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

Sodium dipropylacetate, an anticonvulsant used in human therapy, gives a more efficient protection against convulsions elicited by pentetrazol than by picrotoxin. In the case of picrotoxin induced convulsive seizures where there is an alteration at the GABA receptor level, ther is a lack of efficiency after nDPA treatment which increases GABA at the synaptic level. DPA is more effective against pentetrazol convulsive seizures where no direct participation of GABAergic receptors seems to occur. The efficiency of potentialisation of GABAergic mediation is a function of the mechanism by which the seizure is triggered.
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PMID:[Effect of sodium dipropylacetate on experimental convulsions produced by pentetrazole and picrotoxin]. 645 30

Sodium Valproate levels in plasma have been measured in 207 children with epilepsy, only 21 of whom were in-patients. No significant correlation could be found between plasma levels and dose of Sodium Valproate expressed as mg/day, mg/kg body weight or mg/m2 surface area. This finding could not be attributed to irregular compliance, concomitant administration of other anticonvulsant drugs, time of sampling after last dose, duration of treatment or age of the child. We could find no evidence of a therapeutic range of plasma levels of Sodium Valproate and the ranges associated with poor (17%), moderate (44%) or good control (39%) of fits were not significantly different. The average daily dose producing an improvement in seizure control was calculated to be 30 mg/kg.
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PMID:Plasma levels of sodium valproate in childhood epilepsy. 681 99

Fever plays an important role in causing disturbances in fluid and electrolyte balance. Hyponatraemia has been thought to enhance the susceptibility to seizures associated with febrile illnesses in childhood. We have studied serum electrolyte levels in children with simple and complicated febrile convulsions. Sodium levels were lower in those children with complicated convulsions in comparison with those having simple convulsions (136.07 +/- 3.06 mmoll-1, mean +/- SD, n = 42, and 137.62 +/- 2.63 mmoll-1, n = 71, respectively; p < 0.01, Student's t-test). The sodium concentrations were lowest in children with repeated seizures (134.20 +/- 2.30 mmoll-1, n = 15) compared with children having simple (p < 0.01, ANOVA, Duncan's test) or other complicated types of febrile convulsions: focal seizures (137.08 +/- 3.82 mmoll-1, n = 12, p < 0.01), seizures lasting longer than 15 minutes (138.00 +/- 2.45 mmoll-1, n = 5, p < 0.05) and children over 5 years (136.70 +/- 2.06 mmoll-1, n = 10, p < 0.05). Serum potassium levels showed no statistically significant differences between the patient groups. Our results show that hyponatraemia may increase the risk for multiple convulsions during the same febrile illness.
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PMID:Low sodium levels in serum are associated with subsequent febrile seizures. 864 53

Sodium valproic acid (VPA) occasionally delays pubertal maturation in children and gonadal and skeletal growth in juvenile, seizure-prone, inbred DBA/2J mice. Fourteen-day-old mice received either VPA or control solution, and the medial preoptic area (mPOA) of the hypothalamus was studied after 4, 7, 10, 14, or 18 days by immunocytochemically processing for gonadotropin-releasing hormone (GnRH). Significant differences were found for the proportion of bipolar to unipolar neurons in the mPOA. VPA may slow pubertal maturation by altering neurochemical systems that normally play an important role in timing maturation of the GnRH pulse generator.
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PMID:A potential mechanism of slowed pubertal maturation after chronic administration of sodium valproic acid. 956 73

3-Benzyl-3-ethyl-2-piperidinone (3-BEP) belongs to a family of compounds that includes alpha- substituted gamma-butyrolactones, gamma-thiobutyrolactones, 2-pyrrolidinones and hexahydro-2H-azepin-2-ones. Many of these drugs exhibit potent in vivo anticonvulsant activity in mice. Previous electrophysiological studies demonstrated that they potentiate gamma-aminobutyric acid- (GABA) mediated chloride currents. This GABAA receptor modulation was thought to be the main mechanism of anticonvulsant activity. We report that 3-BEP also modulates sodium channels. It decreased sodium currents in cultured rat hippocampal neurons in a voltage- and concentration-dependent manner. The drug's apparent affinity increased as neurons were depolarized. At a holding potential of -60 mV, the apparent IC50 was 487 microM. This concentration is comparable to its EC50 for GABAA modulation (575 microM). Current blockade occurred over all activation voltages tested. The steady state inactivation curve was shifted by 600 microM 3-BEP from V50 = -65.3 mV to -72.0 mV, and recovery from inactivation was slowed from tau = 4.9 to 12.8 msec. Sodium current inhibition was not observed for three related compounds, suggesting a degree of chemical specificity for this activity. We conclude that in addition to its known effects on GABAA receptors, 3-BEP modulates sodium channels. Therefore this compound may prevent seizures by both enhancing inhibition and diminishing neuronal excitability.
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PMID:Inhibition of voltage-dependent sodium channels by the anticonvulsant gamma-aminobutyric acid type A receptor modulator, 3-benzyl-3-ethyl-2-piperidinone. 961 37

