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)

Looking for the 'epilepsy gene', we used ddY derived, genetically seizure-susceptible El mice. To find biochemical abnormalities, we examined the amino acid metabolism and gene activity, including poly(A)+ RNA and sodium channel mRNA expressions, in the developmental growth of El mice. At the early postnatal stage, abnormalities in amino acid metabolism were aberrant free amino acid fluctuations. Almost all free amino acids in the liver of newborn El mice showed considerably lower levels than did ddY mice. Among those amino acids, Asp, Glu and Tyr were extremely low, but rapidly recovered to the ddY level within a week. During the successive growth period, we observed no significant difference in hepatic amino acid levels between El and ddY mice. No such drastic changes were noted in the amino acid levels in the brains of ddY and El mice; only the Gly level was greater in El mice than in ddY mice on the day of birth. Rotatory stimulation which evokes convulsions in El mice but not in ddY mice was applied to adult mice and changes in the amino acid level were assessed. The level of Glu and Tyr in seizure-induced El mice was approximately twice that noted in the liver and brain of El mice, which did not experience seizures. It was also somewhat increased in ddY mice subjected to rotational stress which did not induce seizures in that strain. Gene activity that expresses poly(A)+ RNAs, including sodium channel mRNA, was determined by Northern blot analysis, which reveals unscheduled mRNA synthesis by the appearance of an extra band approximately 3 kb in size.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Unusual biochemical development of genetically seizure-susceptible El mice. 166 88

The levels of inhibitory amino acids (Tau, Gly), or excitatory amino acids (Glu, Asp) and Gln, precursor of GABA, have been determined, under resting conditions, in 17 brain areas of 3 sublines of inbred Rb mice displaying different responses to an acoustic stimulus. Rb1 mice were clonictonic seizure-prone, Rb2 mice were clonic seizure-prone and Rb3 mice were seizure resistant. Profile of distribution in the brain of each one of these amino acids differed. Maximum to minimum level ratio was higher for Tau (3.8) than for Glu or Asp or Gln (2). The level of Gly was similar in 13 out of the 17 areas examined. Multiple inter-subline differences were recorded for each amino acid. These differences have been analyzed considering the seizure susceptibility or severity of the three Rb sublines. Common lower levels (approximately -20%: Rb1/Rb3, Rb2/Rb3) of Gln in Temporal Cortex may be implicated in seizure susceptibility. Seizure severity (Rb1/Rb2) seems to correlate, in some areas, with additional lower amounts of GABA already reported and, to a lower extent, of Asp (-19% in striatum, inferior colliculus and cerebellum), of Tau and Gly; a tendency for a rise in Gln content was observed in certain others (10-20% in olfactory bulb, thalamus, hypothalamus, substantia nigra, and frontal, temporal and occipital cortex). The data and correlations recorded provide guidelines for further investigations for synaptosomal and metabolic alterations in the three sublines of the same strain of Rb mice.
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PMID:Amino acid neurotransmitter alterations in three sublines of Rb mice differing by their susceptibility to audiogenic seizures. 197 52

This study evaluates the glycine potentiation of anticonvulsant drugs in subcutaneous pentylenetetrazol seizures in rats. Administered alone, glycine (30 or 40 mM/kg, PO) induced no anticonvulsant effect or neurological deficit. Coadministered with anticonvulsants, glycine significantly enhanced the anticonvulsant potency of diazepam and sodium valproate without affecting the neurological deficit induced by the anticonvulsants. Glycine did not significantly alter the anticonvulsant activity of ethosuximide or phenobarbital. These findings indicate a possible glycine-sensitive component in the mechanism of action of diazepam and sodium divalproate in subcutaneous pentylenetetrazol seizures. With the possible exception of sodium valproate, the present study provides little support for a glycine and gamma-aminobutyric acid (GABA) interaction as a mechanism of anticonvulsant activity in SC PTZ seizures. Further studies are required to determine the role of strychnine-sensitive and strychnine-insensitive glycine receptors in this experimental model of absence epilepsy.
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PMID:Glycine potentiation of anticonvulsant drugs in pentylenetetrazol seizures in rats. 201 17

