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)

To assess the possible role of amine neurotransmitters in human epilepsy, we measured metabolites of serotonin (5-hydroxyindoleacetic acid [5-HIAA]), dopamine (homovanillic acid [HVA]), and norepinephrine (3-methoxy-4-hydroxyphenylethylene glycol [MHPG]) in the lumbar cerebrospinal fluid (CSF) of patients with partial complex seizures and in neurologic controls. Untreated epileptic patients had lower concentrations of 5-HIAA and HVA in the lumbar CSF than the controls, but the differences were not statistically significant. Among epileptic patients receiving effective antiepileptic drug treatment, the HVA concentration was within the control range. Mean MHPG concentrations were similar in patients and controls. From the epileptic patients whose CSF was obtained at pneumoencephalography we obtained a second sample of CSF that was originally in the basal cisterns. No significant differences between treated and untreated patients were found for any of the three metabolites. The concentrations of HVA and 5-HIAA were higher in cisternal than in lumbar CSF, but there was no such gradient for MHPG.
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PMID:Monoamine metabolites in the CSF of epileptic patients. 3 60

The time course of changes in behaviour, seizure response and cerebral monoamine and gamma-aminobutyric acid (GABA) metabolism has been studied in relation to the anticonvulsant actions of di-n-propylacetic acid (DPA) and ethanolamine-O-sulphate (EOS) on sound-induced seizures in DBA/2 mice. Changes in cerebral monoamine metabolism after EOS (75 or 150 mug, intracerebroventricularly) were not related to its anticonvulsant action. The primary effect was GABA-transaminase inhibition (by 50-70%) leading to a 2-4 fold increase in cerebral GABA concentration. Increases in brain GABA concentration (maximally 36%), 5-hydroxyindoleacetic acid (5HIAA, maximally 134%) and homovanillic acid (HVA, maximally 183%) were seen after DPA (400-600 mg/kg, i.p.). The time course of the increases in HVA and 5HIAA did not correlate with the anticonvulsant effect. Elimination of these increases by the use of inhibitors of monoamine synthesis (alpha-methyl-p-tyrosine and p-chlorophenyl-alanine) did not alter the anticonvulsant effect of DPA. Experiments using probenecid suggested that the increases in 5HIAA and HVA after DPA result from inhibition of their active transport out of the brain.
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PMID:Monoamine and GABA metabolism and the anticonvulsant action of di-n-propylacetate and ethanolamine-O-sulphate. 13 17

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

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

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

Chronic administration of the same dose of cocaine to rhesus monkeys for up to 6 months was associated with progressive alterations in pathological behavior and increased susceptibility to seizures. Monkeys initially displaying prominent hyperactive stereotypic responses for up to 2 months began to demonstrate increasing amounts of inhibitory behavior, consisting of catalepsy, motor inhibition, and abnormal visual tracking and staring. Four of 13 animals developed increasing intensities of lingual-buccal dyskinesias after 10 weeks of chronic cocaine. Animals initially showing no convulsions to a given dose of cocaine eventually developed convulsions to the same dose, and then displayed an increased frequency of convulsions following subsequent injections. Levels of the dopamine metabolite, homovanillic acid (HVA), in the cisternal cerebrospinal fluid were significantly elevated during both excitatory stereotypic and inhibitory syndromes; a similar trend was observed for HVA after probenecid administration. Only the probenecid-induced accumulations of the serotonin metabolite 5-hydroxyindoleacetic acid, following acute cocaine administration, were significantly elevated. The progressive increases in convulsions, dyskinesias, and the inhibitory syndrome did not appear related to alterations in peak levels of cocaine in plasma or CSF, and a pharmacological kindling model is suggested as an alternate explanation of the data. The study extends the current models of stimulant-induced psychoses by highlighting the progressive alterations in behavior and neurological sequelae and in suggesting that this progressive mechanism may also be important in the development of psychosis in man.
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PMID:Progressive effects of cocaine on behavior and central amine metabolism in rhesus monkeys: relationship to kindling and psychosis. 82 87