Convulsive seizures caused by many different stimuli have been shown to induce activator protein-1 (AP-1) transcription factors in the brain, particularly in the hippocampus. Previous results from our laboratory demonstrated that thalamic and cerebral cortical AP-1 DNA- and cyclic AMP responsive element (CRE)- binding activities in the absence seizure model mice were significantly higher than those in nonepileptic control mice. In order to characterize further a correlation between convulsive seizures and inducible transcription factors, we investigated convulsive seizure-dependent increases in AP-1 DNA- and CRE-binding activities in various brain regions of the mice. Administration of pentylentetrazole and kainic acid provoked clonic and limbic type seizures, respectively, and increased AP-1 DNA- and CRE- binding activities in the cerebral cortex and hippocampus but not in other regions. Maximal electric shock (MES) induced tonic convulsions and increased hippocampal and cerebral cortical AP-1 DNA- and CRE- binding activities. Sodium phenobarbital (50 mg/kg, i.p.), an anticonvulsant, suppressed both convulsions and increases in these DNA-binding activities induced by MES. In contrast, ethosuximide, an antiabsence drug, did not affect MES-induced convulsions or increases in these DNA-binding activities. These data suggest that convulsive seizures increase not only AP-1 DNA-binding but also CRE-binding activities in the cerebral cortex and hippocampus. These data combined with our previous results also suggest that regional differences in increases in CRE- and AP-1 DNA-binding activities between convulsive seizures and absence seizures are attributable to differences in the regions and pathways which are responsible for the genesis and spreading seizure activities in the central nervous system.
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PMID:[Cyclic AMP responsive element- and activator protein 1 DNA-binding activities in epilepsy model mice]. 1043 3

Sodium channel blocking, anticonvulsant activity, and sigma (sigma) binding of selected leads in a series of alpha-amino amide anticonvulsants were examined. While anticonvulsant compounds were always endowed with low micromolar sodium (Na+) channel site-2 binding, compounds with low site-2 Na+ channel affinity failed to control seizures. No correlation could be drawn with sigma1 binding. Both anticonvulsant and Na+ channel blocking activities were independent of stereochemistry, while sigma1 binding seems to be favoured by an S-configuration on the aminoamide moiety.
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PMID:Sodium channel activity and sigma binding of 2-aminopropanamide anticonvulsants. 1049

After a short historical review of the development of the pharmaceutical treatment of the epilepsies the author reviews some of the possible strategies to manage patients with the different types of epilepsies and epileptic syndromes using the classical drugs. A strategy used by most of the physicians uses Sodium Valproate as the first line drug for almost all patients. This may be replaced by other drugs according to their efficacy against the different types of seizures to be treated whenever VPA has not enough efficacy or isn t well tolerated. On the other hand epileptologists use the different drugs according to the different epilepsies and epileptic syndromes depending on the relative efficacy of each drug available and the possible side effects. He then describes succinctly the better-known new drugs and makes some comments on the coming drugs now in development. Finally he proceeds to include them in the strategies above described. Lamotrigine and possibly Topiramate are good candidates to replace VPA in the one drug strategy. Lamotrigine, Oxcarbamazepine and possibly Gabapentin may be used in the future as 1st line drugs in selected patients. Vigabatrin is already used as one of the better alternatives for West syndrome and Oxcarbamazepine has replaced Carbamazepine in countries where it s available to the public. Some drawbacks have been apparent with these drugs like the hepatic and haematological toxic effect of Felbamate or the apparently irreversible fields constriction provoked by Vigabatrin, which did limit their use.
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PMID:The new drugs and the strategies to manage epilepsy. 1082 13

Schizencephaly is an extremely rare congenital disease caused by abnormal neuronal migration. The etiology of schizencephaly is not established but vascular disturbance in early childhood could cause this condition. We have cared of a patient with schizencephaly. The patient was 47 year old male. He had focal motor seizure with secondary generalization. Neurological examination revealed, mild left hemiparesis, left pyramidal signs with no sensory impairment, left hemiatrophy, and mirror movement. MRI findings showed schizencephaly, open lip type(type II) in right cerebral hemisphere. His epileptic seizure was controlled by administration of sodium valproate. The possible mechanism of this mirror movement in his left hand and leg could be reorganization of non-affected brain and disinhibition on homolateral pyramidal tract in non-affected left cerebral hemisphere by the transcallosal inhibitory pathyway from affected right cerebral hemisphere. Sodium valpronate can not suppress this mirror movement.
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PMID:[A case with symptomatic epilepsy and mirror movement due to unilateral schizencephaly]. 1093 22

Sodium channels (NaChs) regulate neuronal excitability in both physiological and pathological conditions, including epilepsy and are therefore an important target for antiepileptic drugs. In the present study, we examined the distribution of mRNAs encoding neonatal NaChs II and III alpha-isoforms in control rat hippocampus and after electrically-induced status epilepticus (SE), using nonradioactive in situ hybridization (ISH). Only weak expression of neonatal NaCh II and III mRNAs was observed in control hippocampus. By contrast, increased expression of neonatal NaCh II and III mRNAs was observed 4 h after the induction of SE in neurons of CA1-CA3 and the dentate granule cell layer. These changes were detected only in rats in which SE was successfully induced and persisted, although less intense, for up to 3 months, when rats display spontaneous seizures. Strong expression of neonatal NaCh alpha-isoforms was observed 1 week after SE in microglial cells, as confirmed by double labelling, combining ISH with immunocytochemistry for microglia markers. The increased expression of neonatal isoforms of the NaCh in both neurons and microglial cells may represent a critical mechanism for modulation of neuronal excitability, glial function and pharmacological response to antiepileptic drugs in the course of epileptogenesis.
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PMID:Induction of neonatal sodium channel II and III alpha-isoform mRNAs in neurons and microglia after status epilepticus in the rat hippocampus. 1128 25


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