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)

When mice were kept continuously intoxicated by inhalation of ethanol, physical dependence developed progressively, reaching its maximum in about 2 weeks. Decay of physical dependence during periods of sobriety was complete in about a day. These rapid time courses are consistent with a theoretical model in which alcohol inhibits and simultaneously stabilizes its target. This target may be located in central adrenergic synapses, because interference with function of such synapses facilitated the alcohol withdrawal reaction and because strain differences in withdrawal seizure scores correlated well with strain differences in reserpine effects.
 ...
PMID:Drug dependence as an adaptive response: studies with ethanol in mice. 117 82

Genetically seizure susceptible DBA/1/Bg mice fed 10% ethanol in their drinking water exhibited a marked diurnal variation in blood alcohol levels. At peak levels, sound-induced seizures were significantly reduced. At trough levels, seizures remained unaffected. Ethanol administered during early development enhanced seizures at post-weaning age. Such alcohol-augmented seizures were suppressed by ethanol feeding during the testing period, to the same base level as in animals not pretreated with ethanol in early life.
 ...
PMID:Suppressant effects of alcohol on audiogenic seizures. 123 99

Rats received intragastric intubations of ethanol at 8 hr intervals for 1, 7, 15 or 30 days. The dosage for each animal was one which produced observable signs of intoxication 1 hr after the intubation. All of the rats in the experimental groups developed a tolerance to ethanol as indicated by the increasing dose required to induce intoxication, but the degree of tolerance was related to the duration of the ethanol administration. During the withdrawal period the incidence of hyperreactivity, convulsive symptoms, and the susceptibility to audiogenic seizures was determined for all 4 groups. Although every experimental animal displayed withdrawal symptoms, the incidence of these symptoms was found to be an increasing, negatively accelerated function of the duration of ethanol exposure. For situations where voluntary consumption of alcohol is not necessary this method is a simple, controlled, reliable, way of inducing ethanol tolerance and physical dependence in rats.
 ...
PMID:Simple method for producing an alcohol withdrawal syndrome in rats. 123 71

Tryptophan hydroxylase (TPH) activity was determined in whole brain from male C57BL/10/Bg and DBA/1Bg mice at 14 different ages between postnatal days 4 and 33. Brain TPH activity was higher at every age in C57BL/10/Bg than in DBA/1/Bg mice, the difference being 30-50% after day 20. The apparent Km of the enzyme for substrate was identical (1.4 X 10(-5) M) in both strains. The reciprocal F1's between DBA/1/Bg and C57BL/10/Bg strains were similar in TPH activity, being slighlty lower than the predicted midparental value. At 30 days of age, C57BL/6/Bg males also had high TPH activity, indistinguishable from the C57BL/10/Bg strain. Audiogenic seizure susceptibility in these strains and their hybrid F1's was inversely correlated with their brain TPH activities. These results indicate that seizure susceptibility and aggression in mice may be related to the serotonergic activity in the brain. In the case of seizures, ethanol-induced susceptibility to audiogenic seizures in mice was enhanced by reserpine, and the effect of reserpine could be reversed by 5-HTP but not by DOPA. Furthermore, p-chlorophenylalanine also enhanced such susceptibility, whereas alpha-methyltyrosine had no effect. In the withdrawal audiogenic seizures in mice during chronic ethanol treatment, adrenalectomy blocked the ethanol-induced increase of brain TPH activity and also prevented the withdrawal seizures. Our results are consistent with the hypothesis that the serotonergic system is among the components regulating excitability in the brain.
 ...
PMID:Pharmacogenetic studies of the serotonergic system in association with convulsive seizures in mice. 124 14

One of ethanol's actions after acute exposure is anticonvulsant activity whereas withdrawal from chronic ethanol exposure increases convulsant activity. An increase in neuronal transmission in the GABAergic pathways from striatum to the substantia nigra (SN) and a decrease in GABAergic transmission from SN to superior colliculus (SC) both appear to play a major role in inhibiting seizure propagation. If this is the case, then the changes in seizure sensitivity caused by ethanol may be expected to affect GABAergic transmission in opposite ways in SN and SC. We measured the effects of in vitro ethanol on pre- and postsynaptic indices of GABA transmission using SN and SC tissue from both ethanol-naive rats and rats given ethanol in their drinking water for 24 days and then withdrawn for 24 hr, a treatment that decreases seizure latency. While ethanol inhibited 3H-GABA release from slices of SC at low concentrations (20-100 nM), much higher concentrations were required to inhibit release from SN (100-500 mM). In fact, release from SN was increased by low concentrations of ethanol. Ethanol in vitro (20-1000 mM) also inhibited specific binding of 35S-TBPS to the GABAA receptor but this effect was similar in both potency and efficacy in SC and SN. Next, the in vitro effects of ethanol were measured in rats that had consumed an average of 9.8 g ethanol/kg body weight/day and were then withdrawn for 24 hr. Ethanol inhibition of 3H-GABA release from SC was significantly less in ethanol-treated rats compared to controls whereas the inhibitory effect of ethanol was increased in SN from ethanol-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Alcohol Clin Exp Res 1992 Apr
PMID:Selective changes in GABAergic transmission in substantia nigra and superior colliculus caused by ethanol and ethanol withdrawal. 131 35

