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

The audiogenic seizure-inducing drug H13/04 was found to elicit opposing effects on the in vivo accumulation of 5-HTP (5-hydroxytryptophan) and DOPA (3,4-dihydroxyphenylalanine) in the brain following inhibition of L-amino acid decarboxylase. In strains of mice that normally do not exhibit audiogenic seizures, H13/04 retarded the accumulation of 5-HTP in the telencephalon, diencephalon and brainstem and enhanced the accumulation DOPA in the diencephalon and brainstem. The duration of the biochemical action of H13/04-correlated with the duration of the behavioral effect. When H13/04 is administered to strains of mice with a genetically-determined susceptibility to audiogenic seizures, but at an age when they are developing resistance to seizures, H13/04 does not alter the incidence of sound-induced seizures. The effect on the accumulation of 5-HTP and DOPA was similar to that noted in the genetically-resistant strain; a retardation of the accumulation of 5-HTP in the telencephalon and brainstem and an enhancement of DOPA accumulation in the brainstem. Since the rate of accumulation of 5-HTP and DOPA is a measure of the in vivo rates of tryptophan and tyrosine hydroxylase, respectively, the results may reflect changes in neural activity with consequent effects on the synthesizing enzymes. These results emphasize the usefulness of the drug in analyzing central mechanisms underlying audiogenic seizure activity and in studying functional properties and interactions of the central catechol-and indoleamine systems.
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PMID:Central action of a catechol-amide seizure-inducing agent: opposing effect on tyrosine and tryptophan hydroxylase activity in vivo. 0 34

Adult C57BL/10Bg mice, normally resistant to audiogenic seizures, became susceptible when the mothers drank 10 per cent ethanol in water during pregnancy and for 14 days postpartem. Reserpine enhanced the incidence of seizures, and the effect was reversed by 5-hydroxytryptophan but not by dihydroxyphenylalanine. p-Chlorophenylalanine also enhanced the incidence of seizures, whereas alpha-methyl equals p equals tyrosine did not effect. Monsodium glutamate almost completely prevented seizures. These results are consistent with the interpretation that the serotonergic systems may be among those involved in the seizure mechanism induced by fetal and early exposure to ethanol.
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PMID:Effects of aminergic drugs and glutamic acid on audiogenic seizures induced by early exposure to ethanol. 12 3

Brain serotonin levels and susceptibility to audiogenic seizures were examined in a strain of inbred audiosusceptible mice and in control mice at intervals from two hours to one week after treatment with several agents known to modify serotonin metabolism. Although p-chlorophenylalanine produced a gradual decrease in brain serotonin there appeared to be no temporal correlation between this effect and the rapid reduction in seizure susceptibility. 5-Hydroxytryptophan and tranylcypromine led to significant increases in serotonin, but only the former caused a proportinal reduction in seizure activity. Reserpine and alpha-propyldopacetamide decreased serotonin levels but only reserpine caused an intensification of seizure activity proportional to serotonin changes. On the basis of our data, effects of 5-hydroxytryptophan and reserpine on seizure susceptibility appear to be linked to observed brain serotonin levels; further studies are needed to elucidate the mode of action of p-chlorophenylalanine.
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PMID:Audiogenic seizures in mice: influence of agents affecting brain serotonin. 13 36

Convulsive responsiveness of O'Grady mice, inbred for susceptibility to audiogenic seizures, was decreased following treatment with the serotonin precursor, 5-hydroxytryptophan, or serotonin depletor, p-chlorophenylalanine. Neither agent exerted any antagonistic or synergistic action on the effect of the other. Upon sequential administration, their effects were additive. There was no indication that the increase in brain serotonin due to administration of its direct precursor interfered with the protective effect of p-chlorophenylalanine against seizures. Neither was there evidence that p-chlorophenylalanine-induced interruption of biosynthesis which led to severe depletion of brain serotonin affected the protective action of 5-hydroxytryptophan.
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PMID:Additive effect of 5-hydroxytryptophan and p-chloro-phenylalanine in preventing audiogenic seizures in inbred mice. 14 Apr 18

5-Hydroxytryptophan (5-HTP) reduced the intensity of both audiogenic and pentylenetrazol seizures. p-Chlorophenylalanine reduced audiogenic seizure (AGS) susceptibility but failed to change the pentylenetetrazol seizure (PTS). Drugs blocking brain serotonin (5-HT) receptors suppressed AGS but caused no clear effects upon PTS. Pentylenetetraziol-induced shock increased brain 5-hydroxyindoleacetic acid (5hiaa) concentrations and decreased 5-HT levels. Single audiogenic shock decreased the acumulation of 5-HT and 5-HIAA in the brains of mice pretreated with 5-HTP. On the other hand PTS increased the accumulation of 5-HT and 5-HIAA in the brains of mice pretreated with 5-HTP. It is suggested that AGS decrease brain 5-HT turnover whilst PTS cause an opposite effect.
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PMID:Brain serotonin and epileptic seizures in mice: a pharmacological and biochemical study. 14 40

