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)

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

Our group has been carrying out interdisciplinary studies on the effects of prenatal and postnatal protein malnutrition on the developing rat brain. Anatomical, physiological, biochemical and behavioral approaches using the same animal model have revealed that protein malnutrition affects the brain at various levels, i.e., (1) anatomical, as revealed by Golgi findings of deranged dendritic trees on analysis of cortical and subcortical areas; (2) physiological, as revealed by delayed sleep pattern maturation, disturbances in seizure thresholds, slowing of sensory cortico-cortical and thalamocortical evoked potentials, and changed power in hippocampal theta activity; (3) biochemical, as revealed by marked increases in biogenic amines dating from birth, as well as modifications in tryptophan metabolism; and (4) behavioral, as revealed by various changes in responses to different kinds of aversive stimulation. Reversal studies have revealed that many changes are permanent and not amenable to nutritional rehabilitation even at birth, which is before the brain growth spurt in the rat. Our paradigm closely mimicks the human condition of low level, chronic protein undernutrition and thus reveals the underlying disturbances due to malnutrition. The dietary reversal studies are attempts at pin-pointing critical brain growth periods, beyond which recovery of functions is not possible.
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PMID:Developmental protein malnutrition: influences on the central nervous system of the rat. 4 55

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

Serum levels of total L-tryptophan (L-TP) were determined before and during treatment in patients suffering from endogenous depression, who were treated with L-TP, 6 g daily, and unilateral electroconvulsive therapy (ECT). The gaussian curve of initial L-TP concentrations changed into a bimodal distribution during treatment. The patients with initially lower L-TP levels also had lower L-TP levels during the treatment, thus forming the low-concentration group within the bimodal distribution. In the patients with higher initial concentrations, the L-TP levels increased to a much greater degree, forming the high-concentration group. Patients in this group needed a larger number of ECT's, probably owing to L-TP's property of shortening the seizure duration. No other background data or clinical variables showed significant differences between the groups. It is suggested that the bimodality of L-TP levels is genetically determined.
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PMID:Bimodal distribution of serum trypotphan level. 47 70

The effects of L-DOPA, L-tryptophan, monoamine oxidase inhibitor (MAOI), and MAOI plus L-tryptophan, each for 3 months, have been assessed in 10 severe, adult epileptics with placebo control. There was no overall reduction in seizure frequency, but 2 patients with minor partial seizures improved, 1 with L-DOPA, MAOI, and MAOI plus L-tryptophan, and the other with L-tryptophan and MAOI plus L-tryptophan. We have not been able to demonstrate an increased turnover of cerebral serotonin (5-HT), as measured by cerebrospinal fluid 5-hydroxyindoleacetic acid, after treatment with L-tryptophan for 3 months. This observation casts doubt on the ability of L-tryptophan to alter the long-term metabolism and functional activity of brain 5-HT. The importance of further exploration of manipulation of cerebral monoamines as a possible approach to the treatment of epilepsy is emphasized.
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PMID:Manipulation of cerebral monoamines in the treatment of human epilepsy: a pilot study. 62 66

The latency to tail-flick response in the rat was significantly prolonged by cerebroventricular infusion of 1.0 microgram of somatostatin (SRIF) and more so with 10.0 microgram. The D-tryptophan analog was less effective than native SRIF. Pretreatment with naloxone eliminated analgesia but not seizures induced by SRIF. Recording of the EEG activity enabled determination of the specific state of the sleep-waking cycle in which the repeated tail-flick responses were tested: latency was generally longer in both control and test animals when tail immersion was performed during the state of sleep or drowsiness rather than during the awake state. Although animals receiving SRIF were less likely to fall asleep between subsequent test trails, the average latency was actually longer than after control saline infusion when the animals slept more. SRIF, unlike other releasing factors and peptides tested, showed significant activity in an opiate radioreceptor assay. The blockade of SRIF action by naloxone pretreatment, along with binding of SRIF to opiate receptors in vitro, suggest opiate receptors to be involved in the mediation of analgesia observed in present study.
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PMID:Opiate-like naloxone-reversible actions of somatostatin given intracerebrally. 63 75

