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

An association has recently been proposed between the incidence of seizures and prolonged consumption of the phenylalanine-containing artificial sweetener, aspartame. Since consumption of aspartame, unlike dietary protein, can elevate phenylalanine in brain, and thereby inhibit the synthesis and release of neurotransmitters known to protect against seizure activity, the effect of oral doses of aspartame on the sensitivity of mice to the proconvulsant agents, pentylenetetrazole and fluorothyl was studied. Doses of aspartame were used which increased phenylalanine more than tyrosine in brain, as occurs in humans after the consumption of any dose of aspartame. Pretreatment with aspartame significantly increased the percentage of animals convulsing after administration of pentylenetetrazole and significantly lowered the CD50 for this convulsant. The average time to onset of seizures induced by fluorothyl in control mice was 510 sec; pretreatment with oral doses of 1000, 1500 and 2000 mg/kg of aspartame 1 hr earlier significantly reduced the time required to elicit seizures (394, 381 and 339 sec, respectively). The seizure-promoting effect of aspartame could be demonstrated 30, 60 or 120 min after the 1000 mg/kg dose. The seizures induced by either convulsant were potentiated by equimolar amounts of phenylalanine, a major endogenous metabolite of aspartame, while the other metabolites, aspartic acid and methanol, were without effect. Administration together with aspartame of the large neutral amino acid valine, which competes with phenylalanine for entry into the brain, completely abolished the seizure-promoting effect of aspartame.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Administration of aspartame potentiates pentylenetetrazole- and fluorothyl-induced seizures in mice. 335 66

The alpha- and beta-stereoisomers of kainate correspond sterically to the L- and D-isomers of glutamate. Alpha-Kainate is a potent excitant at a specific membrane receptor site (kainate receptor). Beta-Kainate has been proposed as a functional N-methyl-D-aspartate antagonist in vivo. Because of the structural similarities between the alpha- and beta-stereoisomers of kainate we have investigated the interactions of both compounds with N-methyl-D-aspartate-mediated excitation in two well established animal models for assessing the action of excitatory amino acids and their antagonists in vivo: determination of CD50 (convulsant dose) for myoclonic seizures in mice and electromyographic measurement of muscle tone in genetically spastic rats. We find that alpha-kainate and beta-kainate produce myoclonic seizures in mice when given intracerebroventricularly and increase the muscle tone in genetically spastic rats when given intrathecally. Alpha-Kainate is about 5000 times more potent than beta-kainate as a convulsant and about 1000 times more active than beta-kainate in increasing the muscle tone. The excitatory actions of alpha-kainate and of beta-kainate are blocked by gamma-D-glutamylaminomethylsulphonate, a preferential kainate/quisqualate antagonist, but not by (+/-)-2-amino-7-phosphonoheptanoate, a specific N-methyl-D-aspartate antagonist. Surprisingly, alpha-kainate and beta-kainate antagonize the myoclonic seizures and the increase in muscle tone produced by N-methyl-D-aspartate, and potentiate both the anticonvulsant and myorelaxant actions of (+/-)2-amino-7-phosphonoheptanoate. Quisqualate induces myoclonic seizures in mice after intracerebroventricular application and increases muscle tone in genetically spastic rats following intrathecal injection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Unusual interactions of excitatory amino acid receptor agonists: alpha- and beta-kainate antagonize motor responses to N-methyl-D-aspartate in rodents. 355 May 20

