Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of benzodiazepine sensitivity testing in the management of 40 children with intractable seizure disorders was studied. The aetiology and clinical syndromes varied widely with myoclonic, atonic and complex absence seizures predominating. Twenty-five cases had mixed seizure disorders. There was, likewise, a wide range of EEG abnormalities. Seven cases were in non-convulsive status at the time of testing. Diazepam (0.2 mg/kg) was given slowly intravenously and its effect on the EEG was observed. In 21 cases epileptiform activity was abolished. No change was seen in 13 cases and an unusual result was seen in 3. There was a paradoxical response in 3 cases, two of these associated with clinical seizures. Only 1 child in non-convulsive status had a positive result. Following testing, 32 patients went on to long-term oral benzodiazepine treatment. Twenty-one of these patients showed subsequent clinical improvement and 16/21 (76%) had had a positive sensitivity test previously. Eleven of these patients did not improve on long-term treatment. Seven out of the 11 (64%) had had a negative sensitivity test. These results suggest that the benzodiazepine sensitivity test is of value in the long-term management of intractable seizure disorders in childhood, but also emphasise the variability and unpredictability of response to benzodiazepine treatment.
 ...
PMID:Benzodiazepine sensitivity testing in the management of intractable seizure disorders in childhood. 244 52

Because hypothermia and anorexia were previously found to be more sensitive indices of the effects of lindane than were convulsions, these endpoints were used to quantify the ability of benzodiazepines (BDs) and phenytoin either to ameliorate or exacerbate the toxicity of lindane in the rat. After administration of lindane (40 or 50 mg/kg) in oil per os, toxicity was counteracted by phenytoin and the "central" BD agonists diazepam and clonazepam, but was worsened by Ro 5-4864 a "peripheral" BD agonist. Clonazepam and diazepam were each more effective in counteracting lindane-induced anorexia than in stimulating food intake, presumably because the animals had been fasted and probably even controls ate maximally when food was presented. Diazepam alone (3 injections in 1 day) produced withdrawal-induced decreased food intake the following day. Clonazepam and diazepam alone each transiently decreased colonic temperature, yet effectively blocked the more severe hypothermia produced by lindane. Ro 5-4864 by itself did not produce any measurable effects, yet exacerbated all of the effects, including lethal effects, of lindane. The present findings are compatible with other evidence that lindane and Ro 5-4864 act at the picrotoxinin receptor of the GABAA-activated chloride channel and that systemic administration of agents acting at this site may produce a constellation of effects, including seizures, hypothermia and anorexia.
 ...
PMID:"Central" and "peripheral" benzodiazepines and kinetics of lindane-induced toxicity. 247 Dec 14

Chronic treatment with benzodiazepine receptor agonists increases sensitivity to the convulsant action of FG 7142, an inverse agonist. We investigated whether or not changes in the number and function of GABA-gated chloride channels accompanies this increased sensitivity. Diazepam, 5 mg.kg-1, was administered to mice daily for five days, and mice were then tested with a single injection of FG 7142, 40 mg.kg-1, at several intervals thereafter. At 24 hours after the last diazepam dose, 10 of 15 mice had clonic seizures following FG 7142 and four of the remaining five had myoclonic jerks. At 48 hours, only one of six mice developed a clonic seizure, and none were observed in mice tested at 96 or 144 hours. Muscimol-stimulated chloride flux was reduced in cortical synaptosomes from diazepam-treated mice at 24 hours but not at 48 or 96 hours. However, the binding of [35S]TBPS, a ligand closely associated with the chloride channel, was unchanged at 24 hours. These results suggest that a transient diminution in GABA-gated chloride channel function; unaccompanied by a reduction in channel number, may underlie the sensitization to the convulsant action of FG 7142 observed after withdrawal from chronic diazepam treatment.
 ...
PMID:Diazepam sensitizes mice to FG 7142 and reduces muscimol-stimulated 36Cl- flux. 247 37

The muscle relaxant activities of orphenadrine (Norflex) and diazepam (Valium) were compared in several animal models. In mice, tonic extensor seizures evoked by electroshock or pentylenetetrazol were inhibited by both agents. The protective index (ataxic dose divided by protective dose) was greater than 1 for orphenadrine, whereas for diazepam it was greater than 1 only in the case of the pentylenetetrazol-induced seizures. In strychnine-treated mice, diazepam protected against deaths following tonic extensor seizures, but orphenadrine did not. The protective index for diazepam, however, was less than 1. In cats, orphenadrine and diazepam both were capable of blocking decerebrate ridigity, but not in all animals. The protective index for orphenadrine in animals in which it was active, was greater than 1, while that for diazepam, when it was active, was less than 1. Orphenadrine and diazepam were tested in rabbits in the sciatic nerve-gastrocnemius muscle preparation. Neither drug directly affected nerve muscle stimulation. It would appear that both agents are acting via the central nervous system when they suppress hypertonic skeletal muscle activity, but only orphenadrine exhibits protective indices consistently greater than 1.
 ...
PMID:Comparison of depressant actions of orphenadrine and diazepam on hypertonic skeletal muscle activity. 262 11

