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)

A 13 1/2-year-old child died with vitamin B6-dependent seizures in progress. Microscopic findings in brain included an abnormally sparse quantity of central myelinated fibers in the cerebral hemispheres. Glutamic acid concentrations were elevated and GABA concentrations reduced in the frontal and occipital cortices but not in the spinal cord. All other amino acid concentrations were normal, except for increased cystathionine in the occipital cortex. Pyridoxal-5-phosphate (PLP) was reduced in the frontal cortex. Glutamic acid decarboxylase activity comparable to that of controls was detected when the PLP concentration was greater than 0.05 mM. These findings suggest that pyridoxine-dependent seizures in man are associated with reduced GABA concentrations in the brain and with diminished central white matter structures.
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PMID:Vitamin B6-dependent seizures: pathology and chemical findings in brain. 56 38

Glutamic acid di-tert butyl ester (GTBE) was found to have a pronounced convulsant effect in mice and rats, producing recurrent clonic convulsions combined with postural and respiratory disturbances in a dosage of 0.5 mmol/kg (148 mg/kg). Tert-butyl ester derivatives of aspartic acid and alanine, and glutamic acid gamma-benzyl ester did not produce seizures. Various other glutamate esters, such as glutamic acid diethyl ester and glutamic acid dimethyl ester, have previously been found to have anticonvulsant effects, and also do not induce seizures. It is suggested that glutamic acid di-tert butyl ester may have specific pharmacological properties which differ from those of other known convulsant drugs.
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PMID:Convulsant properties of L-glutamic acid di-tert butyl ester. 286 66

alpha-Guanidinoglutaric acid (alpha-GGA) has been reported to occur in the cerebral cortex after epileptic seizures. No physical characteristics of alpha-GGA have been given. A practical procedure for the preparation of alpha-GGA is reported here. alpha-GGA forms a lactam in aqueous solution at 80 degrees C. It is proposed to substitute this lactam, 1-amidino-2-pyrrolidone-5-carboxylic acid (pAGlu), for pyroglutamic acid (pGlu) at the N-terminal position in neuropeptides to modify their biological characteristics. L(+)-Glutamic acid was reacted with S-methylisothiourea (I) at pH 10 in aqueous solution to form L(-)-alpha-guanidinoglutaric acid: mp 165-168 degrees C, [alpha]22D = -22.7 (C = 4, 2 M HCl). alpha-GGA reacted promptly with excess reagent to form a salt, S-methylisothiourea-alpha-guanidinoglutarate: mp 209-210 degrees C, [alpha]22D = -13.0 (C = 4, 2 M HCl). I was removed from the salt with aqueous picric acid, since I readily formed an insoluble picrate, S-methylisothiourea picrate (mp 225-228 degrees C). Alternatively, the salt was added to a cation exchange column, and the alpha-GGA was eluted with molar ammonium acetate buffer, pH 9.5. Its lactam, 1-amidino-2-pyrrolidone-5-carboxylic acid, mp 248-249 degrees C, [alpha]22D = +2.1 (C = 4, 2 M HCl), formed a picrate (mp 196-199 degrees C).
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PMID:The lactam of alpha-guanidinoglutaric acid (1-amidino-2-pyrrolidone-5-carboxylic acid). 287 49

[3H]Glutamic acid binding to hippocampi was increased after amygdaloid kindling in rats, and diazepam inhibited this increased binding, without any effect on the enhanced binding by CaCl2 or the binding in control rats. By inducing kindling in the same way as that used in the binding experiment, the inhibiting effects of diazepam on kindled seizures, the afterdischarge and the development of kindling were observed.
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PMID:Diazepam restores the increased [3H]glutamate binding to hippocampal synaptic membranes in the amygdaloid-kindled rat. 288 20

