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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

gamma-Hydroxybutyrate (GHB) produces a constellation of EEG and behavioral events that respond selectively to antiabsence antiepileptic drugs. The GHB-induced seizure was quantitated in the presence of three other absence seizure models: pentylenetetrazole, systemic penicillin, and the flash evoked afterdischarge (FEAD). Penicillin and pentylenetetrazole produced a significant prolongation of GHB-induced seizure in a dose-dependent fashion. This potentiation of GHB seizure was observed when these compounds were given either before administration of gamma-butyrolactone (GBL), the prodrug of GHB, or at the onset of GHB-induced seizure. Photic stimulation given in a manner to produce FEAD also resulted in a significant prolongation of GHB-induced seizure. All of these maneuvers lowered the threshold to GHB seizure, but none interfered with the brain kinetics of GHB in the animals treated with GBL. Ethosuximide pretreatment significantly shortened the GHB seizure and overcame the potentiating effect of penicillin and pentylenetetrazole in this model. These data confirm the GHB-treated animal as a model of generalized absence seizure. The GHB model meets appropriate criteria for an absence seizure model and compares favorably with other models of absence currently in use.
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PMID:gamma-Hydroxybutyrate model of generalized absence seizures: further characterization and comparison with other absence models. 339 Nov 42

Much longer trains of conditioning stimuli are required to elicit inhibition descending from the reticular formation than to elicit segmental inhibition in the trigeminal nucleus. In contrast, a single conditioning stimulus is the most effective in eliciting descending facilitation, while the test stimulus alone is most effective in eliciting segmental excitation. Ethosuximide (ESM) selectively depresses descending inhibition and to a lesser extent segmental inhibition. Thus, ESM only depresses pathways requiring repetitive stimulation, such as inhibitory pathways in the reticular formation. This action would account for ESM's specificity for absence seizures, which are probably due to paroxysmal activity in inhibitory pathways.
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PMID:Differential effect of ethosuximide and of electrical stimulation on inhibitory and excitatory mechanisms. 350 81

The relative ability of phenytoin, ethosuximide and valproate to prevent minimal (clonic) threshold, maximal (tonic extension of the hindlimbs) threshold and supramaximal (tonic extension of the hindlimbs) seizures elicited by electrical and chemical (Metrazol, bicuculline, and picrotoxin) stimulation was determined. Ethosuximide and valproate were effective against minimal (clonic) threshold seizures, whereas phenytoin was ineffective and even activated them. All three anticonvulsants were effective against maximal (tonic extension of the hindlimbs) threshold seizures. Phenytoin and valproate, but not ethosuximide, were effective against supramaximal (tonic extension of the hindlimbs) seizures. The results suggest that the specificity of experimental models of epilepsy used in the evaluation of potential antiepileptic drugs is primarily due to the intensity rather than the nature of the stimulus used or the kind of seizure component evoked. Models based only on maximal (tonic extension of the hindlimbs) threshold seizures may identify anticonvulsant activity, but do not differentiate between substances that prevent seizure spread and those that increase seizure threshold.
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PMID:Effect of stimulus intensity on the profile of anticonvulsant activity of phenytoin, ethosuximide and valproate. 391 74

One-third of Wistar rats bred in our laboratory present recurrent seizures whose EEG and clinical symptomatology resemble those of human petit mal. Bilateral cortical synchronous spike- and wave discharges (7-11 c/s; 200-600 microV, lasting 0.5 to 40 s) accompany behavioral arrest and are associated frequently with facial myoclonia. These seizures, observed as long as the animals survive, appear spontaneously and seem to be unrelated to surgical procedures. Antiepileptics in common clinical use were tested. Ethosuximide (greater than 12.5 mg/kg), diazepam (greater than 0.5 mg/kg), trimethadione and sodium valproate (greater than 50 mg/kg) suppressed these discharges in a dose related manner. Carbamazepine and phenytoin were ineffective or aggravated the seizures. Phenobarbital, effective at 2.5 to 10 mg/kg, was ineffective at 20 mg/kg. The similar effects of these antiepileptics on both the rats' seizures and human petit mal confirm the hypothesis that this phenomenon constitutes a valid pharmacological model of petit mal epilepsy. Its predictive value appears to be superior to that of other currently used models.
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PMID:Antiepileptic drug evaluation in a new animal model: spontaneous petit mal epilepsy in the rat. 392 81

Wistar rats from our laboratory spontaneously present frequent epileptic seizures whose clinical semeiology, EEG signs and pharmacological reactivity resemble absence seizures in humans. In these rats, GABAmimetics such as THIP enhance the duration of seizures in a dose-dependent fashion. In contrast to the action of these drugs, valproate sodium (VPA), which potentiates GABAergic transmission, abolishes the seizures. VPA injected in association with THIP completely loses its therapeutic effects; moreover, VPA potentiates the aggravating effects of THIP. Ethosuximide which does not interact with GABA, was still effective when given in association with THIP. These findings raise questions as to 1. the role of GABAergic neurotransmission in the occurrence of spontaneous petit-mal-like seizures in the rat, and 2. the mode of action of antiepileptics against these seizures.
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PMID:Blockade of "antiabsence" activity of sodium valproate by THIP in rats with petit mal-like seizures. Comparison with ethosuximide. 393 Jun 59