Vigabatrin, because of its ability to increase brain GABA concentration, acts as an anticonvulsant on convulsive epileptic seizures and increases seizures in generalized non-convulsive epilepsy. Next to GABA, glycine is one of the most important inhibitory neurotransmitter amino acids. We studied the influence of glycine on the effects of treatment with vigabatrin in two rat models of generalized convulsive seizures and a rat model of spontaneous generalized non-convulsive seizures. Glycine (750 mg/kg i.p.) or vigabatrin (200 mg/kg i.p.), when given alone, provided partial protection against convulsive seizures, while combined treatment with the two drugs significantly suppressed the convulsive seizures in both the mercaptopropionic acid (MPA)-induced seizures and audiogenic seizures. In contrast to the response to treatment with each individual drug, the drug combination nearly abolished the appearance of isolated spikes on the EEG in MPA seizures. On the other hand, glycine also enhanced the aggravating effect of vigabatrin on spontaneous spike and wave discharges in a rat model of genetic absence epilepsy, whereas glycine or vigabatrin alone, at the above doses, produced only a slight, non-significant increase in spontaneous spike and wave discharges. The GABA-glycine interaction is the first example of a synergistic action of two inhibitory neurotransmitters on seizure-related pathological discharges.
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PMID:Potentiation of gamma-vinyl GABA (vigabatrin) effects by glycine. 211 8

D-Tyr-Ser-Gly-Phe-Leu-Thr (DSLET), beta-endorphin, morphiceptin and morphine were microinjected at 48-h intervals into the amygdala or hippocampus of awake rats in an attempt to identify the opiate receptor types involved in opioid kindling. DSLET, beta-endorphin, morphiceptin and morphine were injected into the lateral ventricle to assess the possibility of kindling seizures by this route. The delta-receptor agonist DSLET effectively kindled convulsions when microinjected into amygdala or ventral hippocampus. The convulsions were suppressed or strongly attenuated by ICI 174,864, a specific antagonist of the delta-receptor, microinjected into the same brain site, but were not affected by ICI 174,864 administered peripherally. When microinjected into amygdala or hippocampus, beta-endorphin and morphiceptin also kindled convulsions, which were antagonized by naloxone but not by ICI 174,864. Morphine evoked EEG epileptiform activity but did not kindle convulsions from limbic brain sites. DSLET occasionally evoked epileptiform spiking and submaximal convulsions when injected into ventricle, and morphiceptin evoked epileptiform spiking only, but tolerance to these effects occurred after repetition of the injections. Thus, convulsions can be kindled by activation of either mu-, delta- or epsilon-receptors when opioids are injected directly into limbic tissue. However, the ability of these compounds to kindle seizures is markedly reduced when they are administered into ventricle. The striking differences between the present results and previous results obtained by peripheral or intraventricular administration of opioid peptides suggest that the route of administration, among other variables, is a crucial factor in assessing the epileptogenic properties of opioid peptides.
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PMID:Involvement of multiple opiate receptors in opioid kindling. 216 33

This study evaluated the potentiation by glycine of anticonvulsant drugs in maximal electroshock seizures in rats. Administered alone, glycine (40 mmol/kg, p.o.) induced no anticonvulsant effect or neurotoxicity. Administered together with the anticonvulsants, glycine significantly enhanced the anticonvulsant potency of phenobarbital and carbamazepine. Glycine also potentiated the anticonvulsant actions of MK-801 and diazepam but did not improve the selectivity of the drugs, as effective doses were still associated with neurotoxicity. Glycine did not potentiate phenytoin or sodium divalproate. Administration together with glycine had no significant effect on the concentrations of phenobarbital or carbamazepine in the brain. Administration together with phenobarbital had no relevant effect on the concentration of glycine in the brain but administration of glycine and carbamazepine together resulted in an increased concentration of glycine in the hippocampus and brainstem. These findings indicate a possible glycine-sensitive component in the mechanism of action of phenobarbital, carbamazepine and diazepam in maximal electroshock seizures. Although the mechanism may not be mediated by a glycine-GABA interaction, the evidence does implicate a possible interaction between glycine and anticonvulsant drugs at NMDA receptors.
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PMID:Potentiation by glycine of anticonvulsant drugs in maximal electroshock seizures in rats. 234 38