A 6-year-old girl with cerebral palsy developed conscious disturbance and generalized convulsion after one-hour hot herb drug bath. Physical examination on admission revealed rectal temperature 41 degrees C, hot skin, respiration 46/min, regular heart beat 98/min, BP 130/60 mmHg, Glascow coma scale 4 (E2M1V1), soft and flat abdomen, no hepatosplenomegaly, no skin rash, no focal neurological sign, increased generalized muscle ton. Laboratory data showed CBC: WBC 20400 cumm (Neutrophils 31%, Lymphocytes 69%), Hb 11.6gm%, ESR 11 mm/hr, arterial blood gas: PH 7.077, PO2 43mmHg, PCO2 57.1mmHg, HCO3- 16 mEq/L, BE-11.5mEq/L, serum sodium 143 mEq./L, potassium 5.2 mEq/L, chloride 101 mEq/L, free calcium ion 3.8mg%, GOT 63IU/L, GPT 263 IU/L, amylase 193 IU/L, alkaline phosphatase 388 IU/L, LDH 1245 IU/L, CPK 677 IU/L, total bilirubin 0.8 mg/dl, direct type 0.1 mg/dl, BUN 18 mg/dl, Glucose 35 mg/dl. Urinalysis revealed proteinuria( ) trace hematuria and pyuria, but no cast. Lumbar puncture is within normal limits. Bacteriology including blood and CSF are normal. Multiple organ failure was noted at that time. Intensive cooling methods were performed including central and peripheral cooling. We used luminal and valium to control the seizure. Condition didn't improve. Afterwards cardiopulmonary arrest developed. Patient expired 8 hours after admission despite of resuscitation. Heat stroke in infancy and childhood is different from that in adulthood. The predisposing factors are high ambient temperature, dehydration, very young baby, sweat gland dysfunction, or ectodermal dysplasia. Definition of heat stroke includes 1) rectal temperature above 41 degrees C, 2) behavioral change, 3) warm skin, wet or dry.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Status epilepticus induced by prolonged immersion in hot herb bath: report of one case]. 263 19

Anisodamine is a tropine alkaloid isolated from Scopolia tangutica Maxim. To determine the original sites of anisodamine seizure discharge, permanent electrodes were implanted into different parts of the brain in rabbits and the electrical activities were continuously recorded by monopolar leads. Injection of anisodamine 1.5 mg/kg into the lateral ventricle of conscious rabbits always produced abnormal discharges. The spike discharges appeared first in the amygdala and consisted of rhythmic large surface-positive spikes. Multiple spikes then appeared in the hippocampus, caudate nucleus, midbrain reticular formation and frontal cortex. Diazepam 1.5-2.5 mg/kg did not inhibit the spike discharges from the amygdala, but did inhibit the discharges from other sites as well as clonic convulsions. When the dosage of diazepam was increased to 4.5 mg/kg, the spike discharges from the amygdala were also inhibited. The above findings indicate that the site of origin of anisodamine seizure discharges in rabbits is the amygdala. The seizure discharges then spread to the mesencephalic reticular formation, the hippocampus, the caudate nucleus and the cortex. Diazepam was shown to be an effective antagonist against central stimulation induced by anisodamine.
 ...
PMID:[Sites of seizure discharges after intracerebroventricular injection of anisodamine and the antagonism by diazepam in rabbits]. 264 44

Benzodiazepines are potent and effective drugs for the management of acute seizures and status epilepticus. Lorazepam, diazepam, and clonazepam have been the most widely studied of the benzodiazepines in the treatment of status epilepticus. In 47 studies of these drugs involving 1,455 patients, lasting control of status epilepticus was achieved in 79% of the patients. None of these benzodiazepines is clearly superior to another for the effective control of status epilepticus. Differences in pharmacokinetic parameters, therefore, will influence the choice of drug. All three benzodiazepines are lipid-soluble and enter the brain within seconds to minutes after intravenous administration. Diazepam, however, is very lipid-soluble and highly protein-bound and thus has a very large volume of distribution of unbound drug. As a result, the effective duration of action of diazepam in status epilepticus is only 20 to 30 min, whereas that of lorazepam, which has a much smaller volume of distribution of unbound drug, is at least several hours after a single intravenous injection. This allows the orderly administration of an antiepileptic drug for long-term seizure control after status epilepticus has been controlled. For this reason, lorazepam is preferable for the initial management of status epilepticus. Continuous intravenous infusion of diazepam has been used successfully in the management of some patients with status epilepticus refractory to initial treatment.
 ...
PMID:Pharmacokinetics and clinical use of benzodiazepines in the management of status epilepticus. 267 May 37

