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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 stereoisomers of gamma-glutamylaminomethylsulphonic acid (GAMS) on convulsions produced by intracerebroventricular injections of excitatory amino acids were studied in mice. gamma-D-GAMS preferentially blocked myoclonic seizures induced by kainate and had less pronounced anticonvulsant effect against quisqualate, N-methyl-D-aspartate, quinolinate, D-homocysteine sulphinate and L-glutamate. gamma-L-GAMS displayed only a relatively weak protective effect against kainate- and, to some extent, quisqualate-induced seizures, with little or no effect on the convulsant properties of the other excitatory amino acids. These results indicate that the D configuration of the gamma-carbon atom of excitatory amino acid antagonists is preferred not only for NMDA receptor antagonism but for antagonism at non-NMDA receptors as well.
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PMID:Anticonvulsant action of stereoisomers of gamma-glutamylaminomethylsulphonic acid in mice. 299 Sep 54

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

GDEE, a specific but low-potency antagonist of the quisqualate or 'Type 2' excitatory amino acid receptor, blocks seizures induced by homocysteine and quisqualic acid. Deaminated analogues of GDEE were examined for anticonvulsant activity in mice, for the purpose of determining the structural properties of GDEE required for anticonvulsant activity. The deaminated derivative of GDEE, diethyl glutarate (5 carbon chain) inhibited homocysteine thiolactone (HTL)-induced seizures with an ED50 of 533 mg/kg. A similar compound with carbon chain length increased by two (diethyl pimelate; 7 carbons) was less effective. Decreases or further increases in carbon chain length resulted in a nearly complete loss of activity. Dimethyl glutarate (5 carbons) and dimethyl adipate (6 carbons) were similar to diethyl glutarate in potency, blocking HTL-induced seizures with ED50s of about 625 and 540 mg/kg, respectively. Diethyl ethylmalonate, diethyl maleate, and diethyl fumarate were much less effective. Diethyl glutarate, but not diethyl succinate (4 carbons), blocked seizures induced by intracerebral quisqualic acid. None of the agents tested blocked pentylenetetrazole-induced seizures. Thus a number of deaminated structural variants of GDEE have anticonvulsant activity equal to that of GDEE. The amino group of GDEE appears therefore to be irrelevant for its anticonvulsant effect.
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PMID:Anticonvulsant activity of deaminated analogues of glutamic acid diethyl ester (GDEE). 316 73

Secondarily generalized convulsive status epilepticus was induced by intraperitoneal (i.p.) injection of D,L-homocysteine thiolactone to rats with actively epileptogenic cobalt lesions in motor cortex. This induced focal motor seizures which secondarily generalized. Control animals not treated with antiepileptic drugs had a mean of 18.3 generalized convulsions over a mean period of 103.8 min. Electrographic patterns seen during status epilepticus are described and are very similar to those seen during human status epilepticus. Phenytoin, phenobarbital, diazepam and lorazepam were all effective in arresting the generalized seizures when given i.p. after the second such seizure. Efficacy was serum drug concentration dependent. Concentrations effective in arrest of generalized seizures in this model are similar to those reported to be effective in the treatment of human status epilepticus. Diazepam ED50s for control of generalized tonic-clonic seizures and for arrest of all seizure activity were determined.
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PMID:Experimental secondarily generalized convulsive status epilepticus induced by D,L-homocysteine thiolactone. 319 90

Convulsive dose 50s (CD50s) for various convulsive drugs and minimal and maximal electroshock seizure thresholds were determined in DBA and C57 mice. DBA mice had lower maximal electroshock seizure thresholds (MESTs, 15%) and CD50s for homocysteine thiolactone (HTL, 23%) and bicuculline (69%), and a higher CD50 for pentylenetetrazol (PTZ) at 3 weeks of age, the age of maximal audiogenic seizure (AGS) susceptibility. At 8 weeks, when DBA mice are not susceptible to AGSs, significant differences were a lower minimal electroshock seizure threshold (mEST, 37%) and maximal EST (MEST) (19%), lower CD50s for N-methyl-D-aspartate (NMDA) (39%), kainic acid (KA, 50%), HTL (32%), strychnine (37%), and a higher CD50 for nicotine (55%) in DBA mice. Based on these data it is suggested that pathways involving NMDA and KA receptors are responsible for increased susceptibility to seizure initiation (mEST), and are opposed by glycine pathways, and that opposing GABA and cholinergic systems at higher CNS levels are involved in seizure spread (AGSs and MEST) in these mice. Latency patterns indicate that nicotine, strychnine, PTZ and bicuculline have high blood-brain barrier (BBB) penetrability. Picrotoxin and the excitatory amino acid receptor agonists had longer latencies, suggesting low BBB penetrability. Age-related changes in latency, however, give evidence that difficulty in drug penetration of the BBB is not responsible for differences observed in CD50s between strains.
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PMID:Seizure susceptibility in DBA and C57 mice: the effects of various convulsants. 329 31

The effect of L-homocysteine and selected derivatives on the high-affinity uptake of the inhibitory neuroeffectors, GABA and taurine, was investigated in synaptosomes, and in cultured neurons and astrocytes. High-affinity uptake of taurine into synaptosomes was inhibited most effectively by L-homocysteine, DL-homocysteine and homocystine whereas neuronal uptake was unaffected by any of the compounds tested. The high affinity uptake of taurine into astrocytes was markedly inhibited by L-homocysteine, L-homocysteic acid and L-homocystine. High-affinity GABA uptake into astrocytes was notably inhibited by L-homocystine, none of the other compounds tested causing appreciable inhibition below a concentration of 5 mM. Neuronal and synaptosomal high-affinity uptake of GABA was not significantly affected by any of the test compounds at concentrations below 5 mM. The implication of these results to the study of the mechanism of homocysteine-induced seizures and their relevance to the genetic disorder homocystinuria is discussed.
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PMID:Effect of L-homocysteine and derivatives on the high-affinity uptake of taurine and GABA into synaptosomes and cultured neurons and astrocytes. 368 29

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

The ability of betaine to block homocysteine, pentylenetetrazol, and electroshock induced seizures in mice has previously been observed. In this study, betaine administered IP and intraventricularly to rats blocked pentylenetetrazol-induced seizures, but IP betaine did not block audiogenic seizures. Intraventricular betaine was about 1000-fold more potent than IP betaine in blocking PTZ-induced seizures. Glycine, a component of the betaine molecule, was ineffective. It is concluded that betaine has an appreciable but selective effect in controlling experimental seizures in rats. This effect is mediated directly by the brain, and is not due to metabolism of betaine to glycine.
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PMID:Effects of betaine on seizures in the rat. 399 72

Electrocorticographic and behavioral effects of parenteral injections of homocysteine in rats are described. Homocysteine activates experimental foci and produces focal seizures in experimental animals with pre-existing lesions. It produces generalized ECoG seizures and generalized convulsions in unlesioned animals in higher doses.
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PMID:Focal and generalized experimental seizures induced by homocysteine. 615 62

The effects of pyridoxal phosphate, pyridoxine and hydrazine were studied on homocysteine-induced seizures in mice. Both of the B6 vitamers significantly decreased the latency and increased the severity, lethality and duration of seizures induced by homocysteine. The B6 inhibitor hydrazine sulfate, which is normally a convulsant, prevented the tonic component of the convulsions and increased the latency to the clonic component. This experiment indicates that a vitamin B6 dependent step is critically involved in the metabolic changes which precede homocysteine seizures.
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PMID:Homocysteine induced convulsions: enhancement by vitamin B6 and inhibition by hydrazine. 626 Mar 8


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