6-Methoxy-1, 2, 3, 4, -tetrahydro-beta-carboline (6-MeO-THBC) was tested for anticonvulsant properties against audiogenic seizures in DBA/2J and primed C57BL/6J mice (i.e., mice given a prior auditory exposure) and aginast electroconvulsive seizures in DBA/2J mice. 6-MeO-THBC (100 mg/kg) was found to attenuate both types of behavioral seizures 2 hr after injection as compared to saline controls. In addition, 6-MeO-THBC increased whole brain serotonin and decreased whole brain 5-hydroxyindoleacetic acid 2 hr after injection. These results support previous reports which suggest a serotonergic involvement in behavioral seizures.
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PMID:Anticonvulsant effects of 6-methoxy-1, 2, 3, 4-tetrahydro-alpha-carboline on audiogenic and electroconvulsive seizures in mice. 112 56

Children with infantile spasms (IS) are generally treated with ACTH although little is known of the biochemical basis of the symptoms and the mechanism of this therapy. We have measured the concentrations of gamma-aminobutyric acid (GABA), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the CSF of IS children, followed the effect of ACTH treatment on these parameters and correlated CSF GABA values with the cause of IS, cranial CT findings and antiepileptic treatment. While significant differences in GABA concentrations were found between the children with IS and those with febrile seizures or nonconvulsive symptoms, these could be accounted for by age, not the disease present. The CSF GABA level was highest in the IS children with normal CT, cryptogenic cause and no antiepileptic treatment, and lowest in those with abnormal CT, symptomatic cause and antiepileptic treatment. The basal level of CSF 5-HIAA in the IS children was higher than that in the nonconvulsive children, but HVA levels did not differ. ACTH therapy did not change the CSF levels of GABA, 5-HIAA and HVA significantly.
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PMID:The concentrations of GABA, 5-HIAA and HVA in the cerebrospinal fluid of children with infantile spasms and the effects of ACTH treatment. 128 5

This study examined the effects of electroconvulsive shock (ECS) on interstitial concentrations of serotonin (5-HT), its metabolite 5-hydroxyindoleacetic acid (5-HIAA), acetylcholine and choline, and the dopamine metabolite homovanillic acid (HVA) in the hippocampus of freely moving rats using online brain microdialysis. The effects of ECS on 5-HT, 5-HIAA, and HVA were compared to the effects of seizures induced by the convulsant agent flurothyl. Interstitial concentrations of 5-HT increased several fold in response to ECS and this increase was accompanied by a significant increase in the concentration of HVA. Acetylcholine and choline concentrations were also increased significantly by ECS. The ECS-induced increase in interstitial 5-HT was markedly reduced when the voltage-dependent sodium channel blocker tetrodotoxin (1 mumol/L) was added in the perfusion solution, indicating that the observed increase was of neuronal origin. Interstitial concentrations of 5-HT also increased in response to flurothyl-induced seizures and this increase was accompanied by a significant increase in the concentration of HVA. These results provide direct in vivo evidence that interstitial concentrations of 5-HT increase several fold in response to both ECS- and flurothyl-induced seizures. These observations are discussed in relation to the hypothesized role of 5-HT in ECS-induced memory deficits.
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PMID:Neurochemical effects of electrically and chemically induced seizures: an in vivo microdialysis study in the rat hippocampus. 138 32

Cerebrospinal fluid (CSF) from 6 cases of asymptomatic infantile spasms (IS) (mean age, 6.1 months) was collected before and after treatment with adrenocorticotropic hormone (ACTH). The concentration of CSF tryptophan (TRP) metabolites was analyzed using HPLC and compared to the metabolite concentration in CSF from 10 age-matched controls (mean age, 6.7 months). Levels of CSF serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and kynurenine (KYN) at pretreatment were significantly lower in IS patients compared to controls (p < 0.05). In contrast, the levels of CSF 3-hydroxykynurenine (3-OHKY) before ACTH treatment were significantly higher in IS patients than in controls (p < 0.05). After the treatment, significant increases in 5-HIAA and decreases in KYN and 3-OHKY levels (p < 0.05) were observed in CSF of infants whose seizures were eliminated by ACTH. These findings suggested that the presence of seizures in IS was associated with a significant decrease in serotonergic activity, or that the turnover in the direction of 3-OHKY was altered. The possibility that elimination of seizures by ACTH might be related to decreased production of kynurenine metabolites was discussed.
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PMID:[Changes in CSF tryptophan metabolite levels in infantile spasms]. 141 65


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