Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0494475 (tonic-clonic seizure)
 1,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebrospinal fluid gamma-aminobutyric acid (CSF GABA) was analyzed in 151 patients who underwent evaluation for central nervous system disease. CSF GABA was not detected in 19 of these patients, who had no evidence of neurologic disease and who served as controls. GABA was most frequently detected in patients with cerebrovascular disease, and was detected only in Parkinson's syndrome of atherosclerotic origin and dementia of multi-infarct type. CSF GABA was not detected in Alzheimer's disease or Huntington's disease. Patients with grand mal seizures exhibited CSF GABA elevation within 24 hours of the ictus. In patients with multiple sclerosis GABA detection was related to the presence or exacerbation of spinal cord lesions. Further study is necessary to evaluate the significance of elevated CSF GABA in central nervous system disease.
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PMID:Cerebrospinal fluid gamma-aminobutyric acid in neurologic disease. 13 99

The action of intravenously injected taurine, glycine and GABA has been tested on convulsions induced by strychnine using electroencephalographic and electromyographic recordings. The dose of strychnine necessary to produce a generalized tonic-clonic seizure was 0.55 +/- 0.15 mg/kg intravenously for rabbits pretreated with taurine, which was significantly higher than for control animals (0.38 +/- 0.13 mg/kg). After pretreatment with glycine, the strychnine dose required to evoke convulsions (0.51 +/- 0.22 mg/kg) was also higher than the control values, but the difference was statistically not significant. The convulsive dose of strychnine in animals pretreated with GABA was slightly but not significantly lower than in control animals (0.31 +/- 0.13 mg/kg). These results suggest that taurine is the most effective amino acid to protect rabbits from seizures induced by strychnine.
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PMID:Effects of taurine, glycine and GABA on convulsions produced by strychnine in the rabbit. 43 61

An anticonvulsant action of ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist (5-40 mg/kg IP), on the bicuculline-induced (3-8 mg/kg IP) or picrotoxin-induced seizures (3-6 mg/kg IP) was assessed in male Wistar rats aged 7, 12, 18, 25 and 90 days. Ketamine alone caused moderate ataxia which was more pronounced in younger animals. In combination with both aforementioned convulsants, ketamine exerted anticonvulsant effects against generalized tonic-clonic seizures in all developmental stages studied. This effect was more pronounced in bicuculline-treated animals. Moreover, ketamine also suppressed the lethality induced by both drugs during all the development. On the contrary, the action of ketamine on minimal (clonic) seizures was moderate or absent. Our results suggest an important role of ketamine-affected transmission in the generation of the generalized tonic-clonic seizure pattern; moreover, an action of high doses of ketamine on GABA-A receptors might be present.
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PMID:Ketamine suppresses both bicuculline- and picrotoxin-induced generalized tonic-clonic seizures during ontogenesis. 209 70

The anticonvulsant effects of two doses of clonazepam (CZP, Rivotril Roche, 0.1 and 1 mg/kg i.p.) were studied on model motor seizures induced by strychnine, bicuculline, 3-mercaptopropionic acid and metrazol in male laboratory rats (Wistar strain). In the first part the effects of different doses of the convulsants were investigated and for interaction with CZP doses were chosen after which more than 70% of the animals displayed generalized tonic-clonic convulsions (a grand mal seizure). Strychnine induced this type of seizure only: two doses (2 and 3 mg/kg s.c.) were used. CZP reduced the incidence of convulsions only after the larger dose, but plain solvent (propylene glycol, ethanol, water) was equally effective. The other substances first induced a seizure of minimal (mainly clonic) convulsions and only later a grand mal seizure. CZP was highly effective against bicuculline (3 mg/kg s.c.) and metrazol (100 mg/kg s.c.), but was less so against 3-mercaptopropionic acid. The effect on grand mal seizures was more pronounced in every case than on minimal seizures. The decisive role in the anticonvulsant effect of CZP is played by the mechanisms by which the convulsants induce epileptic manifestations. CZP is most effective against substances acting on the supramolecular complex GABA receptor (benzodiazepine receptor) chloride ionophore (bicuculline and probably metrazol).
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PMID:Anticonvulsant effects of clonazepam on chemically induced convulsions. 215 Sep 91