Modification of electroshock (60 Hz; a.c.) convulsive responses and thresholds by monoamine-reducing drugs was investigated in developing rats. Throughout postnatal development, tetrabenazine (TBZ) reduced brain monoamines and increased the severity of motor responses to electroshock. The predominant maximal response in control pups progressed from hyperkinesia (day 1) to clonic convulsions (day 3) and tonic forelimb (day 7) and hindlimb (day 19) extension. The pattern in TBZ-treated pups progressed from tonic forelimb extension (day 1) to tonic hindlimb extension (day 7). On day 7, TBZ reduced the thresholds for clonic (CT) and tonic convulsions (TT) to 41 and 24% of control, respectively. Reserpine (1.25 mg/kg, 24 hours) decreased the TT but not the CT; TBZ, 4 hours before reserpine, prevented this decrease. A higher dose of reserpine (2.5 mg/kg) decreased both the CT and TT. On day 8, TBZ (25 mg/kg, 4 hours) decreased the TT (46% control); L-dihydroxyphenylalanine, but not 5-hydroxytryptophan prevented this decrease. Intracisternal 6-hydroxydopamine reduced the TT on day 8, while intracisternal 5,7-dihydroxytryptamine had no effect despite a 46% reduction in serotonin. The results indicate that in the neonatal rat brain, monoaminergic systems are sufficiently mature to attenuate electroshock convulsive responses, perhaps by limiting propagation of seizure discharge.
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PMID:Modification of electroshock convulsive responses and thresholds in neonatal rats after brain monoamine reduction. 30 60

Brain levels of tyrosine, dopamine (DA), noradrenaline (NA), tryptophan, 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were measured after 30, 60 and 120 min of sustained seizure activity, induced in paralyzed, artificially ventilated and anaesthetized (70% N2O) rats by administration of bicuculline (1.2 mg/kg i.v.). In separate animals the rates of accumulation of DOPA and 5-hydroxytryptophan (5-HTP) were estimated in three different brain regions after blockage of the aromatic L-amino acid decarboxylase with NSD 1015 (100 mg/kg). The tissue level of NA was markedly reduced at 30 min and remained low during 120 min of sustained epileptic seizures. In contrast, the DA concentration, being essentially unaffected at 30 min, continuously increased during the following 90 min. 5-HT decreased significantly after 30 min but returned to control levels following 60 and 120 min of seizure activity. The 5-HIAA concentration progressively increased. In all three brain regions (striatum, limbic forebrain and hemispheres) the rate of tyrosine hydroxylation increased. Tryptophan hydroxylation showed a significant increase only in the limbic forebrain. The results suggest that bicuculline-induced seizures lead to an increased functional activity in NA neurons and, at least initially, also in 5-HT neurons. In contrast, DA neurons appear to be inhibited.
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PMID:Monoamine metabolism during bicuculline-induced epileptic seizures in the rat. 30 80

A deficiency of hepatic dihydropteridine reductase (DHPR) activity was found in a neurologically impaired infant with mild hyperphenylalaninemia and normal levels of hepatic phenylalanine hydroxylase. DHPR is required for the regeneration of tetrahydrobiopterin, an essential cofactor in aromatic amino acid hydroxylation, a necessary step in the biosynthesis of the neurotransmitters, dopamine and serotonin. Evidence for decreased synthesis of these transmitters in this patient was provided by the finding of reduced levels of homovanillic acid and 5-hydroxyindole acetic acid, metabolites of dopamine and serotonin, respectively, in the cerebrospinal fluid and urine. Treatment with dopamine and serotonin precursors, L-3,4 dihydroxyphenylalanine and 5-hydroxytryptophan, respectively, was associated with improvement in temperament and motor tone and less frequent seizures. However, there was no improvement in gross motor function or language development.
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PMID:Dihydropteridine reductase deficiency associated with severe neurologic disease and mild hyperphenylalaninemia. 31 82

Electrolytic lesions of the median raphe nucleus and substantia nigra markedly increased susceptibility to pentetrazole seizures in rats. L-5-hydroxytryptophan, considerably increasing the serotonin (5-HT) level in the brain, markedly inhibited the seizures and abolished the seizure-enhanced effect of lesion of the substantia nigra. L-DOPA tended to potentiate the seizures-enhancing effect produced by lesions of the median raphe nucleus. The changes in the brain 5-HT level and the intensity of pentetrazole seizures were correlated. The results indicate that the balance between neurotransmitter systems in the brain is of importance to the susceptibility to pentetrazole convulsions.
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PMID:The effect of L-DOPA and L-5-hydroxytryptophan on the pentetrazole seizures in rats after lesions of the median raphe nucleus and substantia nigra. 31 24

Laboratroy and clinical evidence indicates that tricyclic antidepressants lower seizure threshold and in high doses may induce generalised seizures. In baboons with photosensitive epilepsy (Papio papio) the effects of 2 tricyclic antidepressants (imipramine and chlorimipramine) and of maprotiline and Nomi fensine have been studied (i.v. dose range 1-20 mg/kg. Imipramine, chlorimipramine and maprotiline (10 mg/kg i.v.) lowered seizure threshold to a comparable extent, whereas Nomifensine (10 mg/kg i.v-) did not enhance myoclinic responses to photic stimulation. Generalised seizures were seen 15-30 min after imipramine or chlorimipramine (20 mg/kg), and these two drugs showed no difference in their epileptogenicity. Administration of 5-hydroxytryptophan (25 mg/kg i.v.) 90 min before chlorimipramine or imipramine (10 mg/kg) completely blocked the usual augmentation of photically-induced epileptic responses. It is concluded that enhancement of serotoninergic activity following blockade of 5-HT re-uptake within the brain is unlikely to be responsible for enhanced myoclonic responses and epileptogenic seizures seen after tricyclic antidepressants. Nomifensine is significantly less epileptogenic than imipramine or chlorimipramine.
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PMID:Seizure activity in photosensitive baboons following antidepressant drugs and the role of serotoninergic mechanisms. 40 67


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