Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We used limbic seizures induced in rats by systemic injection of the cholinergic agonist pilocarpine (380 mg/kg; i.p.) to study the neuronal pathways within the basal ganglia that modulate seizure threshold. N-Methyl-D-aspartate (N-Me-D-Asp) is an excitatory amino acid derivative that is a powerful convulsant agent when injected into the cerebral cortex, amygdala, or hippocampus in rats. Bilateral microinjections of N-Me-D-Asp into the caudate-putamen, however, protected against limbic seizures induced by pilocarpine (injected systemically), with an ED50 of 0.7 nmol (range 0.5-1.0 nmol). Lesioning the caudate-putamen (by bilateral microinjection of the excitotoxin ibotenate) converted subconvulsant doses of pilocarpine into convulsant ones. The anticonvulsant action of N-Me-D-Asp in the caudate-putamen was reversed by blocking gamma-aminobutyrate-mediated inhibition in the substantia nigra pars reticulata or in the entopeduncular nucleus. The results suggest that the caudate-putamen and its gamma-aminobutyrate-dependent efferent pathways modulate the threshold for seizures in the limbic forebrain.
 ...
PMID:Paradoxical anticonvulsant activity of the excitatory amino acid N-methyl-D-aspartate in the rat caudate-putamen. 355 Jul 95

The omega-phosphono-alpha-aminocarboxylic acids, e.g., 2-amino-5-phosphonopentanoate and 2-amino-7-phosphonoheptanoate, are known to act as potent and selective antagonists at N-methyl-D-aspartate receptors and to have a pronounced anticonvulsant action on a variety of animal models of epilepsy. In the present study, the effects of these omega-phosphono-alpha-aminocarboxylic acids on E1 mice were investigated. These mice are inbred mutant epileptic mice, which are highly susceptible to convulsive seizures upon throwing stimulation. 2-Amino-3-phosphonopropionate injected intraventricularly (at a dose of 1.04 mumol) had a marked anticonvulsant action, but at a lower dose (0.1 mumol), it induced running fits. 2-Amino-4-phosphonobutyrate induced transitory excitation just after the injection, followed by sedation. 2-Amino-5-phosphonopentanoate induced marked behavioral sedation. 2-Amino-6-phosphonohexanoate induced tonic-clonic convulsions and epileptic discharges in electroencephalograms. 2-Amino-7-phosphonoheptanoate showed a strong anticonvulsant action at a dose of 1.27 mumol, but it induced myoclonic seizures at a lower dose. Amino acid analyses of E1 mouse brain showed that 2-amino-3-phosphonopropionate increased the glutamine level, 2-amino-4-phosphonobutyrate decreased the aspartic acid level, 2-amino-5-phosphonopentanoate decreased the glutamic acid level, 2-amino-6-phosphonohexanoate decreased the glutamic acid, glutamine, gamma-aminobutyric acid, glycine and alanine levels, and 2-amino-7-phosphonoheptanoate decreased the glutamic acid label 1 hour after their injection. These findings suggest that the effects of omega-phosphono-alpha-aminocarboxylic acids on the E1 mouse brain are multiple and complicated, depending on the numbers of their carbon chain.
 ...
PMID:The effect of omega-phosphono-alpha-aminocarboxylic acids on seizures and brain amino acid levels in E1 mice. 367 86

