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

1 Interactions of depressant and anticonvulsant drugs with the neuronal gamma-aminobutyric acid (GABA) receptor + effector system have been examined on afferent fibres to the rat cuneate nucleus in vitro. Three types of interaction have been measured: (a) potentiation of depolarizing responses to the GABA analogue, muscimol: (b) reduction in the potency of bicuculline as an antagonist of muscimol at the GABA receptor: (c) reduction in the potency of picrotoxin as an antagonist of muscimol acting on the effector mechanism. 2 Phenobarbitone reduced the potency of picrotoxin in doses which did not affect the potency of bicuculline and which caused only a small potentiation of muscimol. Pentobarbitone did not show such selectivity, a reduction in potency of picrotoxin always being accompanied by a reduction in potency of bicuculline and a substantial potentiation of muscimol. 3 Flurazepam and lorazepam both reduced the potency of picrotoxin without affecting that of bicuculline and with very little potentiation of muscimol. Phenytoin had no effect on the potency of picrotoxin whilst potentiating muscimol to the same extent as phenobarbitone. 4 The spectrum of drug activity in reducing the potency of picrotoxin correlates well with the reported anticonvulsant effects of these drugs against kindled amygdaloid seizures. Potentiation of muscimol and reduction of bicuculline potency appear more closely related to hypnotic properties.
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PMID:Distinction between the effects of barbiturates, benzodiazepines and phenytoin on responses to gamma-aminobutyric acid receptor activation and antagonism by bicuculline and picrotoxin. 626 19

Ro 5-4864 (4'-chlorodiazepam) elicited convulsions in mice with a CD50 of 23.5 mg/kg (i.p.) and increased the firing rate of substantia nigra zona reticulata neurons in a dose dependent fashion (0.5-4 mg/kg i.v.). Diazepam and clonazepam, but not Ro 15-1788, were potent inhibitors of Ro 5-4864 induced convulsions. Ro 15-1788 was also ineffective in reversing Ro 5-4864 induced increases in cell firing of zone reticulata neurons. Muscimol potently inhibited the seizures and reversed increases in cell firing elicited by Ro 5-4864. Phenobarbital and pentobarbital inhibited Ro 5-4864 induced convulsions with moderate potencies, while phenytoin and carbamazepine were ineffective at doses of up to 100 mg/kg. These observations suggest that Ro 5-4864 does not elicit its pharmacologic actions through a direct action at a 'brain-type' benzodiazepine receptor. However, both the profile and potency of compounds effective in inhibiting the electrophysiological and pharmacological effects of Ro 5-4864 suggest that this compound may act by perturbation of a component of the GABA-benzodiazepine receptor chloride ionophore complex. These findings do not, however, rule out a direct involvement of the high affinity 'peripheral-type' benzodiazepine receptors found in brain.
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PMID:Electrophysiological and pharmacological actions of the convulsant benzodiazepine Ro 5-4864. 632 93

Chronic oral phenobarbital treatment (50 mg/kg every 12 hr for 8 weeks), which was nontoxic and continuously protective against seizures in rats, significantly decreased folate concentration in liver (29%) but not in brain or plasma. The apparent activity of 5,10-methylenetetrahydrofolate reductase (MTR) in liver decreased with initiation of treatment but then increased with a significant correlation to the length of treatment. Phenobarbital also stimulated the activity of this enzyme slightly in vitro. Methionine adenosyltransferase (MAT) activity was inhibited by high concentrations of phenobarbital in vitro but was not affected in vivo. No significant effects of phenobarbital on the activities of serine hydroxymethyltransferase (SHMT) or 5-methyltetrahydrofolate:homocysteine methyltransferase (MHMT) were observed either in vivo or in vitro.
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PMID:Effect of chronic phenobarbital treatment on folates and one-carbon enzymes in the rat. 638 80

