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)

Neurophysiological interactions between the competitive N-methyl-D-aspartate (NMDA) preferring receptor antagonist, CPP (3-((+-)-2-carboxypiperazine-4-yl)-propyl-1-phosphonate) and the high pressure neurological syndrome (HPNS) have been investigated in the non-human primate Papio anubis. Eight animals were exposed on two occasions to environmental pressures of 81 atmospheres absolute (ATA) in a hyperbaric chamber, using helium and oxygen. One exposure followed pretreatment with CPP (either 5 or 10 mg/kg i.v. plus 5 mg/kg/hr infusion), the other a saline control. Pretreatment with CPP delayed moderate signs of face tremor and myoclonus and abolished severe signs of whole body tremor and seizure activity. By 81 ATA, scores representing severity of HPNS were significantly reduced by CPP to a mean score, reflecting a level of just mild to moderate limb tremoring (P less than 0.001). Changes in the EEG were observed in channels associated with the frontal, parietal and occipital regions of the left cortex. Amplitude and frequency spectra were calculated and changes with pressure in the 4 conventional wavebands were analysed. The most striking change was the complete prevention by CPP of the 100% increase in the amplitude of alpha waves at 81 ATA in the frontal region (P less than 0.001). It is concluded that NMDA transmission has a major role in the expression of HPNS.
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PMID:The effects of the competitive NMDA receptor antagonist CPP on the high pressure neurological syndrome in a primate model. 183 61

Scopolamine (Hyoscine), an anticholinergic compound is widely used for the prophylaxis and treatment of motion sickness and might be used with oxygen diving and hyperbaric oxygen therapy. We therefore decided to test the interaction of scopolamine with oxygen at high pressure. Thirty-six rats implanted with cortical EEG electrodes were injected subcutaneously with two doses of scopolamine (0.02 or 0.2 mg.kg-1), or the vehicle (saline), 30 min before exposure to 5 atm abs (0.5 MPa) oxygen. Electroencephalogram and heart rate were monitored continuously. Spectral analysis of the EEG was carried out, and the duration of the latent period before convulsions was determined. No significant difference was found in the duration of the latent period between the control rats receiving vehicle (saline) and rats injected with scopolamine (n = 12 for each group). Changes in background EEG activity and maximal dilation of the pupil were detected at both scopolamine doses. Heart rate significantly decreased at 0.02 mg.kg-1 and increased at the dose of 0.2 mg.kg-1 scopolamine. Our findings indicate that the duration of the latent period preceding hyperoxic seizures is not altered by scopolamine in rats; however, other side effects of the drug regarding visual and cardiovascular symptoms should be considered when scopolamine is used in combination with hyperbaric oxygen.
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PMID:Hyperbaric oxygen and scopolamine. 185 67

Potent anticonvulsant activity has been reported for (R,S)-2-acetamido-N-benzyl-2-methylacetamide (2a). Select alpha-heteroatom substituted derivatives of 2a have been prepared (26 examples) in which the alpha-methyl group has been replaced by nitrogen (3a-q), oxygen (3r-u), and sulfur (3v-z) containing moieties. The functionalized amino acid derivatives were evaluated in the maximal electroshock seizure (MES) and horizontal screen (tox) tests in mice. The most active compounds were (R,S)-2-acetamido-N-benzyl-2-(methoxyamino)acetamide (31), and (R,S)-2-acetamido-N-benzyl-2-(methoxymethylamino)acetamide (3n). After ip administration, the MES ED50 values for 31 (6.2 mg/kg) and 3n (6.7 mg/kg) compared favorably with phenytoin (9.50 mg/kg).
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PMID:Preparation and anticonvulsant activity of a series of functionalized alpha-heteroatom-substituted amino acids. 187 41