A hypothesis is presented to explain the influence of alcohol on glutamate generated excitotoxicity. Chronic alcohol exposure is reported to increase glutamate-N-methyl-D-aspartate (NMDA) receptors and calcium ion channel activity, resulting in the neurotoxicity and seizure activity associated with alcohol withdrawal in certain persons. Recent information indicates that nitric oxide is responsible for the neurotoxicity associated with excessive glutamate stimulation of NMDA receptors. Thus, it is hypothesized that nitric oxide is involved in producing the neurotoxicity and cell disturbances associated with chronic alcohol exposure.
Alcohol Clin Exp Res 1992 Jun
PMID:Alcohol, nitric oxide, and neurotoxicity: is there a connection?--a review. 132 Aug 8

There is a growing body of evidence suggesting that corticosteroids contribute to the increased neural excitability observed during ethanol withdrawal. In the present study, this was further investigated using mouse strains which differ in ethanol withdrawal severity. DBA/2 (DBA) mice were found to display more severe acute ethanol withdrawal seizures than C57BL/6 (C57) mice. Additionally, DBA mice showed a greater stress response than C57 mice, as measured by higher plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone, to an acute dose of ethanol. Mimicking withdrawal plasma corticosterone levels by administering corticosterone to ethanol-naive mice resulted in increases in handling-induced convulsions in the range observed during withdrawal. There did not appear to be a strain difference in sensitivity to the excitatory effects of corticosterone. In summary, the greater stress response to ethanol by DBA mice may account, in part, for the more severe ethanol withdrawal syndrome of this strain.
 ...
PMID:Genetic differences in hypothalamic-pituitary-adrenal axis responsiveness to acute ethanol and acute ethanol withdrawal. 132 Sep 85

Female rats have a higher threshold than males for seizures induced by the convulsant pentylenetetrazol, a GABAA receptor-chloride channel complex blocker. No sex difference was observed for the anticonvulsant activities of ethanol or diazepam to protect against pentylenetetrazol seizures. Ovariectomy reduces the pentylenetetrazol seizure threshold of females to that of males. In contrast, females have a lower threshold than males to electroshock seizures. Pentylenetetrazol receptors were compared in males and females and gonadectomized animals by binding of several radioligands to the GABAA receptor complex. No differences were found for these four groups of animals in the binding of [3H]flunitrazepam to the benzodiazepine sites and [35S]t-butyl bicyclophosphorothionate ([35S]TBPS) to the chloride channel/convulsant sites in membrane homogenates, nor for allosteric modulation of binding by GABA, the steroid anesthetic alphaxalone, or the benzodiazepine Ro 5-4864. In tissue section autoradiography, no difference was observed for these same assays nor for the binding of [3H]muscimol in the presence and absence of alphaxalone in several major regions. We conclude that circulating female sex hormones, possibly neurosteroid metabolites of progesterone, known to interact directly with the GABAA receptor complex, are involved in the sex differences in pentylenetetrazol seizure susceptibility.
 ...
PMID:Sex differences in sensitivity to pentylenetetrazol but not in GABAA receptor binding. 133 80

The benzodiazepine antagonist flumazenil is a very valuable tool in the diagnosis and treatment of intoxications in which benzodiazepines are involved. In case of a positive response, patients will regain consciousness immediately, thus verifying the diagnosis and making a brief history possible to identify other drugs that might be involved. Moreover, invasive diagnostic and therapeutic procedures like gastric lavage, lumbar puncture, mechanical ventilation, etc., may then be unnecessary. In cases of pure benzodiazepine overdose a single injection of flumazenil 0.2mg should be given, followed by individually titrated increments of 0.1 mg/min until the patient is awake and responsive. In these cases a total dose of 2mg is usually sufficient. Higher doses of flumazenil may be necessary in cases of combined drug overdose. Because of its high therapeutic index, the administration of flumazenil is usually not accompanied by serious adverse effects. Benzodiazepine withdrawal syndromes characterised by transient anxiety and depression can occur, but the incidence is low. Increases of blood pressure and heart rate due to a release of catecholamines are possible, which might endanger patients with cardiovascular diseases. In severe cases, seizures have been observed which usually respond well to small doses of benzodiazepine agonists. In all cases of successful treatment it should be remembered that the effect of flumazenil deteriorates after 1 to 2h, which usually leads at first to resedation. In these patients additional bolus injections or a continuous infusion (0.1 to 0.5 mg/h) may be necessary. The effectiveness of flumazenil in cases of alcohol (ethanol) poisoning is questionable and should be further investigated.
 ...
PMID:Benzodiazepine antagonists. An update of their role in the emergency care of overdose patients. 135 15

Abecarnil, a beta-carboline acting at benzodiazepine receptors, has been shown to have anxiolytic and anticonvulsant properties in a number of models. It has reduced muscle relaxant and incoordinating effects in comparison to diazepam. Given the wide clinical application of diazepam to prevent alcohol withdrawal seizures, a genetic animal model was employed to compare abecarnil with diazepam for its anti-withdrawal effects. Withdrawal Seizure Prone (WSP) mice, genetically selected to develop severe handling-induced convulsions after withdrawal from chronic ethanol treatment, were exposed to ethanol vapor for 24 h. WSP mice given doses of abecarnil or diazepam at the peak of withdrawal had significantly reduced handling-induced convulsion scores. While abecarnil was slightly more potent than diazepam, its effects were shorter-lasting. Similar results were seen in an experiment where withdrawal handling-induced convulsions were assessed after a single high-dose ethanol injection. Abecarnil and diazepam also reduced the smaller handling-induced convulsion scores seen in naive WSP mice. Single doses of abecarnil or diazepam did not lead to a rebound elevation of handling-induced convulsion scores suggestive of a withdrawal reaction.
 ...
PMID:Antagonism of ethanol withdrawal convulsions in Withdrawal Seizure Prone mice by diazepam and abecarnil. 136 Sep 3


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