Epileptic seizures can be evoked in chicks homozygous for the epileptic seizure gene (epi, epi) by elevating their body temperature using microwave diathermy. These seizures precede and differ in motor seizure pattern from a second clonic-tonic seizure produced by hyperthermia in both epileptic and carrier (heterozygote, Epi, epi) chicks. Hyperthermia did not evoke seizures in adult epileptic chickens. Phenobarbital delayed the onset of epileptiform seizures whereas phenytoin and valproate had no effect. These data suggest that epileptic chicks may provide a suitable model for studies on febrile convulsions.
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PMID:Febrile seizures in epileptic chicks: the effects of phenobarbital, phenytoin and valproate. 640 41

The purpose of this study was to compare three different modes of treatment in the prevention of relapses of febrile convulsions (Phenobarbital = PH, Sodium Valproate = SV, Placebo = PO) in a randomized therapeutic trial. The patients included in the study had shown their first generalized convulsive seizure during a bout of fever (greater than or equal to 38.5 degrees C) and were aged between 6 months and 4 years. They were subsequently followed up as outpatients, and Phenobarbital and sodium valproate levels were measured regularly to ascertain compliance with the treatment and to adjust the dosage accordingly. The patients' families were questioned with respect to the occurrence of feverish bouts and convulsive seizures during the interval between visits, as well as possible adverse reactions. An EEG was carried out yearly. Results were as follows: - 69 patients - 35 boys and 34 girls - with an average age of 24 months were divided into 3 groups according to treatment: 21 cases on PH, 22 cases on SV, and 26 cases on PO. - they were followed up for an average duration of 21 months. - the average number of feverish bouts per child and per year was evaluated at 2.5, no statistically significant difference being noticeable between the various modes of prophylaxis. - 15 relapses of febrile seizures were noted in 14 children, over an average duration of 23 months; on average, relapses occurred after 9 months; among the 14 children who had relapsed, one had been treated with SV, 4 with PH and 9 with PO, leading to estimated relapse rates of 4%, 19%, and 35% respectively. There is a statistically significant difference in the relapse rates between the treated groups (SV and PH) and the Placebo group, and a particularly significant difference between Sodium Valproate and Placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevention of recurrent febrile convulsions--a randomized therapeutic assay: sodium valproate, phenobarbital and placebo. 642 41

A 2-year-old boy of above-average intelligence experienced seizures, manifested by ticlike turning movements of the head, which were induced consistently by his own singing--not by listening to or imagining music. His seizures were also induced by his recitation and by his use of silly or witty language such as punning. The neurologic examination showed only a right-sided Babinski's sign. Seizure activity on an EEG was present in both temporocentral regions, especially on the right side, and was correlated with clinical attacks. A computed tomographic scan was normal. Phenobarbital therapy did not reduce seizure frequency.
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PMID:Seizures induced by singing and recitation. A unique form of reflex epilepsy in childhood. 647 21

Pharmacokinetic characteristics of the anticonvulsant phenobarbital were studied in seven pony and two Thoroughbred foals aged between four and 10 days. A single, 20 mg/kg bodyweight (bwt) dose of phenobarbital was given intravenously over 25 mins and the serum concentrations of the drug were measured using an EMIT AED assay (coefficient of variation 1.37 per cent at 30 micrograms/ml, n = 7). Phenobarbital elimination was found to follow first order kinetics. The mean (+/- sd) peak phenobarbital serum concentration was 18.6 +/- 2.1 micrograms/ml at 1 h after initiation of infusion with a mean (+/- se) half-life of 12.8 +/- 2.1 h. The mean (+/- se) volume of distribution was 0.86 +/- 0.026 litres/kg bwt and mean (+/- se) total body clearance was 0.0564 +/- 0.0065 litres/kg bwt/h. Sedation was noticed 15 to 20 mins after the beginning of infusion and lasted for up to 8 h. All foals could be aroused and could walk although they were ataxic for the first 1 to 2 h. A degree of delayed hyperexcitability occurred 3 to 8 h after infusion. In equine neonatal seizure disorders it is recommended to use a loading dose of 20 mg/kg bwt of phenobarbital, followed by maintenance doses of 9 mg/kg bwt at 8 h. With this regimen, average steady state serum phenobarbital concentrations should range between approximately 11.6 and 53 micrograms/ml. Phenobarbital serum concentrations should be monitored following the loading dose and 24 h after initiating the maintenance doses to check that levels remain within the suggested (human) therapeutic range of 15 to 40 micrograms/ml.
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PMID:Preliminary study on the pharmacokinetics of phenobarbital in the neonatal foal. 647 36