Extracellular levels of amino acids were estimated in dialysates of the rat striatum that were collected 1, 2, and/or more than 5 days after surgery, before (resting release) and during exposure to high K concentrations (50 mM) or electroconvulsive shocks. The resting release of several amino acids (Glu, Asn, Thr, Tau, Tyr, Gly, and Ala) was higher 9 days as compared to 1 day after surgery. In the 1-day preparation the resting release correlated highly with that observed with push-pull cannulas. The correlation with the tissue content of the amino acids was high only when they were divided into two groups (putative transmitters and metabolic intermediates). High K exposure produced increased output of Ala, ethanolamine (Eam), Asp, Glu, Tau, and Gly and a decrease in the egress of Gln 1 or 2 days after surgery. The effects on Asp and Glu had disappeared, and that on Gln reversed after 4-9 days. Electrically induced convulsions produced increased output of Ala, Gln, and Eam 1 or 2 days and 2 weeks after implantation of the probe. Changes were seen not only during but also (and some cases even more prominent) after the seizure. This study shows the usefulness of dialysis to monitor extracellular transmitter amino acids in the striatum of conscious rats (also bilateral dialysis was possible) for only a limited time after implantation of the probe. The dialysis method is suitable for longer time, when metabolic changes in amino acids are to be followed. In addition to transmitter release, glycolysis can be monitored by the measurement of Ala in the dialysate.
 ...
PMID:Amino acids in rat striatal dialysates: methodological aspects and changes after electroconvulsive shock. 404 52

Evidence of genetic factors in seizure disorders by examination of plasma amino acid concentrations in multiply affected sibships was investigated. The strategy of multiply affected sibship ascertainment was used to reduce heterogeneity as one of several potential sources of variation in quantitative amino acid levels. Our results do not support previously reported increases in plasma taurine, aspartic acid, or glutamic acid in seizure patients. However, we do find that multiply affected sibships have significantly elevated plasma concentrations of arginine and asparagine, and significantly decreased ornithine. These amino acid concentrations may be under quantitative genetic control. Within-sibship comparisons indicate that seizure patients have increased glutamine and decreased lysine and phenylalanine, possibly secondary to the seizures. We also find that anticonvulsant use complicates statistical analyses. Further studies to more clearly delineate the genetics of plasma amino acid concentrations (or other quantitative metabolic measures) and their role in seizure disorders are required and will benefit from the use of a homogeneous sampling strategy.
 ...
PMID:Altered amino acid levels in multiply affected sibships with seizures. 407 67

In rabbits, generalized seizures were induced by methoxypyridoxine, and changes in amino acid concentrations of 15 brain regions were investigated before seizure onset and during the course of sustained epileptiform activity. As previously reported, gamma-aminobutyric acid (GABA) concentration decreased preictally in most regions. At the same time, taurine level was elevated in the hypothalamus, thalamus, hippocampus, caudatum, and frontal cortex. After 90 min of seizures, it was significantly decreased in the hypothalamus, periaqueductal grey, substantia nigra, frontal cortex, and cerebellum. Glycine content was reduced preictally only in the substantia nigra; after seizure onset its concentration rose in all brain areas. Glutamate content in the frontal cortex decreased before seizure onset; after 1.5 h of seizures, its concentration in cerebellum, caudatum, and hippocampus was reduced. Aspartate level was decreased in most areas after sustained seizures; in putamen, however, it was elevated. In contrast, glutamine content increased preictally in the superior colliculus and in all brain areas by approximately 200% after 90 min of seizures. Alanine and valine content also rose markedly in most brain areas after prolonged seizures, and threonine showed the same tendency. The single brain regions were observed to respond to methoxypyridoxine in highly individualistic ways. For example, the glycine content of the substantia nigra, which is believed to utilize this amino acid as a neurotransmitter, decreased preictally. The potential importance of the superior colliculus in seizure induction is considered in view of the early rise in glutamine level. The antagonistic preictal behavior of taurine and GABA is discussed with respect to synthesis, uptake from the blood, and antiepileptic properties.
 ...
PMID:Alterations in the content of amino acid neurotransmitters before the onset and during the course of methoxypyridoxine-induced seizures in individual rabbit brain regions. 613 13