An examination of the cellular and molecular mechanisms of neuronal cell damage may lead to the design of pharmacologic interventions during presumed or actual fetal asphyxia. Hypoxia-ischemia in its severest form results in insufficient adenosine 5'-triphosphate production. The most important effect of this is failure of adenosine 5'-triphosphate-dependent membrane functions, which maintain ionic homeostasis, that is, ionic pumping. There is K+ efflux and Na+ influx across the cell membrane, depolarization of the cell membrane, opening of the voltage-dependent calcium channels, and entrance of Ca++ into the cell. Cytosolic Ca++ is also increased by Ca++ efflux from the mitochondria and the sarcoplasmic reticulum. Ca++ is a toxin in high cytosolic concentrations; it activates phospholipases A and C, which cause membrane breakdown and release of free fatty acids, including arachidonic acid. The membrane is damaged, lysis occurs, and the neuron dies. High cytosolic Ca++ also causes release of excitatory amino acids (especially glutamate), which overwhelm the suppressant neurotransmitters, causing seizures, increased metabolism, and aggravation of the insufficient adenosine 5'-triphosphate availability. Thromboxane A2 is generated from arachidonic acid, increasing smooth muscle tone and thereby worsening the ischemia. Cyclooxygenase activity also results in formation of oxygen-free radicals that contribute to cell membrane damage, lysis, and death. Possibilities for pharmacologic interventions include (1) calcium channel blockers and antagonists, (2) excitatory neurotransmitter blockers, (3) oxygen-free radical scavengers (e.g., superoxide dismutase), (4) cyclooxygenase or prostaglandin synthesis inhibitors, and (5) seizure suppressants (e.g., phenobarbital). Some of these treatments have been shown experimentally to limit neuronal death in the adult and fetus, and after more investigative work they may be applicable to clinical practice.
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PMID:Mechanisms of asphyxial brain damage, and possible pharmacologic interventions, in the fetus. 190 82

When human divers or experimental animals are exposed to high pressure, they develop the High Pressure Neurological Syndrome (HPNS). Male Sprague-Dawley rats were exposed to high pressure in a conventional helium-oxygen breathing mixture to 80 bars. Pressure-induced behavioral motor disturbances including hyperlocomotor activity (HLA), tremor and myoclonia were monitored with a noninvasive piezoelectrical sensor device enabling a without discontinuity long-term analysis. New data were obtained on the development of the HPNS behavioral motor disturbances. Indeed, the present results suggest myoclonia would be more sensitive to constant high pressure exposure, while HLA and tremor would be more sensitive to increasing pressure. Moreover, myoclonia were found to occur significantly later in rats which developed epileptic seizures than in other. The present results constitute the quantitative basis of HPNS motor disturbances for future pharmacological pressure experiments.
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PMID:Quantitative study of behavioral disturbances in rats exposed to high pressure. 191 Mar 48

The effects of acute changes in plasma magnesium concentration on the threshold for lidocaine-induced seizures were evaluated in mechanically ventilated rats receiving 70% nitrous oxide and 30% oxygen. In experiment 1, male rats were intravenously administered either 0.9% sodium chloride (group I) or 5.0% magnesium sulfate to elevate plasma magnesium levels to 5.8 +/- 0.1 (group II) or 10.5 +/- 1.0 mg/dl (group III). In experiment 2, pregnant rats were intravenously administered either 0.9% sodium chloride (normomagnesemia) or magnesium sulfate, resulting in a plasma magnesium concentration of 7.8 +/- 1.4 mg/dl. Thirty minutes later, a continuous intravenous infusion of lidocaine (2.3 mg/kg per minute) was begun in both experiments. Biparietal electroencephalographic activity was monitored continuously. At the onset of electroencephalographic seizure activity, arterial plasma magnesium and lidocaine concentrations were measured. In groups I and III (experiment 1), brain parenchymal magnesium was also assayed. There were no differences in plasma lidocaine concentrations (in experiments 1 or 2) between saline solution and hypermagnesemic groups at onset of seizures. Brain magnesium level was unaltered by magnesium sulfate infusion. We conclude that acute administration of magnesium sulfate alters neither brain magnesium level nor the plasma lidocaine concentration associated with onset of electroencephalographic seizures.
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PMID:Effects of acute hypermagnesemia on the threshold for lidocaine-induced seizures in the rat. 199 23

Propofol was used for 1,350 sessions of electro-convulsive therapy (ECT). After 0.5 mg of intravenous atropine, patients received 1 to 1.5 mg.kg-1 bolus of propofol over a period of 20 seconds or less. This was convenient for loss of the eye-lash reflex. A bolus of 15 to 20 mg suxamethonium was given, in non allergic patients, to prevent trauma from the seizure. The patient was hyperventilated with pure oxygen through a facial mask. The electric shock was delivered bitemporally after a dental protection had been inserted. For each patient, the following data were noted: sex, use of tricyclic antidepressant drugs, atopy, amount of administered propofol and the effective intensity of the electric shock. The 99 patients were given 16.27 +/- 14 ECT sessions. Among them 26 took antidepressant drugs and 34 were atopic. There was no difference, except for weight, between the 25 men and 74 women. The mean dose of propofol was 1.37 +/- 0.3 mg.kg-1. The dose decreased with increasing age. There was no statistical relationship between the amount of propofol and intensity of the electric shock required to set off a seizure. The use of antidepressant drugs, and atopy did not influence the required amount of propofol. Speed of injection seemed to be the determining factor for narcosis with low doses of propofol. Hyperoxia and hypocapnia induced by hyperventilating with pure oxygen seemed to facilitate occurrence and duration of seizures. Although propofol has been said to reduce the length of seizures, there is controversy concerning the ECT efficacy criteria.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Use of propofol in 1350 anesthetized patients for electroconvulsive therapy]. 200 69