Glutamic acid diethyl ester (GDEE) is a glutamate antagonist which acts preferentially at the quisqualate-sensitive receptor and has been shown to be an effective anticonvulsant in alcohol withdrawal and homocysteine-induced seizures but ineffective in other seizure models. To better characterize the role of the quisqualate-sensitive receptor in the generation of seizures, quisqualate was administered to mice by intracerebroventricular (ICV) route and immediate onset generalized seizures were observed. The anticonvulsant properties of GDEE and commonly used antiepileptic drugs (AEDs) were investigated with this seizure model. GDEE given by intraperitoneal blocked quisqualate-induced seizures dose-dependently. Diphenyl-hydantoin (50 mg/kg IP), carbamazepine (50 mg/kg IP), diazepam (1; 4 mg/kg IP), phenobarbital (40; 80 mg/kg IP), and valproic acid (250; 340 mg/kg IP) were also administered prior to quisqualate-seizure induction. Only valproic acid blocked seizures at nonsedating doses. The GABA transaminase inhibitor aminooxyacetic acid (20 mg/kg IP) was ineffective, suggesting that here valproic acid is active at excitatory receptors rather than by potentiating GABA post-synaptic inhibition. These data are consistent with the hypothesis that the quisqualate-sensitive receptor is involved in some forms of clinically observed seizures, particularly those which are controlled by valproic acid.
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PMID:Inhibition of quisqualate-induced seizures by glutamic acid diethyl ester and anti-epileptic drugs. 310 Jul 18

The effect of chronic administration of gamma-vinyl GABA (GVG; vigabatrin) on levels of neurotransmission-related amino compounds was studied in lumbar cerebrospinal fluid of 65 patients with complex partial epilepsy. The first sample of cerebrospinal fluid was taken before a 3-month period of treatment with 3 g gamma-vinyl GABA/day, and the second was taken afterwards. From patients who showed a greater than 50% reduction in seizures (responders) or marked improvement in global performance, a third sample was taken at the end of the next 3-month phase, during which 3 g or 1.5 g gamma-vinyl GABA had been administered daily. During treatment with 3 g gamma-vinyl GABA/day, 55% of the patients showed more than 50% reduction in complex partial seizures; and at the same time free GABA, total GABA, homocarnosine, and glycine concentrations in the cerebrospinal fluid increased by 104%, 151%, 194% and 16%, respectively. After reduction of the daily dose to 1.5 g, the levels of free GABA, total GABA and homocarnosine were still increased by 65%, 115% and 102%, respectively. gamma-Vinyl GABA correlated with the levels of free GABA (P less than 0.002) and glycine (P less than 0.001). Concentrations of homocarnosine at baseline and homocarnosine and total GABA during gamma-vinyl GABA treatment were lower (P less than 0.005) in the group of non-responders than in the responder group. Glutamic acid, glutamine, aspartic acid, asparagine, and taurine levels did not change during gamma-vinyl GABA treatment. In conclusion, administration of gamma-vinyl GABA reduces epileptic seizures and produces dosage-dependent increases in levels of free GABA, GABA-containing peptides and of glycine in cerebrospinal fluid, without concomitant change in levels of excitatory amino acids.
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PMID:Inhibitory and excitatory amino acids in CSF of patients suffering from complex partial seizures during chronic treatment with gamma-vinyl GABA (vigabatrin). 314 62

Homocysteine thiolactone causes convulsions when administered to animals, and has recently been reported to have excitatory effects on neurons in the central nervous system. Glutamic acid diethyl ester (GDEE) has previously been found to be an effective antagonist of the central excitation induced by homocysteine and is thought to be a selective antagonist of the quisqualate-sensitive excitatory amino-acid-receptor site. If an interaction of homocysteine with the quisqualate-sensitive receptor site is responsible for its convulsive properties, GDEE might also block the induction of seizures by homocysteine. GDEE in a dosage of 4 mmol/kg almost completely blocked homocysteine-induced seizures in mice; smaller dosages had no effect or only slight inhibitory effects. Glutamic acid dimethyl ester (GDME) and glutamic acid gamma-methyl ester (GMME) also partially blocked homocysteine-induced seizures, but monosodium glutamate and glutamic acid gamma-monoethyl ester (GMEE) had only a slight effect. None of the glutamate esters inhibited seizures induced by pentylenetetrazole. It is therefore suggested that certain types of seizures involve the quisqualic acid excitatory amino-acid-receptor site. Homocysteine-induced seizures may serve as a model of seizures of this type, and GDEE, GDME, and GMME may be effective antagonists of such seizures.
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PMID:Selective inhibition of homocysteine-induced seizures by glutamic acid diethyl ester and other glutamate esters. 397 49