Attacks of sustained dystonic postures of limbs and trunk can be initiated by mild environmental stimuli in an inbred line of Syrian hamsters. The trait is determined by an autosomal simple recessive genetic mutation, originally designated by the gene symbol sz, because the abnormal movements were thought to represent epileptic seizures. The attacks, which can be reproducibly initiated by placing the sz mutant hamsters in a new environment, begin with rapid twitches of the vibrissae, flattened ears, and flattened posture of the trunk while walking, followed by facial contortions, rearing, and sustained posturing of trunk and limbs, often resulting in falling over to the side or backwards. In the final stage, the hamsters became immobile, which can last for hours. An increased tone of limbs and trunk muscles can be palpated during the attack. Electromyographical recordings in awake, unrestrained mutant hamsters showed that the onset of the attack coincided with continuous tonic muscle activity and phasic bursts, which were present even when the animals did not move. During the attack, the animals continue to react to external stimuli. Bilateral electroencephalographic (EEG) recordings before and during motor disturbances in sz mutant hamsters showed no abnormalities. The severity of the dystonic syndrome in hamsters is age dependent with a peak at about 30-40 days of age. A score system for grading type and severity of dystonic attack was developed for use in drug activity studies. The severity of the attack was reduced or attacks were completely prevented by diazepam (1-2.5 mg/kg i.p.) and valproic acid (100-400 mg/kg i.p.) in a dose-dependent fashion. The latency to dystonic movements was significantly increased by diazepam but markedly reduced by subconvulsive doses of pentylenetetrazol (40 mg/kg s.c.). Diazepam antagonized the latency-reducing action of pentylenetetrazol in the hamsters. The pathophysiology and pharmacological sensitivity of the dystonic attacks in these animals remain to be further clarified, but the data indicate that the sz mutant hamsters might represent an interesting genetic model for paroxysmal dystonia. In view of these data, we propose that the hamster mutation should be re-named dystonic and that the new gene symbol should be designated dtsz.
 ...
PMID:The sz mutant hamster: a genetic model of epilepsy or of paroxysmal dystonia? 277 93

The protective effect of various alpha 2 adrenoceptor agonists such as clonidine, guanfacine, B-HT 920 and ICI 106270 was investigated against Ro 5-4864-induced convulsions in mice and rats. Clonidine and ICI 106270 exhibited a profound anticonvulsant effect while equivalent doses of guanfacine and B-HT 920 were less effective. The anticonvulsant effect of clonidine and ICI 106270 was reversed by pretreatment with yohimbine or idazoxan, indicating the involvement of alpha 2 adrenoceptors in their protective effect. Diazepam, clonazepam, CL 218, 872 and pentobarbitone exhibited a different profile of protective action, as these agents protected the animals from apparent mortality as compared to clonidine and ICI 106270 which prolonged the latencies of jerk and convulsion. Modulatory effects of alpha 2 adrenoceptors in central GABA function and multiple sites for Ro 5-4864-induced seizures are explained.
 ...
PMID:Modulatory effect of alpha 2 adrenoceptor agonists on Ro 5-4864-induced convulsions in rats and mice. 281 22

Common antiepileptic drugs and agents affecting different neurotransmitter systems were studied against aminophylline (280 mg/kg i.p.)-induced convulsions in mice. All drugs and agents were administered i.p. Diazepam and phenobarbital antagonized the whole seizure pattern and the respective ED50 values for the clonic phase were 3.5 and 62 mg/kg. Valproate at 500 mg/kg protected fewer than 50% of mice against the clonic phase. The remaining antiepileptics (acetazolamide, up to 1,000 mg/kg; carbamazepine and diphenylhydantoin, up to 50 mg/kg; ethosuximide, 500 mg/kg and trimethadione, 400 mg/kg) were totally ineffective in this respect. Propranolol (up to 20 mg/kg), baclofen (20 mg/kg), gamma-hydroxybutyric acid (300 mg/kg), aminooxyacetic acid (20 mg/kg), clonidine (up to 0.2 mg/kg), ketamine (30 mg/kg), atropine (20 mg/kg), papaverine (50 mg/kg) and L-phenylisopropyladenosine (2 mg/kg) did not affect the clonic phase either. Only antagonists of N-methyl-D-aspartic acid excitation, 2-amino-5-phosphonopentanoic acid and 2-amino-7-phosphonoheptanoic acid afforded protection against aminophylline-induced clonic seizure activity. The results show that aminophylline convulsions are relatively resistant to antiepileptic drugs and suggest that antagonists of excitatory transmission are potential antiaminophylline drugs.
 ...
PMID:Inhibition of aminophylline-induced convulsions in mice by antiepileptic drugs and other agents. 283 Oct 68


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>