Leukotrienes and prostaglandins are formed from arachidonic acid by activation of local phospholipases in pathological conditions such as cerebral ischemia, subarachnoid hemorrhage, cerebral tumors and seizures. These mediators, especially leukotrienes have a very potent vasoconstrictor effect on cerebral arteries. Experimental studies have shown that this effect, by increasing vascular permeability causes vasogenic edema that contributes to the ischemic penumbra. In this study, after developing an experimental animal model simulating the concept of ischemic penumbra in the rat, the levels of leukotriene C and prostaglandin E2 produced in the forebrain were measured and the effects of these mediators in prolonged ischemia were investigated. The results, in the first 4 min of ischemia, showed that the arachidonic acid metabolites, particularly, leukotriene C4, reached a peak in the ischemic cerebral tissue in association with leukocyte accumulation. Later in the 15th min, significant decreases in leukotriene C4 and prostaglandin E2 levels were seen. In the 1st and 4th h, probably due to the stimulation of the relevant enzymes by free oxygen radicals in the ischemic tissue; the levels increase again, returning to control values by the 12th h. It is concluded that the use of lipoxygenase inhibitors and free radical scavengers may be helpful to limit the infarct area in the first 4 h of ischemia.
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PMID:The alterations of leukotriene C4 and prostaglandin E2 levels following different ischemic periods in rat brain tissue. 201 13

The main manifestations of CNS oxygen toxicity are generalized tonic-clonic seizures. We tested the protective effect of 2 antiepileptic drugs, carbamazepine and ethosuximide, which are commonly used for the treatment of generalized seizures, on hyperbaric oxygen-induced convulsions. Rats implanted with chronic cortical electrodes for continuous EEG monitoring were injected i.p. with either carbamazepine (5 doses in the range of 1.5-50 mg/kg), ethosuximide (400 mg/kg), or their vehicles (40% propylene glycol and saline, respectively). The rats were exposed to 5 ATA (0.5 MPa) oxygen. The duration of the latency until the appearance of electrical discharges in the EEG was used as an index of toxicity. Ethosuximide did not protect against hyperoxic seizures. In contrast, rats pretreated (30 min) with carbamazepine exhibited a dose-related protective effect against hyperoxically induced seizures. The results of our study suggest that carbamazepine should be considered for prevention of oxygen-induced seizures during hyperbaric oxygen therapy.
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PMID:The effect of carbamazepine and ethosuximide on hyperoxic seizures. 206 42

Hyperglycemic, but not normoglycemic cats exposed to anoxia develop neurologic signs following reoxygenation including fasciculations, focal and tonic-clonic seizures and coma after a symptom-free period. These symptomatic hyperglycemic cats may develop brain edema and will show diffuse neuronal injury or brain infarction depending on length of survival. Brain mitochondria isolated from symptomatic but not asymptomatic cats have decreased ADP- and uncoupler-stimulated oxygen consumption rates. Since impaired respiration could result from altered electron transport chain function, we measured cytochrome c, b, and aa3 concentrations and the activities of the five electron transfer complexes in isolated brain mitochondria. In symptomatic cats marked alterations were present in particular in complex IV, cytochrome oxidase, with a 57% reduction in activity and a 45% reduction in prosthetic group (cytochrome aa3) concentrations. Less marked reductions in other segments of the chain included 27% and 41% decreases, respectively, in cytochrome c concentrations and in electron transfer complex II, succinate:ubiquinone oxidoreductase activity. Cytochrome b concentrations and complex I, II and V activities were unchanged. Small but significant decreases in cytochrome aa3 concentrations (18%) and cytochrome oxidase activity (20%) were also present in mitochondria from postanoxic hyperglycemic cats prior to appearance of neurologic signs. These results indicate that delayed decreases in the activities of specific electron transfer complexes are correlated with impaired mitochondrial respiration and neurologic deterioration in postanoxic hyperglycemic cats. However, it is presently unclear if these postanoxic brain mitochondrial alterations are primary or secondary events in the development of brain injury.
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PMID:Delayed decreases in specific brain mitochondrial electron transfer complex activities and cytochrome concentrations following anoxia/ischemia. 208 31


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