Each of six kynurenines tested (DL-kynurenine, quinolinic, 3-hydroxy-anthranilic, xanthurenic, picolinic, and nicotinic acids) injected into brain ventricles in mice in doses of 25--60 mcg produced motor excitement and/or clonic convulsions. Anthranilic acid did not produce these effects. The strongest metabolite was quinolinic acid, which was active in a dose of 1 mcg. It was also the only compound which produced motor excitement and convulsions after intraperitoneal injection (in doses of 400--600 mg/kg, i.e. 10,000--15,000 mcg per mouse). The hypothermic effect of intraventricularly-injected kynurenines was roughly similar to that of intraperitoneally-injected material at 100--1000 times higher doses. These data suggest poor penetration of kynurenines formed in the liver into the brain, and the possible involvement of these metabolites of tryptophan (particularly if they are formed inside the brain) in the mechanism of seizures.
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PMID:Stimulant and convulsive effects of kynurenines injected into brain ventricles in mice. 64 43

In an an intra-individual crossover trial depressed patients were treated with the 5-hydroxytryptamine (5-HT) precursor L-tryptophan (L-TP) and unilateral ECT, or with unilateral ECT alone. The oral dose of L-TP was 6 g the day before ECT and 3 g on the day of ECT, 4 hours before the treatment. The seizure duration was measured on EEG records. The time of the electrical stimulation needed to induce generalized seizures was similar for both treatment alternatives. Thus L-TP seems not to elevate the threshold to ECT-induced convulsions. The mean duration of a seizure was significantly shorter when the patients were treated with L-TP + ECT than when treated with ECT alone. It is suggested that L-TP exerts an inhibitory influence on the ability to sustain epileptic activity.
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PMID:Has tryptophan any anticonvulsive effect? 64 14

The role of biogenic amines in the proclivity of the baboon, Papio papio, to exhibit an epileptoid response to flashing light was studied. Intraventricular injections of epinephrine and norepinephrine reduced or blocked the photomyoclonic syndrome without modifying ongoing behavior. Epinephrine was effective at doses of 100 mg and more, and norepinephrine was effective at doses of 250 mg and more. Neither intraventricular injections of as much as 1.5 mg of dopamine and 1.0 mg of serotonin nor chronic systemic administration of L-dopa and L-tryptophan affected the syndrome, but reserpine, administered chronically at doses of 0.5 and 1.0 mg/kg/day, induced photosensitivity in previously nonphotosensitive animals. Seizure testing of usually photosensitive animals 12 hours after reserpine, 0.5 mg/kg, showed that the drug prevented totally or reduced the intensity of seizures in these animals. Studies of the spontaneous electroencephalogram and of visually evoked potentials of the reserpine-treated animals revealed changes in power spectra and in the averaged evoked response from the occipital area which paralleled the induction of photosensitivity. The probability that epinephrine and norepinephrine brain concentrations are essential for inhibitory modulation and control of seizures in this species is discussed.
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PMID:Biogenic amines and the photomyoclonic syndrome in the baboon, Papio papio. 81 81

Tyrosine, tryptophan, and their metabolites in the brain of ddY, non-stimulated El (El (-)), and stimulated El (El (+)) mice were measured using the three dimensional HPLC. The tryptophan content was lower in El (+) than ddY and El (-) mice. The 5-hydroxytryptophan content was much higher in both El groups. The serotonin content of El (+) was higher than that of ddY and El (-) mice. The kynurenine content was remarkably high in the El mice. The dopamine content was lower in El (-) than in ddY mice, whereas it was greater in El (+) than in El (-) mice. The norepinephrine showed higher levels in El (+) mice. These facts suggest that El mice possess congenital metabolic abnormalities of tryptophan and tyrosine and that kynurenine may play an important role as convulsant in El mice seizures along with changes in serotonin, dopamine, and norepinephrine that are inhibitory agents and responded to the repetitive convulsions.
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PMID:Regional distribution of tyrosine, tryptophan, and their metabolites in the brain of epileptic El mice. 140 65


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