The peripheral BDZ receptor ligand Ro 5-4864 was administered to rabbits in doses ranging from 0.2 to 7 mg/kg IV. Changes in electrocortical activity appeared within 1 min after administration, characterized by trains of slow waves in the posterior sensorimotor and optic cortices (0.6-2 mg/kg) and by grand mal seizures (2-10 mg/kg). The low doses also induced alterations in the basic rhythms both of the hippocampus (reduced amplitude and spike-like waves) and of the nucleus ventralis of thalamus (trains of slow waves), not associated with observable behavioural changes. The paroxysmal EEG activity observed at higher doses of the drug was first recorded in the cortical areas and then spread to the subcortical structures. No change in electrical activity could be observed in the spinal cord. The paroxysmal activity was associated with tonic-clonic convulsions and scialorrea. The EEG and behavioural manifestations were inhibited by administration of Ro 15-1788. This drug at doses of 0.6 and 6 mg/kg antagonized the effects of Ro 5-4864 at doses of 0.6-5 mg/kg and 6-7 mg/kg, respectively. This effect began 1-3 min after administration of the antagonist, and led to EEG synchronization. These data suggest that in rabbits the convulsant effect of Ro 5-4864 is due to interference of the drug at the GABA-BDZ-picrotoxin receptor oligomeric complex. Such an effect seems to be mediated at least in part by central BDZ receptors.
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PMID:The peripheral benzodiazepine receptor ligand Ro 5-4864 induces supraspinal convulsions in rabbits. Reversal by the central benzodiazepine antagonist Ro 15-1788. 300 10

Animal models of epilepsy are essential for the search of new effective antiepileptic drugs. Moreover they may lead to the discovery of the basic neuronal dysfunction(s) which underlies human epilepsies. Animal epilepsies as well as experimental seizures are usually considered as valid models of human epilepsies when, and only when, the drugs which are effective in human epilepsies prevent seizures in animals. This, however, precludes finding new drugs for resistant epilepsies. Animal models of epilepsy can be classified as follows: (i) experimental seizures induced by convulsant drugs or by an electrical stimulation; (ii) reflex epilepsies; (iii) idiopathic epilepsies. Examples of animal models of epilepsy taken from each of these three classes are briefly reviewed. Seizures induced by convulsant drugs or by an electroshock are widely used as simple and rapid screening systems for new anticonvulsant compounds. Moreover, the use of chemical convulsants can lead to new hypotheses concerning the mechanisms underlying human epilepsies. Thus, one of the main arguments in favor of the GABAergic hypothesis of epilepsy is that GABA antagonists induce seizures which are readily counteracted by most antiepileptic drugs. Among the other models of experimentally induced seizures, the kindling model is usually considered, on the basis of its pharmacological characteristics, as a Grand Mal type epilepsy model. Thirty years after this model was first described, the exact modifications induced in the brain by the kindling procedure remain unknown. Various animal species exhibit reflex epilepsies. Myoclonic seizures can be induced by photic stimulation in Papio-papio baboons; tonic-clonic seizures can be induced by various auditory stimuli in certain strains of mice and rats; myoclonic and tonic-clonic seizures can be induced by a variety of environmental stimuli in the mongolian gerbil; photosensitive and febrile seizures have been described in fowl. Most antiepileptic drugs are effective in these reflex epilepsies. Alterations in several neurotransmitter systems have been reported in susceptible strains as compared to resistant strains, such as modifications in noradrenergic, serotoninergic, GABAergic or glutamatergic transmissions, but no single abnormal parameter can unequivocally be correlated to seizure susceptibility. Idiopathic epilepsy is not uncommon in dogs and the prevalence of the disease appears to be comparable to that observed in man. Grand Mal type epilepsy appears to be the most frequent type of epilepsy in dogs; little work has been devoted to the study of the neurochemical alterations which may underly the disease.
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PMID:[Animal models of epilepsy and experimental seizures]. 311 33

