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 effects of the serotonin (i.e. 5-hydroxytryptamine; 5-HT) S1 receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and the 5-HT precursor L-5-hydroxytryptophan (5-HTP) were compared in different models of epilepsy. 5-HTP significantly increased the threshold for electroconvulsions and pentylenetetrazol-induced seizures in mice and rats but exerted no anticonvulsant effects in epileptic gerbils and amygdaloid-kindled rats. The anticonvulsant effect of 5-HTP against electroconvulsions in rats could be attenuated by the S2 receptor antagonist, ketanserin. 8-OH-DPAT displayed no anticonvulsant effects in the seizure models examined but gave rise to proconvulsant effects in mice. Differences between 5-HTP and 8-OH-DPAT were also observed in terms of behavioural changes in response to both drugs. The data indicate that S2 receptors may be involved in the anticonvulsant effect of 5-HTP.
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PMID:Evaluation of the 5-hydroxytryptamine receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin in different rodent models of epilepsy. 293 61

The influence of antiepileptic drugs on the wet dog shakes (WDS) induced by intracerebroventricular injections of carbachol (30 micrograms icv) was investigated in rats. Diphenylhydantoin (DPH, 8 and 4 mg/kg), diazepam (0.4, 0.2 and 0.1 mg/kg), phenobarbital (12.5, 6.25 and 3.12 mg/kg), sodium valproate (Depakine, 200, 100 and 50 mg/kg) and trimethadione (200, 100 and 50 mg/kg) given ip inhibited the WDS in a dose-dependent manner. These drugs at the same doses did not change the intensity of shaking behavior induced by lithium chloride or 5-hydroxytryptamine. As the antiepileptic drugs tested in these experiments did not have anticholinergic activity and at used doses were not able to prevent electrical convulsions or pentetrazol-induced seizures, it appears that carbachol-induced WDS could be connected with convulsive activity and could be the initial stage of seizures.
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PMID:Inhibition by antiepileptics of carbachol but not lithium- or 5-methoxytryptamine-induced wet dog shakes in rats. 314 10

Inbred mutant El mice are highly susceptible to convulsive seizures upon 'throwing' stimulation, and the inhibition of 5-hydroxytryptamine (5-HT) and taurine activities appears to be involved in the El mouse seizures. Uptake and release of [3H]5-HT and [3H]taurine into and from cerebral neurocortical slices using a superfusion system were investigated in both non-stimulated and stimulated El mice [El(-), El(+)] and in ddY mice, which do not have a convulsive disposition. Release was defined as 40 mM K+-stimulated release. 5-HT and taurine uptake in El(+) was lower than El(-) but no difference in either uptake was found between ddY and El(-). Release of 5-HT and taurine in El(-) was higher than in ddY whereas their release in El(+) was lower than in El(-). The taurine level in the cerebral neocortex of El(-) and El(+) was higher than in ddY. These results suggest that the synaptic function of the 5-HT and taurine containing neurons is suppressed and that dysfunction of these inhibitory neurons is involved in the seizure susceptibility in the El mice.
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PMID:Reduced uptake and release of 5-hydroxytryptamine and taurine in the cerebral cortex of epileptic El mice. 350 82

alpha-Guanidinoglutaric acid (alpha-GGA) was first found in cobalt-induced epileptogenic focus tissue in the cerebral cortex of cats. We examined the effect of alpha-GGA on the electroencephalogram and on the brain 5-hydroxytryptamine (5-HT) level after intraventricular administration into rats. Sporadic low-voltage spikes appeared 4 min after the administration of alpha-GGA. Spikes increased in voltage 6 min after the administration. Multiple spikes appeared 10 min after the administration, and they reached maximal frequency 30 min after the administration. The epileptic discharges disappeared 100 min after the administration. The 5-HT level increased in the right and left cortices 3 min after the administration. The 5-HT level decreased in the mid-brain 5 min after the administration and subsequently in all regions of the brain 10 min after the administration. No change in the 5-HT level was found 30 min and 100 min after the administration. These results show that alpha-GGA induces epileptic seizures in rats after intraventricular administration. The results also suggest that alpha-GGA-induced seizures are associated with abnormal serotonergic function and that they are initiated by a decrease in the 5-HT level.
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PMID:Convulsive activity of alpha-guanidinoglutaric acid and the possible involvement of 5-hydroxytryptamine in the alpha-guanidinoglutaric acid-induced seizure mechanism. 377 79