The amygdalas of rats were stimulated daily to produce kindled epilepsy. Superfusion of the ipsilateral ventricle allowed collection of amino acids before, during and after stimulation. At the stage where stimulation evoked full seizures there was a correlated increase in the extent of glutamate release. Other amino acids, including aspartate, showed no significant changes at this time. Aspartate, threonine and serine showed smaller responses not significantly different from those seen at the pre-kindled stage. Antagonists of excitatory amino acids (omega-phosphono-alpha-amino dicarboxylic acids) effectively antagonized both the behavioral and electrical components of the kindled seizures.
 ...
PMID:The kindled amygdala model of epilepsy: anticonvulsant action of amino acid antagonists. 613 23

Two new phosphonate dipeptides, gamma-D- glutamylaminomethylphosphonate (Glu-Amp) and beta-D- aspartylaminomethylphosphonate (Asp-Amp), that are antagonists of excitation due to N-methyl-D-aspartate have been compared with omega-phosphonic-alpha-carboxylic amino acids as anticonvulsant agents in mice with sound-induced seizures. Compounds were injected intracerebroventricularly (i.c.v.) or intraperitoneally (i.p.) into DBA/2 mice 45 min prior to sound exposure, and ED50 values for suppression of the different phases of the seizure response were estimated. With i.c.v. injection Glu-Amp is 0.4-0.8 times as potent an anticonvulsant as (+/-)2-amino-7- phosphonoheptanoate and Asp-Amp is 1.3-2.5 times as potent. With i.p. injection Glu-Amp is 0.15-0.28 and Asp-Amp 0.23-0.58 times as potent as (+/-)2-amino-7-phosphonoheptanoic acid. These findings correspond to their known potency as N-methyl-D-aspartate antagonists, and are consistent with an anticonvulsant effect arising from action at a receptor sensitive to N-methyl-D-aspartate.
 ...
PMID:Suppression of audiogenic seizures in DBA/2 mice by two new dipeptide NMDA receptor antagonists. 614 26

Aspartic acid concentration in CSF was markedly elevated in a newborn infant with severe, intractable seizures. The levels of all other amino acids in blood, urine, and CSF were within the normal range. Two of the six other siblings in this consanguineous family died in early infancy of a similar condition. Since aspartic acid is a putative excitatory neurotransmitter, a possible causal relationship is suggested between its increased CSF concentration and the occurrence of neonatal convulsions in this family.
 ...
PMID:A possible role for aspartic acid in neonatal seizures. 721 51

This paper analyzes the effect of conventional (phenobarbital, phenytoin, carbamazepine, ethosuximide, valproate) and some novel (vigabatrin, lamotrigine, felbamate) AEDs on some basic mechanisms involved in focal and/or generalized epileptogenesis (Na+ voltage-dependent channels and sustained repetitive firing, L-, N-, and T-type Ca2+ currents, GABA-mediated inhibition, Glu/Asp-mediated excitation, after-hyperpolarization). According to this analysis, AEDs can be divided into two main categories, those with only one specific action and those with multiple actions. A speculative correlation is proposed between AED effects on the mechanism of epileptogenesis and their known clinical effect on seizures.
 ...
PMID:Antiepileptic drugs and mechanisms of epileptogenesis. A review. 759 73

Propofol (i.v. and i.p.) exhibited anticonvulsant activity in three models of seizure in the mouse, induced by bicuculline, kainic acid and N-methyl-DL-aspartic acid (NMDLA). Morphine, pethidine and fentanyl, which showed a biphasic dose-response relationship with respect to seizure modulation, abolished the anticonvulsant activity of propofol to exhibit their own intrinsic activity in proconvulsant doses. This occurred with very low doses of fentanyl and pethidine (15 micrograms kg-1 and 0.5 mg kg-1, respectively) in the NMDLA model. Thus it appears that propofol has anticonvulsant activity only when a convulsion is elicited directly; it does not prevent the actions of compounds that lower seizure threshold to convulsant stimuli. The anticonvulsant doses of morphine and fentanyl did not summate with the anticonvulsant activity of propofol. However, there was some evidence of summation of anticonvulsant activity between pethidine and propofol in the NMDLA model.
 ...
PMID:Interactions between opioid drugs and propofol in laboratory models of seizures. 771 78


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>