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

Clonazepam is a new benzodiazepine anticonvulsant recently approved by the Food and Drug Administration for the treatment of typical absence, infantile myoclonic, atypical absence, myoclonic, and akinetic seizures. It is rapidly absorbed by the oral route and appears to pass quickly from blood to brain. Preliminary results indicate a biological half-life of 22 to 32 hours and a therapeutic serum concentration of 5 to 50 ng/ml. Many studies report tolerance to the anticonvulsant effects with chronic administration. Major side effects of the drug are drowsiness, ataxia, and behavior changes. They tend to be dose related, occur early in the course of therapy, and may subside with chronic administration. Accordingly, the dosage is begun at a low level and increased slowly.
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PMID:Clonazepam. A review of a new anticonvulsant drug. 81 97

A group of 27 patients with various types of epilepsy were selected for a 6-month double-blind crossover study to compare the anticonvulsant effect and toxicity of eterobarb and phenobarbital. No statistically significant differences in seizure frequency were found among the 21 patients who completed the 6-month trial, but three others, in whom status epilepticus developed during the crossover from eterobarb to phenobarbital, had to be removed from the trial. The study provided some indication that when eterobarb and phenobarbital were used in high dosage with corresponding high serum barbiturate levels (over 30 mug per milliliter), eterobarb had a superior therapeutic effect. Side effects from both drugs included tiredness, sleepiness, nystagmus, and infrequently ataxia, but serious systemic toxicity did not occur. This study showed that eterobarb is a safe and potent anticonvulsant comparable in efficacy to phenobarbital, and the superior results obtained in some patients with eterobarb therapy indicate that it is an effective alternative anticonvulsant.
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PMID:Eterobarb therapy in epilepsy. 82 67

Rats were treated by intragastric intubation of a 20% ethanol solution in doses of 9-15 g/kg in 3-5 fractions for 1-7 days. Both tolerance and physical dependence were demonstrated after this treatment with the maximum tolerable doses to only a few days. Tolerance was assessed by signs of severity of intoxication: coma, loss of righting reflex, ataxia-3, ataxia-2, ataxia-1, sedation, and neutrality. During withdrawal, as blood ethanol concentrations approached 100 mg/dl the ethanol dependence phase was characterized by the onset of signs and responses of progressive severity: hyperactivity, tremors, spastic rigidity, and spontaneous convulsive seizures. A significant degree of tolerance was demonstrated for all signs of intoxication after 4 days of treatment, but did not reach maximum level even after 7 days. The severity of the withdrawal reactions intensified progressively to a maximum intensity after 4 days of treatment when as many as 72% of animals exhibited severe withdrawal signs and reactions including convulsive seizures. These different time courses suggest that tolerance and physical dependence are mediated through different mechanisms.
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PMID:Temporal relationship of the induction of tolerance and physical dependence after continuous intoxication with maximum tolerable doses of ethanol in rats. 82 49

Whole head fractionated doses of 200 r and 150 r were initiated postnatally in five experimental age groups (birth, 1-week, 2-week, 3-week and 4-week) and continued over a period of 14 or 20 days to prevent reconstitution of the external granular layer. Animals irradiated at birth displayed minor deficits in behavior, which included ataxia, tremor, hypertonus and dysmetria, while animals irradiated at 1-week showed only mild symptoms of hypermetria. All other animals displayed no motor deficits. Animals irradiated at birth had smaller eyes and ears, a reduction in the size of the entire head and were susceptible to seizures. All animals were sacrified at 70 days of age. The cerebellum was found to be reduced in size and weight, the greatest deficit being seen in animals x-irradiated at the very early ages. Newborn condition animals were found to have large compliments of interneurons in the molecular layer, an established internal granular layer, and Purkinje cells were found to have a normal orientation, position, and to be unreduced in number or size. Total granule cell deficits were found to range from 83% at birth to 29% at four weeks. Quantitative changes for the molecular layer, internal granular layer, medullary layer, Purkinje cell to granule cell ratio, and granule cell density, all depicted the greatest changes in the newborn, 1-week and 2-week conditions. This experiment confirmed that the critical period in the development at which damage would result in behavioral abnormalities was from birth to five days, while for neuroanatomical abnormalities, this critical period was from birth to 18 days.
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PMID:Effects of low-level x-irradiation on cat cerebella at different postnatal intervals. I. Quantitative evaluation of morphological changes. 83 Jun 69

Similar movement disorders developed in two 8-year-old retarded children while they were receiving phenytoin. Seizures subsequent to a diphtheria-pertussis-tetanus immunization had developed in each child at 1 to 2 months of age. A static encephalopathy ensued, characterized by mental retardation, ataxia, spasticity, and a mixed seizure disorder. Intermittent dystonia and choreoathetosis developed insidiously while serum phenytoin concentrations were in the therapeutic range. Sustained dystonia and choreoatheosis developed 2 hours after an oral provocation with phenytoin. The baseline abnormalities on the electroencephalogram remained unchanged during the choreoathetosis. Recognizable metabolic abnormalities known to be associated with similar movement disorders were excluded. It was concluded from these studies that the movement disorder is secondary to phenytoin and can occur at therapeutic serum concentrations. Phenytoin is a central anticholinergic agent and a central stimulant of serotonin, and may induce movement disorders as a result of altering these neurotransmitters in the brain. The variable expression of these movement disorders may relate to the nature of the preexisting striatal insult.
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PMID:Phenytoin-induced dystonia and choreoathetosis in two retarded epileptic children. 94 1