We previously reported that 6-methoxy-1,2,3,4-tetrahydro-beta-carboline (6-MeO-THBC) attenuated audiogenic seizures (AGS) in 21-day-old DBA/2J mice and also inhibited brain monoamine oxidase-A (MAO-A) and serotonin (5-hydroxytryptamine, 5-HT) uptake leading to increased brain 5-HT concentration. In this study, the sensitivity of AGS to 5-HT manipulation was evaluated by utilizing drug combinations which paralleled the actions of 6-MeO-THBC and which also have been associated with the production of a serotonergic motor syndrome in rats. Combination of a specific 5-HT uptake inhibitor (fluoxetine or citalopram) with the MAO-A inhibitor clorgyline inhibited AGS more effectively than the individual drugs but combination with the MAO-B inhibitor deprenyl did not. Combined administration of clorgyline plus deprenyl also suppressed AGS. Inhibition of AGS by tryptophan was potentiated by combination with either of the mixed MAO inhibitors nialamide or tranylcypromine. The effects of these drugs individually and in combination on brain MAO-A and MAO-B activity and 5-HT uptake were also determined ex vivo and were consistent with expected mechanisms of action. These results suggest, first of all, that the inhibition of AGS produced by 6-MeO-THBC is a consequence of its combined MAO-A and 5-HT uptake inhibition properties. Secondly, the similarity of results of pharmacological manipulations of the 5-HT system which produce the rat motor syndrome and which inhibit AGS in the mouse suggests that AGS in 21-day-old DBA/2J mice may be a useful system for assessing functional consequences of these serotonergic manipulations.
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PMID:Combined inhibition of serotonin uptake and oxidative deamination attenuates audiogenic seizures in DBA/2J mice. 408 Jul 61

The effect of L-5-hydroxytryptophan (5-HTP) on the threshold for maximal electroconvulsions was compared with concomitant changes in levels of 5-HTP, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in plasma and brain of rats. A single injection of 5-HTP (100 mg/kg, i.p.) caused significant elevation in seizure threshold which was markedly intensified by pretreatment with the decarboxylase inhibitor carbidopa (10 mg/kg, i.p., 0.5 hr previously). Pretreatment with carbidopa also resulted in behavioural changes, i.e. the characteristic "wet-dog shake" behaviour became much more prominent. Biochemically, administration of 5-HTP gave rise to significant elevation of levels of 5-HTP, 5-HT and 5-HIAA in plasma and brain. Carbidopa increased levels of 5-HTP in the brain, decreased 5-HIAA in the periphery but did not alter the elimination rate of 5-HTP in plasma. In both naive rats and rats pretreated with carbidopa, a significant correlation was found between levels of 5-HTP and 5-HIAA in plasma and brain following injection of 5-HTP. Furthermore, in the absence of carbidopa, the increases of levels of 5-HT in plasma and brain induced by 5-HTP were correlated in a significant fashion. When the changes in the electroconvulsive threshold were compared with respective changes in levels of 5-hydroxyindoles, a significant correlation was obtained between threshold elevations and increases of 5-HTP and 5-HT in the brain. In rats treated with 5-HTP, without decarboxylase inhibitor, a significant correlation was found between increases in 5-HT in plasma and the seizure threshold. The results suggest that analysis of 5-hydroxyindoles in plasma may represent a useful tool for the estimation of 5-HT metabolism in brain.
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PMID:L-5-hydroxytryptophan. Correlation between anticonvulsant effect and increases in levels of 5-hydroxyindoles in plasma and brain. 608 1