Several lines of evidence suggest that the convulsant actions of caffeine are mediated through benzodiazepine receptors. A pharmacogenetic approach has been used to further explore the relationship of these receptors to caffeine-induced seizures. The susceptibility of two inbred strains of mice (CBA and SWR) to the convulsant actions of picrotoxinin, strychnine, Ro 5-4864 and DMCM was examined. Previous studies have demonstrated these two strains differ in their susceptibilities to the convulsant action of caffeine. While no differences were observed between these two strains in susceptibility to tonic seizures induced by picrotoxinin, RO 5-4864 or strychnine, SWR mice were significantly less sensitive to tonic seizures induced by DMCM compared to CBA mice (CD50 values in CBA and SWR mice were 6 and 12 mg/kg IP). Both clonazepam and the benzodiazepine receptor antagonist, Ro 15-1788, significantly blocked caffeine-induced seizures. Further, when subconvulsant doses of caffeine and DMCM were combined, a synergistic action was observed. Taken together, these findings support the hypothesis that the convulsant actions of caffeine result from an action at benzodiazepine receptors, and that the hyporesponsiveness of the SWR strain to both caffeine- and DMCM-induced seizures could result from an inherited abnormality in these sites.
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PMID:Coincidence of seizure susceptibility to caffeine and to the benzodiazepine inverse agonist, DMCM, in SWR and CBA inbred mice. 357 58

A new animal model for epilepsy was successfully produced by microinjection of cobaltous chloride into the lateral cerebral ventricle of the rat. The median convulsive dose (CD50) and the median lethal dose (LD50) of CoCl2 was 0.45 microM/10 microliters (0.27-0.77 microM/10 microliters) and 1.07 microM/10 microliters (0.73-1.57 microM/10 microliters), respectively. The behavioral changes, electrocorticogram (ECoG), and the action of 5 classical anticonvulsants were studied using this new model. Seizures induced by cobaltous chloride are clinically similar to those produced by systemic administration of kainic acid and amygdala kindling. These are characterized by staring spells, wet dog shakes, mild convulsive movements, and stereotyped convulsions. ECoG findings demonstrated a unique epileptic burst during the wet dog shakes. Generalized epileptiform discharges were seen during typical seizures. The burst of spikes first occurred in the opposite temporal and frontal regions; and then became generalized. Among the 5 anticonvulsants studied, phenobarbital (30 mg/kg) and nitrazepam (3 mg/kg) completely antagonized the seizures; carbamazepine showed a moderate effect; and phenytoin as well as sodium valproate showed little effect. It is postulated that the seizures induced by cobaltous chloride may originate in the limbic system; and that cobalt ions are responsible for the seizure-inducing action. The mechanism remains to be investigated.
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PMID:Seizures induced by intraventricular microinjection of ionized cobalt in the rat--a new experimental model of epilepsy. 404 34

Ro 5-4864 (4'-chlorodiazepam) elicited convulsions in mice with a CD50 of 23.5 mg/kg (i.p.) and increased the firing rate of substantia nigra zona reticulata neurons in a dose dependent fashion (0.5-4 mg/kg i.v.). Diazepam and clonazepam, but not Ro 15-1788, were potent inhibitors of Ro 5-4864 induced convulsions. Ro 15-1788 was also ineffective in reversing Ro 5-4864 induced increases in cell firing of zone reticulata neurons. Muscimol potently inhibited the seizures and reversed increases in cell firing elicited by Ro 5-4864. Phenobarbital and pentobarbital inhibited Ro 5-4864 induced convulsions with moderate potencies, while phenytoin and carbamazepine were ineffective at doses of up to 100 mg/kg. These observations suggest that Ro 5-4864 does not elicit its pharmacologic actions through a direct action at a 'brain-type' benzodiazepine receptor. However, both the profile and potency of compounds effective in inhibiting the electrophysiological and pharmacological effects of Ro 5-4864 suggest that this compound may act by perturbation of a component of the GABA-benzodiazepine receptor chloride ionophore complex. These findings do not, however, rule out a direct involvement of the high affinity 'peripheral-type' benzodiazepine receptors found in brain.
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PMID:Electrophysiological and pharmacological actions of the convulsant benzodiazepine Ro 5-4864. 632 93

Lidocaine and procaine seizure thresholds were studied. The i.p. median convulsant dose (CD50) of lidocaine and procaine with saline pre-treatment was 95 and 240 mg/kg, respectively. Dopamine depletion by pre-treatment with d1-alpha-methyl-p-tyrosine plus dihydroxyphenylserine resulted in a significant drop of CD50 to 69 and 175 mg/kg for lidocaine and procaine, respectively. Serotonin depletion by pre-treatment with p-chlorophenylalanine resulted in a significant drop of CD50 to 68 mg/kg for lidocaine, but no significant change for procaine.
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PMID:Alteration of lidocaine- or procaine-induced convulsions by manipulation of brain amines. 645 Jul 81