Clonazepam or 5-(2-chlorphenyl)-1, 3-dihydro-7-nitro-2H-1,4benzodiazepin-2-one, is a close structural and pharmacological relative of nitrazepam. It has a broad spectrum of activity against the various types of epilepsy, and is effective in many patients whose condition has proved resistant to other antiepileptic drugs. Its chief uses are in status epilepticus, in which intravenous clonazepam may replace diazepam as the drug of first choice, and in the minor motor seizures of childhood, particularly petit mal absences, the Lennox-Gastaut syndrome and infantile spasms. Clonazepam is also at least as effective as current treatment in psychomotor and myoclonic epilepsies, but seems unlikely to replace phenytoin and the barbiturates in the treatment of grand mal or focal motor seizures except in patients resistant to standard therapy. Initial success with clonazepam can be followed by loss of effect, but benefit can often be restored, at least initially, by temporary interruption and re-institution of treatment. Side-effects are common with clonazepam. Most patients experience drowsiness and fatigue, which are frequent causes of withdrawal, together with lesser incidences of ataxia, dystonia, hypotonia, and hyperactivity. These effects usually disappear with continued therapy, and are minimised by gradual introduction of the drug over 2-4 weeks. Hypersalivation and excessive bronchial secretion may be a problem in children and infants.
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PMID:Clonazepam: a review of its pharmacological properties and therapeutic efficacy in epilepsy. 97 34

A family is described with essential non-progressive chorea occurring in an autosomal dominant inheritance pattern over four generations. A few families with an apparently similar disorder have been reported previously. This condition is characterized by early childhood onset of chorea which is not progressive and is compatible with a long life. It is not associated with dementia, seizures, rigidity, or ataxia. It is a socially embarrassing condition and may, sometimes, be associated with behavioural problems and learning difficulties. For genetic counselling, it is important to distinguish this disorder from Huntington's disease and other hereditary disorders associated with chorea.
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PMID:Familial essential ("benign") chorea. 100 46

Clonazepam, an antiepileptic benzodiazepine derivative was administered into 30 patients mainly with incurable type epilepsy. Results were as summarized below: (1) Clonazepam was effective in 44.4% of 36 cases of seizures. The initial effect was noticed in 55.6%. (2) Clonazepam was proved to have a broad spectrum in its efficacy. It showed the highest rate of effectiveness, 71.4%, on psychomotor seizures. (3) Clonazepam was effective in all 4 cases of the photogenic epilepsy which shows the photosensitivity in the EEG. With the exception of 1 case, the sensitivity in the EEG also disappeared responding to clonazepam. (4) The Jacksonian type of the partial motor seizure disappeared in 2 cases after the administration with clonazepam. (5) The effects of clonazepam of EEG were examined in 24 patients. The abnormality of the basic activity, the diffuse epileptic discharge and the focal epileptic discharge were improved in 29.2%, 61.5% and 66.7%, respectively. In addition, the rate of the clinical effectiveness was high in the cases with the centrencephalic discharge. (6) Side effects were observed to have appeared in 38.9% of the patients. They were mostly drowsiness and ataxia. (7) Based on the above-mentioned results, it can be claimed that clonazepam is effective on psychomotor seizures, photogenic epilepsy and the secondary type of generalized convulsion (Jacksonian).
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PMID:[Antiepileptic activity of clonazepam--an antiepileptic benzodiazepine derivative]. 103 51

The antagonism of various components of maximal Metrazol-seizures (MMS) (i.e. tonic hindpaw extension, tonic backward extension of the forepaws, generalized clonic seizures and tremors), ataxia and loss of righting reflex-activity have been studied in a standardized procedure comparing 41 antiepileptics and related compounds. Appropriate analyses (Cluster Analysis and Principal Component Analysis) resulted in the distinction of seven clusters which could be considered along two continua. A first continuum is characterized by a progressive strengthening of loss of righting reflex-inducing properties, a decreasing dissociation of ataxia and loss of righting reflex and the disappearance of a selective anticonvulsant effect. The second continuum is characterized by an increasing relative potency of ataxia-inducing properties, an increasing dissociation of ataxia and loss of righting reflex and a decreasing antagonism of tremors. Three main types of anticonvulsants could be defined: drugs with a complete anti-MMS effect antagonizing both clonic and tonic seizures; drugs selectively abolishing tonic seizures, i.e., tonic extension of hind- and forepaws; and drugs exclusively blocking tonic hind-paw extension. The neurological and clinical significance of these different types of anticonvulsant activity has been discussed. Finally, the described modification of the maximal Metrazol-seizures test is proposed for routine screening purposes.
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PMID:Antagonism of maximal metrazol seizures in rats and its relevance to an experimental classification of antiepileptic drugs. 103 60

Clonazepam, a chlorinated derivative of nitrazepam, was administered to 10 children with absence seizures. Serum concentrations were measured after 8 weeks of treatment, at steady state. Seizure frequency reports and the 12-hour telemetered electroencephalogram were studied before and after 8 weeks of treatment to determine the frequency and duration of generalized spike-wave paroxysms. The clonazepam dosage ranged from 0.028 to 0.111 mg per kilogram and was reflected in serum levels ranging from 13 to 72 ng per milliliter, with an excellent correlation between dose and serum level. Eight of the 10 patients showed a significant decrease in seizure frequency, with three experiencing no seizures at all. Six patients had side effects, predominantly drowsiness and ataxia. This preliminary study shows clonazepam to be useful in the treatment of absence seizures in children and to merit further study.
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PMID:Serum clonazepam concentrations in children with absence seizures. 108 13


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