Stimulation of GABA receptors (e.g. by progabide, a new GABA receptor antagonist, or by muscimol) enhances the liberation of norepinephrine in limbic forebrain areas of the rat and reduces 5-hydroxytryptamine turnover. On repeated administration, this latter effect is associated with an up-regulation of 5-HT2 receptors as it occurs after electroconvulsive shock. The monoaminergic changes induced by progabide, though dissimilar from those induced by tricyclics, are probably connected with the antidepressant action on the compound observed in double-blind clinical trials. In the basal ganglia, GABA receptor agonists reduce dopamine turnover and potentiate the cataleptogenic action of neuroleptics. They also antagonize the sterotypic behaviour induced by dopaminomimetics, indicating an additional action beyond the dopamine synapse. On repeated co-administration with neuroleptics, progabide antagonizes the tolerance to the cataleptogenic action, the supersensitivity to dopaminomimetics, and the increase in 3H-spiperone binding which are caused by sustained neuroleptic treatment. This appears to be the basis for the clinical action of progabide in neuroleptic-induced dyskinesia, L-dopa-induced involuntary movements, and possibly mania. GABA receptor agonists decrease cellular excitability in several animal models and antagonize seizures, whatever their origin (GABA-mediated or GABA unrelated mechanisms). Progabide has been shown to be effective in various forms of epilepsy in double-blind and long-term clinical trials. The compound exerts a therapeutic action in patients resistant to "classical" antiepileptic drugs, in the virtual absence of major side effects.
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PMID:Pharmacology of the GABAergic system: effects of progabide, a GABA receptor agonist. 608 42

The effect on audiogenic seizures of drug-induced increments in biogenic amines in the brain was determined in DBA/2J mice. One group of mice was treated with L-dihydroxyphenylalanine (L-DOPA) which caused a large rise in levels of norepinephrine and dopamine in the central nervous system, but did not significantly alter the concentration of 5-hydroxytryptamine. This group of animals exhibited a dramatic reduction in the incidence of tonic extensor seizures. A second group of animals that had been pretreated with diethyldithiocarbamate, a dopamine-beta-hydroxylase inhibitor, was also given L-DOPA. In this group of mice, there was a highly significant rise in the concentration of dopamine in brain but no statistically-significant changes in levels of either norepinephrine or 5-hydroxytryptamine. These animals also had a dramatic decrease in the incidence of tonic extensor seizures. A third group of animals that received only diethyldithiocarbamate did not exhibit any statistically-significant changes in the incidence of seizure or in levels of biogenic amines. The drug-induced reduction in the incidence of seizure in the first two groups correlated with a large increase in levels of dopamine in brain. This reduction in seizures did not correlate with changes in levels of norepinephrine or 5-hydroxytryptamine in brain.
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PMID:Effect of increments in the concentration of dopamine in the central nervous system on audiogenic seizures in DBA/2J mice. 609 54

Young adult Louis rats were implanted for chronic sleep recording to test the effect of diethyldithiocarbamate (DDC) on sleep. Recordings of EEG and EMG were done continuously for 12 h during the 12 consecutive days. There were 2 days of baseline recording, 3 days of recording with a single daily injection of placebo, 3 days of recording with a single daily injection of DDC (500 mg/kg i.p.), and 3 days of DDC withdrawal recording with placebo injection. Placebo injections did not change the proportion of time spent in different behavioural states. With daily injection of DDC there was an increase in wakefulness, no change in slow-wave sleep and elimination or drastic reduction in paradoxical sleep (PS). There was no PS rebound during the DDC withdrawal days. These results suggest that the reduction of PS produced by DDC and the absence of PS rebound may be due to a lowering in norepinephrine in the brain. In other experiments rats were injected with DDC (500 mg/kg i.p.) daily for 3 days and whole brains were analysed chemically. Norepinephrine was significantly decreased, while 5-hydroxytryptamine, 5-hydroxyindolacetic acid, dopamine and homovanilic acid were unchanged. Seizure activity appeared during relaxed wakefulness in all rats treated with DDC. Taken together it seems that lowering of brain NE is responsible for the appearance of seizure activity and also, for PS reduction. PS reduction might, per se, produce seizure activity.
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PMID:Sleep-waking cycle and behaviour after diethyldithiocarbamate in the rat. 615 81

The effects of fluoxetine [an inhibitor of 5-hydroxytryptamine (5-HT) reuptake] on electrically-induced spinal cord seizures were determined by monitoring alterations in the total duration of seizure, as well as the durations of tonic flexion and extension. The capacity of fluoxetine to inhibit 5-HT reuptake in the spinal cord was confirmed by measurements of 5-hydroxyindoleacetic acid (5-HIAA) content. When given in a dose of 10 mg/kg, fluoxetine failed to produce an effect on spinal cord seizures or on 5-HIAA content. However, a dose of 20 mg/kg did significantly reduce 5-HIAA content although it did not alter seizure activity. These results further support our earlier suggestion that 5-HT containing neurons in the spinal cord do not modulate electrically-induced seizures.
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PMID:Effects of fluoxetine on electrically-induced spinal cord seizures in rats. 615 71


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