The intrinsic processes involved in the initiation and arrest of seizures are not completely understood. Cortical and cerebellar inhibitory mechanisms, accumulation of metabolic products, and glial uptake of extracellular potassium (K+o), anions, and released neurotransmitters are all important processes that limit focal firing and terminate a seizure once it has been initiated. Of these, the intrinsic cortical inhibitory mechanisms--i.e., recurrent and surround inhibition--appear to be the most important. Active cation and anion transport processes are two metabolic events that have yet to be elucidated but clearly could be involved in terminating a seizure discharge. For example, without an active mechanism to transport chloride, opening of the chloride channel by the inhibitory transmitter GABA would not result in increased chloride permeability. The transient hypoxia and hypercapnia and lactic acidosis that follows a severe tonic-clonic seizure produces a mixed systemic metabolic and respiratory acidosis. In experimental animals, the hypercapnia that results is sufficient to block seizure discharges. Increasing the CO2 concentration significantly reduces the extension to flexion (E/F) ratio of mice given maximal electroshock seizures (MES) and increases the time required for 50% of the animals to recover sufficiently from a first MES to be able to have another MES. The decreased E/F ratio and the increased recovery time (RT50) are both indicative of a decrease in seizure activity. Since the extent to which CO2 is allowed to accumulate in the brain is regulated by the glial specific enzyme carbonic anhydrase (CA), it follows that the glial cell has an integral role in the mechanisms involved in arresting seizure activity. In contrast, hypoxia increased the E/F ratio and decreased the RT50, evidence that seizure activity was enhanced. Another metabolic factor affecting duration of seizure activity, susceptibility to seizures, and recovery from seizures is glucose. Recovery from seizures depends in part on an adequate supply of this energy source. An inverse correlation (R = 0.95) between RT50 and blood sugar was found when the blood sugar was altered experimentally by treatments that altered the endocrine status (pancreatectomy, treatment with alloxan, cortisol, insulin, glucagon, and dextrose). Since glial cells contain (as glycogen) the small amount of glucose present in the brain, they probably hasten the ability of the brain to recover normal function following a seizure.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of glial cation and anion transport mechanisms in etiology and arrest of seizures. 370 23

Bicyclic phosphorus esters (BCP) originating from the combustion of fire-retardant polyurethane foam containing phosphorus are highly toxic compounds and potent antagonists of GABA-ergic receptors. The clinical symptoms of the poisoning are grand mal seizures. The results of experiments on rats demonstrated that diazepam and phenobarbital reduce acute toxicity of the isopropyl-BCP-derivative and remarkably smooth poisoning symptoms.
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PMID:[Effect of diazepam and phenobarbital on the acute toxicity of bicyclic organophosphorus esters]. 377 96

The in vitro effects of the major non-benzodiazepine anticonvulsants were studied upon potassium-stimulated release of radiolabelled GABA and D-aspartate from minislices of rat cerebral cortex. At 100 mumol/l, some anticonvulsants effective in grand mal seizures (phenytoin, phenobarbitone, mephobarbitone and beclamide) selectively inhibited K+-evoked release of the excitant amino acid D-aspartate, consistent with an anticonvulsant action. In contrast, several other anticonvulsants, namely ethosuximide, methsuximide, carbamazepine, sulthiame and dipropylacetate failed to alter potassium-evoked release of either amino acid. The ionic basis of phenytoin action on release was further studied; interactions with both neuronal calcium and sodium ion channels appear necessary for the drug's inhibitory action.
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PMID:Inhibition of amino acid transmitter release from rat brain slices by phenytoin and related anticonvulsants. 613 93

The degenerative type of progressive myoclonus epilepsy (PME) is a hereditary disease with grand mal seizures, stimulus sensitive myoclonus, characteristic EEG and mental deterioration in the late stage. GABAergic antiepileptic drugs are the most effective ones in this disease, with an unknown etiology. In this study, the GABA concentration in the CSF of 15 PME patients was measured and compared with values of sex- and age-matched epileptic controls. It was correlated with the concentrations of 5HIAA and HVA in the CSF, which were determined earlier from the same patients. The GABA concentration in the PME patients was statistically significantly decreased, to about 75% of that of the epileptic controls. It correlated with HVA and 5HIAA concentrations in the PME patients, but not in the epileptic controls. It is unknown whether these findings are related to the primary cause of PME or whether they are only secondary, owing to a loss of respective neurons or synapses.
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PMID:Decrease of GABA in the cerebrospinal fluid of patients with progressive myoclonus epilepsy and its correlation with the decrease of 5HIAA and HVA. 618 74


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