Glutamic acid microinjection into the rabbit dorsal hippocampus was studied in its effects on hippocampal and cortical electroencephalogram (EEG). The studies were carried out on rabbits with chronically implanted electrodes and cannulae. Bipolar, silver recording electrodes and stainless steel cannulae were implanted into the hippocampus, and recording electrodes were placed on the surface of the frontal and cingular cortical areas. Low doses of glutamic acid (5-25 nM) induced EEG and behavioral arousal. Short lasting epileptiform-like seizures and behavioral convulsions were induced after injection of high doses of glutamic acid (100-500 nM). These findings suggest that glutamic acid in the hippocampus of the rabbit is involved in behavioral arousal and epileptiform-like disorders.
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PMID:Excitatory effect of intrahippocampal injection of glutamic acid on rabbit EEG. 614 Dec 18

Glutamic acid has been believed to be an excitatory transmitter in the mammalian central nervous system (CNS), and has been implicated in the pathogenesis of neuronal damage in the mammalian CNS. There are two major classes of glutamate receptors, ionotropic (iGluR) and metabotropic glutamate receptors (mGluR). Participation of iGluRs in glutamate mediated neurotoxicity has been well documented. However, much less is known about participation of mGluRs than the case for iGluRs. The physiological roles of mGluRs have been believed to regulate transmitter release and to modulate the function of iGluRs through activating various intracellular second messenger system. Recently we have discovered several potent agonists for mGluRs which would provide additional information about glutamate mediated neurotoxicity. DCG-IV, one of the most potent mGluR agonists, alleviated kainate-induced limbic motor seizures in extremely low doses in the rat, but the dose response curves showed a bell typed one. DCG-IV also demonstrated severe sedative condition and markedly prolonged the sleeping time in halothane anesthesia. DCG-IV depressed the duration of after-discharges and the seizures evoked by electrical stimulation in the amygdala kindling rat. DCG-IV significantly decreased in number of kainate-induced degenerated neurons in the area of hippocampal CA1, amygdala and septum when DCG-IV was continuously applied into the ventricule. In conclusion, activation of mGluRs leads the alleviation of neuron damage induced by iGluR agonists.
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PMID:[Excitatory amino acids and neuronal death]. 772 52

Epilepsy is a common neurological disorder with seizures, but diagnostic approaches in veterinary clinics remain limited. Cerebrospinal fluid (CSF) is a body fluid used for diagnosis in veterinary medicine. In this study, we explored canine epilepsy diagnostic biomarkers using gas chromatography-mass spectrometry (GC-MS)-based metabolic profiling of CSF and multivariate data analysis. Profiles for subjects with idiopathic epilepsy differed significantly from those of healthy controls and subjects with symptomatic epilepsy. Among 60 identified metabolites, the levels of 20 differed significantly among the three groups. Glutamic acid was significantly increased in idiopathic epilepsy, and some metabolites including ascorbic acid were changed in both forms of epilepsy. These findings show that metabolic profiles of CSF differ between idiopathic and symptomatic epilepsy and that metabolites including glutamic acid and ascorbic acid in CSF may be useful for diagnosis of canine epilepsy.
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PMID:Gas chromatography-mass spectrometry-based metabolic profiling of cerebrospinal fluid from epileptic dogs. 2433 64


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