A 2-year-old child with known neurologic impairment developed a dyskinesia soon after starting phenobarbital therapy for seizures. Known causes of movement disorders were eliminated after evaluation. On repeat challenge with phenobarbital, the dyskinesia recurred. Phenobarbital should be added to the list of anticonvulsant drugs that can cause movement disorders.
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PMID:Phenobarbital-induced dyskinesia in a neurologically-impaired child. 650 32

In more than 98% of randomly bred gerbils epileptic seizures could be evoked by blowing at the animals with compressed air (5 bars for 10 s). In contrast, only few animals showed seizures in response to environmental stimuli (e.g., new cage) and handling. Thus, administration of drugs was possible without precipitating seizures. The severity of the seizures was rated on a seven-point scale. Seizure severity increased with age and reached its maximum at about 7 months. Comparison of pharmacokinetics of common antiepileptic drugs showed that these drugs, except phenobarbital, were rapidly eliminated by the gerbil which, in this respect, resembled the mouse. For determination of anticonvulsant ED50S of antiepileptic drugs in gerbils there was differentiated between "minor" seizures (grade 1-2; myoclonic seizures) and "major" seizures (grade 3-5; generalized clonic-tonic seizures). Phenobarbital, phenytoin and carbamazepine were more potent against major seizures than against minor seizures, whereas the reverse situation was obtained with diazepam, valproic acid and ethosuximide. The relative activity of the different antiepileptic drugs against minor and major seizures in gerbils corresponded to the respective activity in traditional mouse models of petit mal and grand mal epilepsy. In further experiments, a series of GABAmimetic drugs was tested, namely, compounds that selectively increase gamma-aminobutyric acid (GABA)-mediated neuronal inhibition in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of anticonvulsant drugs in gerbils with reflex epilepsy. 654 23

The high seizure susceptibility in epileptic fowl is an autosomal recessive trait characterized in homozygotes by seizures that occur spontaneously and in response to photic stimulation or hyperthermia. Both of the latter stimuli can be used to evoke seizures in drug studies. Epileptic fowl have abnormal inter-ictal EEG activity. When exposed to photic stimulation spiking is apparent on the EEG at seizure onset. Phenobarbital, primidone, phenytoin, and valproic acid reduce seizure susceptibility at plasma concentrations approximating those used to control generalized and focal cortical tonic-clonic seizures in humans. Carbamazepine and the benzodiazepines also reduce seizure susceptibility. These data indicate that epileptic fowl provide a useful model for generalized and focal cortical tonic-clonic epilepsies. Ethosuximide was inactive in epileptic fowl. However, trimethadione had anticonvulsant activity indicating that this model is only relatively specific for the above seizure types. When seizures were evoked by hyperthermia phenobarbital but not phenytoin or valproate reduced seizure susceptibility. GABA (gamma-aminobutyric acid), AOAA (amino-oxyacetic acid) and THPO (4,5,6,7-tetrahydroisoxazolo[4,5-c] pyridin-3-ole, a glial specific inhibitor of GABA uptake) all have anticonvulsant activity against seizures evoked by photic stimulation in young chicks. These data indicate that this model may be particularly useful for studies of the anticonvulsant activity of compounds designed to enhance GABAergic transmission.
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PMID:Anticonvulsants in epileptic fowl. 654 9


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