56

Naproxen, a nonsteroidal anti-inflammatory drug (NSAID), is a propionic acid derivative that possesses analgesic and antipyretic properties through inhibition of prostaglandin synthesis. The propionic acids have been considered the least toxic of the NSAIDs, and one, ibuprofen, is currently available as an over-the-counter medication. Though acidosis has been reported with ibuprofen, no such occurrence has been reported for naproxen sodium. We report the case of a 15-year-old girl who presented with severe metabolic acidosis and seizures that rapidly followed naproxen sodium ingestion. Serum bicarbonate levels returned to normal 12 hours after admission and correlated with the known pharmacokinetics of naproxen. The pharmacokinetics of naproxen and treatment of its overdose, and possible mechanisms of metabolic acidosis are reviewed.
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PMID:Severe metabolic acidosis after acute naproxen sodium ingestion. 255 70

All excitatory amino acid antagonists studied: diethyl esters of aspartic (DEEA) and glutamic (DEEG) acids, 2-amino-3-phosphono-propionic acid (APPA) and 2-amino-4-phosphono-butanoic acid (APBA), diminished the amplitude of excitatory postsynaptic potentials (EPP) of the locust (Locusta migratoria migratorioides) muscle fibers and arbitrary blocked glutamate (GLU) and aspartate (ASP) responses. Kynurenine (KYN) and quinolinic (QUI) acid had no effect on EPP even at a concentration of 2 X 10(-2) M. The antagonists were not strictly selective against intracerebroventricularly administered endogenous convulsants: GLU, ASP, KYN and QUI and in simulation of experimental seizures in mice. The antagonists structurally similar to ASP prevented ASP- and KYN-induced seizures in lower doses than GLU derivatives. Anti-KYN, but not anti-QUI DEEA, DEEG, APPA and APBA efficacy suggests that KYN and QUI act on different structures or binding sites.
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PMID:[Effect of excitant amino acid antagonists on glutamate receptors in the locust and on convulsions induced by glutamate, aspartate, kynurenine and quinolinic acid in mice]. 286 99


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