The effects of postweaning housing in environmental complexity (EC) or isolation cage (IC) conditions upon the development of anesthesia following sodium pentobarbital administration and upon seizure susceptibility following metrazol administration were studied in separate groups of rats. Male and female EC rats lost the righting reflex and developed unconsciousness more rapidly following sodium pentobarbital injection (105 mg/kg, IP) than did littermate IC rats. Male EC and IC rats did not differ in the CD50 (50% convulsion dosage by log probit analysis) following injection of a range of metrazol doses (20 to 35 mg/kg, IP) when they were kept in a quiet dimly lighted room. However, the addition of stroboscopic light stimulation (1-100 Hz) to the above procedure (doses 17.5 to 30 mg/kg) reduced the CD50 for the IC rats but did not affect the CD50 for the EC rats. The results support the view that brain excitability is lower in animals reared in environments providing higher levels of sensory stimulation.
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PMID:Differential rearing affects responsiveness of rats to depressant and convulsant drugs. 666 59

It has been demonstrated in experiments on F1 (CBA X C57BL/6) hybrid mice and random-bred white mice that daily administration of corazol (30 mg/kg) led to the development of pharmacological kindling. The kindling was marked by a statistically significant reduction in the convulsant dose (CD50) of corazol, picrotoxin, bicuculline and thiosemicarbazide. No substantial differences were discovered in the degree of seizures induced by strychnine in the "kindling" and control groups. It is assumed that the mechanisms of the corazol kindling are effected via impairment of the GABA-benzodiazepine receptor complex.
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PMID:[Changes in the convulsant readiness of mice as affected by korazol]. 671 97

Median convulsant (CD50) and median lethal (LD50) doses of three representative local anesthetics were determined in adult mice to evaluate the threat to life of local anesthetic-induced convulsions. The CD50 and LD50, respectively, were 57.7 and 58.7 mg/kg for bupivacaine, 111.0 and 133.1 mg/kg for lidocaine, and 243.4 and 266.5 mg/kg for chloroprocaine. When given intraperitoneally, bupivacaine thus was only about twice as toxic as lidocaine and four times as toxic as chloroprocaine. Convulsions always preceded death, except after precipitous cardiopulmonary arrest from extreme doses. A CD50 dose of local anesthetic (causing convulsions in 50% of mice) was fatal in 90% of bupivacaine-induced seizures, in 57% of the chloroprocaine group, and in 6% of the lidocaine group. The narrow gap between convulsant and lethal doses of local anesthetics indicates that untreated convulsions present much more of a threat to life than heretofore appreciated.
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PMID:Deaths from local anesthetic-induced convulsions in mice. 718 75

The effect of L-arginine (L-Arg), D-arginine (D-Arg), N-nitro-L-arginine methyl ester (L-NAME) and N-monomethyl-L-arginine (L-NMMA) on the kainate-induced seizures was studied in mice. It was found that the precursor of nitric oxide (NO) L-Arg (150-600 mg/kg i.p.) increased dose-dependently the dose of kinate necessary to produce clonic convulsions in 50% of the animals (CD50). Such an anticonvulsant effect was not observed in mice pretreated with D-Arg (150-600 mg/kg i.p.), the latter drug not being a substrate for NO formation. The inhibitors of NO synthase L-NAME and L-NMMA, both administered in doses of 30-30 mg/kg i.p., reduced the convulsive threshold by decreasing the CD50 of kainate. Moreover, L-NAME (3 mg/kg) antagonized the anticonvulsant effect of L-Arg (300 mg/kg). These results indicate that NO may play a role of an endogenous anticonvulsant substance in mice.
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PMID:The role of nitric oxide in the kainate-induced seizures in mice. 751 94


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