It is well known that a dietary restriction of vitamin B-6 during gestation and lactation produces spontaneous seizures in neonatal animals. Since pyridoxal phosphate, one of the biologically active forms of vitamin B-6, is the cofactor for GAD the neonatal seizures have been attributed to low levels of brain GABA as a result of cofactor depletion. Although GABA levels are significantly lower in B-6 restricted neonatal rats with spontaneous seizures, seizure activity is not present in B-6 deficient adult rats or 28 day old rats in the present study, despite significantly low levels of brain GABA. These facts suggest that depletion of GABA is not the only biochemical alteration essential for the emergence of seizures. In the present study, the effect of vitamin B-6 undernutrition on the concentrations of the neuroactive amino acids, Glu, Gly, Tau, and GABA was determined in selected regions of the developing rat brain. The results show that the concentrations of Glu, Tau, and GABA were significantly lower and GLY significantly higher in selected brain regions of the B-6 restricted 14 day old rat compared to control tissue. Most of these changes were unique to 14 days of age, the time when spontaneous seizures are observed, and not present at 28 or 56 days of age when seizures are absent. This pattern of amino acid changes in the brain and the magnitude of the changes was consistent with those measured in a variety of chemically-induced animal models of epilepsy and in human epileptic foci.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regional changes in the concentrations of glutamate, glycine, taurine, and GABA in the vitamin B-6 deficient developing rat brain: association with neonatal seizures. 257 23

Betaine (N,N,N-trimethylglycine) and N,N-dimethylglycine have been reported to have anticonvulsant properties in animals. The purpose of the present study was to determine whether these compounds can antagonize strychnine-induced seizures when administered intraperitoneally and to compare their effects with those of sarcosine (N-methylglycine) and glycine. Betaine, N,N-dimethylglycine and sarcosine were equipotent in decreasing the incidence of seizures and death, causing a 38 to 72 percent decrease in the incidence of seizures and death at a dosage of 5 mmole/kg. Glycine had no effect. Thus anticonvulsant activity is conferred to glycine by a single N-methylation.
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PMID:Prevention of strychnine-induced seizures and death by the N-methylated glycine derivatives betaine, dimethylglycine and sarcosine. 258 Dec 77

Glycine levels and receptor binding were measured in the medulla and spinal cord of 2-month, 10-month, and 24-month-old Fischer 344 rats. The behavioral response to the administration of the glycine antagonist, strychnine, was also evaluated in 2- and 24-month-old animals to investigate the relevance of these parameters to the susceptibility to seizures. Significant reductions in glycine in both the spinal cord and medulla occurred from 2 to 24 months of age. The glycine precursors, serine and threonine, were decreased only in the spinal cord. [3H]Strychnine binding was also decreased by 38% and 34% in the medulla and spinal cord, respectively, of 24-month-old rats compared to 2-month-olds. [3H]GABA binding was similarly reduced while no age-related changes in [3H]diazepam binding in the spinal cord were detected. Comparison of 2- and 24-month-old animals after systemic injection of 1.75 mg/kg strychnine showed that senescent animals have a higher incidence of seizures and mortality compared to young animals. Decreases in glycinergic neurotransmission may lower strychnine seizure threshold in the aged animal.
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PMID:Age-dependent changes in brain glycine concentration and strychnine-induced seizures in the rat. 270 86

Agonist, and antagonist effects of the proposed kappa opioid agonist, U50,488H (U50) have been studied in an experimental model of seizure activity (flurothyl-induced seizure threshold) (ST) and in the central modulation of spontaneous, volume-induced micturition contractions (bladder motility) (BM) in rats. Intracerebroventricular (i.c.v.) administration of U50 (at the doses tested) did not produce any agonist effect in either ST or in BM. In contrast, i.c.v. administration of [D-Ala2, NMPhe4, Gly-ol]enkephalin (DAGO) or etorphine, agonists with activity at mu opioid receptors, produced an elevation of ST and inhibition of BM. The elevation in ST produced by etorphine (0.004 nmol) was prevented by prior treatment with U50. In contrast, the approximately equieffective elevation in ST resulting from DAGO was not affected by U50 pretreatment. Similarly, pretreatment of rats with U50 antagonized the approximately equieffective BM effects of etorphine, but not those of DAGO. As both DAGO and etorphine are thought to exert their effects via the opiate mu receptor, the results may be consistent with the view that subpopulations of mu receptors exist within the central nervous system; these sites may be differentially associated with the kappa receptor.
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PMID:Differential antagonism of mu agonists by U50,488H in the rat. 282 58


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