We have assessed the relative neurochemical effects of valproic acid, ethosuximide, and diazepam on dissociated cultures of mouse cerebral cortex. Cultures were exposed chronically (11 days) to each antiepileptic drug and assayed for number of neurons, total protein, tetanus toxin fixation, high-affinity uptake of gamma-aminobutyric acid and beta-alanine, choline acetyltransferase activity, and specific and clonazepam-displaceable benzodiazepine binding. Ethosuximide-exposed cultures did not evidence neuronal toxicity; exposure to valproic acid and diazepam resulted in modest neuronal toxicity. However, exposure to each of these drugs resulted in a marked reduction in benzodiazepine binding. This effect may relate to a common mechanism of action of drugs used to treat absence seizures.
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PMID:Differential neurochemical effects of chronic exposure of cerebral cortical cell culture to valproic acid, diazepam, or ethosuximide. 393 44

The influences of delta 9-tetrahydrocannabinol (THC) and cannabidiol on electrically evoked cortical potentials of conscious rats with chronically implanted electrodes were investigated. Specifically, the cannabinoids' effects on a transcallosal evoked response were compared with those of ethosuximide, phenytoin, and pentylenetetrazol. THC produced dose-related opposite effects: Low doses increased the amplitude of the response, whereas higher doses reduced the response. Other drugs that can cause or exacerbate seizures, i. e., phenytoin and pentylenetetrazol, also increased the amplitude of the cortical response. In contrast, cannabidiol, over a wide dosage range, caused only depression. Ethosuximide, like cannabidiol, elicited a depressant effect. The data indicate that under the conditions of the present investigation, cannabidiol shares electrophysiological properties with ethosuximide but not with phenytoin, and that cannabidiol is a relatively selective, centrally acting drug. In addition, our findings support the suggestion that augmentation of neurotransmission in central pathways may contribute to the convulsant actions of THC, and the cannabinoids' depressant effects may, at least partially, account for their anticonvulsant actions.
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PMID:Excitatory and depressant effects of delta 9-tetrahydrocannabinol and cannabidiol on cortical evoked responses in the conscious rat. 627 47

Homozygous tottering mice (tg, autosomal recessive) exhibit frequent spontaneous "absence" seizures accompanied by bilaterally synchronous spike-and-wave or polyspike electrocorticographic discharges. In adult tottering mice, the antiepileptic effects of a single dose of ethosuximide, diazepam, phenobarbital, or phenytoin were assessed using continuous electrocorticographic recording to monitor seizure incidence. The dose chosen for each drug was selected to correspond to an effective antiepileptic dose in standard murine models. Ethosuximide, 150 mg/kg, diazepam, 1.4 mg/kg, and phenobarbital, 25 mg/kg were effective against absence seizures. In contrast, phenytoin at 5, 10, 30, or 60 mg/kg produced no significant reduction in the incidence of absence seizures. These results suggest that absence seizures in the tottering mutant may represent a relatively specific pharmacological model for the identification of drugs effective for clinical absence epilepsy, and emphasize the potential value of this new model for the study of fundamental mechanisms of absence of epilepsy and the actions of antiepileptic drugs.
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PMID:Anticonvulsant sensitivity of absence seizures in the tottering mutant mouse. 640 28

17 patients out of a total of 93 treated for primarily pure absence-epilepsy experienced secondary grand mal-seizures and eeg of 8 patients showed a grand mal-disposition (irregular s-w). These 25 patients, compared with the remaining 68 patients, attended more frequently a special school for mentally retarded children, their marks were worse, they left school in a lower form, and their vocational education was less qualified. 8 patients out of 65, who were primarily treated with Suxilep and without additional grand mal-remedy, experienced secondary grand mal-seizures (relative frequency 0.12). The question of the necessity of primary grand mal-prophylaxis is beeing discussed.
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PMID:[Prognosis in primarily pure absence epilepsy]. 640 59

Eliminating seizures should be the first goal of therapy for nonconvulsive epilepsies, but preventing seizures, i.e., guarding against head injuries and immunizing against agents that attack the nervous system, is the second goal. An accurate diagnosis of seizure type helps ensure that the appropriate medication for that particular form of epilepsy will be prescribed. Drug decisions should also be based on the risk: benefit ratio to the individual patient, and drug interactions should be considered when more than one drug is required. Frequent monitoring of drug serum levels is necessary in the case of multiple drug therapy or until seizures are controlled. Ethosuximide is considered the drug of choice in absence seizures, but valproic acid is equally effective. Although effective in controlling absence seizures, clonazepam is not favored in this indication because of a high incidence of side effects and the development of tolerance. Atonic seizures are generally refractory to treatment, but valproate, clonazepam, and occasionally carbamazepine represent the drugs of choice in management. Phenytoin continues to be a very popular drug for most types of seizures, but carbamazepine, used adjunctively until recently, is effective as monotherapy for the control of partial seizures, particularly those of the complex partial variety.
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PMID:Treatment of the nonconvulsive epilepsies. 641 1


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