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)

C57BL/6J male mice rendered physically dependent on phenobarbital exhibited significantly lower whole-brain and serum-magnesium concentrations than did control mice. The symptoms of phenobarbital withdrawal were remarkably similar to those seen in magnesium-deficient mice exposed to a low-magnesium diet without drug exposure. These findings suggest that brain magnesium deficits produced by chronic phenobarbital withdrawal could contribute to the observed phenobarbital withdrawal syndrome. Administration of MgSO4 during withdrawal significantly reduced the incidence of tonicclonic and lethal tonic seizures.
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PMID:Barbiturate withdrawal and magnesium deficiency in mice. 10 34

The use of magnesium sulfate (MgSO4) as an anticonvulsant is controversial. Status epilepticus was induced in 0.5% halothane-anesthetized Wistar rats with a threshold (90 mg/kg) or suprathreshold (200 mg/kg) dose of intravenous (i.v.) pentylenetetrazol (PTZ) under stereotactic hippocampal depth electrode monitoring. Fifteen minutes after seizure induction, the maximum hemodynamically tolerated dose of MgSO4 (10 mg/kg/min in 22 min) was administered i.v. MgSO4 was ineffective in altering seizure discharge. A subgroup of nine animals received hypertonic mannitol before MgSO4 to open the blood-brain barrier (BBB) to facilitate Mg2+ CNS penetration. Again MgSO4 was ineffective in attenuating epileptic activity. These results support the contention that MgSO4 is not an effective treatment for status epilepticus. We hypothesize that because Mg2+ blocks Ca2+ influx into the neuron through the N-methyl-D-aspartate (NMDA) receptor-operated calcium channel in a voltage-dependent manner it would be ineffective in neurons that are continuously depolarizing as in status epilepticus.
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PMID:Effects of magnesium sulfate on pentylenetetrazol-induced status epilepticus. 183 Nov 20

The effect of acutely elevated serum magnesium on the CNS and cardiac toxicity of bupivacaine was studied. Anesthesia was induced in mongrel dogs with thiopental, 25 mg/kg, and ventilation was controlled. Sedation was maintained with fentanyl (25 micrograms/kg bolus and 5 micrograms.kg-1h-1) and pancuronium (0.15 mg/kg bolus and 0.05 mg.kg-1h-1) provided paralysis. Two hours after the thiopental bolus, all animals received an intravenous (iv) infusion of bupivacaine (1 mg.kg-1 min-1). The control group (5 animals) received bupivacaine only. The Mg++ group (5 animals) received MgSO4 140 mg/kg iv and 80 mg.kg-1 h-1 15 min prior to beginning the bupivacaine infusion. Lead II ECG, cardiac hemodynamics, and two-channel EEG were continuously monitored. Serum magnesium concentrations in the Mg++ group rose from 0.67 mM (1.3 mEq/L) to 2.42 mM (4.8 mEq/L). The bupivacaine infusion caused PR and QRS interval prolongation in both groups, but QRS widening was greater in the control group. QT interval corrected for heart rate (QTIc) lengthened only in the control group. A depression of left ventricular stroke work index (LVSWI) occurred to an equal extent in both groups. The seizure dose of bupivacaine was not different between the two groups: 12.9 +/- 2.3 (SEM) mg/kg in the control group and 13.9 +/- 2.5 mg/kg in the Mg++ group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of magnesium sulfate administration on cerebral and cardiac toxicity of bupivacaine in dogs. 230 66

We studied the effects of parenteral magnesium sulfate (MgSO4) administration on electroencephalographic seizures induced by hyperbaric oxygen (HBO) in awake rats. Sixteen rats chronically implanted with electrocorticographic electrodes were preinjected i.p. with either vehicle or 3 mmol/kg MgSO4 (the latter resulted in serum levels of 3.5-5.5 mmol/liter) and then exposed to 6 ATA O2 in a pressure chamber. The time to develop an electric ichtal seizure was measured and compared to that in the same animal receiving the alternate treatment 3 days later. Mean and median times after the magnesium treatment were almost double those of vehicle administration. A central anticonvulsive action of magnesium, which should be investigated over the entire HBO range, is indicated.
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PMID:Magnesium sulfate suppresses electroencephalographic manifestations of CNS oxygen toxicity. 231 59

Magnesium sulfate has been used as an anticonvulsant in the treatment of eclampsia, but efficacy of magnesium in other types of seizure disorders is poorly documented. We examined the effects of magnesium sulfate (MgSO4) on seizures produced in mice by maximal electroshock (MES) and pentylenetetrazol (PTZ), MgSO4 injection (6.7 mEq/kg i.p.) caused weakness in all animals. With suprathreshold electroshock, 10/10 controls and 11/12 treated animals had seizures with tonic hind limb extension (P = NS). Electroshock threshold was unaltered by magnesium treatment (n = 48; P = 0.47). PTZ induced clonic seizures in 12/12 controls and 5/14 treated animals (P less than 0.05). This difference was likely due to muscular weakness because frequency of EEG spikes was the same in PTZ and PTZ + MgSO4 groups. Mean serum magnesium levels were 2.3 +/- 0.3 mEq/l in animals not given MgSO4; 10.9 +/- 1.4 mEq/l and 12.8 +/- 2.2 mEq/l in treated animals with and without seizures (P = NS). We conclude that magnesium sulfate had no significant anticonvulsant activity in mouse MES and PTZ models for epilepsy. The relevance of these findings to the possible efficacy of magnesium sulfate in eclamptic seizures and other types of epilepsy remains to be determined.
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PMID:Parenteral magnesium sulfate fails to control electroshock and pentylenetetrazol seizures in mice. 261 92

Several excitatory amino acid antagonists were tested for an ability to prevent spontaneous convulsions seen during the barbital abstinence syndrome in rats. Barbital-dependent animals were continuously infused intracerebroventricularly (i.c.v.) for the first 48 h following barbital withdrawal with either saline, 2-amino-7-phosphonoheptanoic acid (APH), magnesium sulfate, glutamyldiethyl ester (GDEE) or cis-2,3-piperidine dicarboxylic acid (PDA) using the highest dosages which did not affect normal behavior of the rats. All animals were observed continuously from 12 to 48 h postwithdrawal and the number of spontaneous convulsions observed in each animal was recorded. After this time, animals were killed by focused microwave irradiation and the cerebellas were collected for determination of cyclic guanosine monophosphate (cGMP) levels. While both APH and MgSO4 dramatically prevented convulsions, only APH prevented the withdrawal-induced elevation of cerebellar cGMP. PDA and GDEE had no statistically significant effect on either cerebellar cGMP levels or on convulsive activity. Although the effect of GDEE was not statistically significant, the number of convulsions was reduced to 1/3 those seen in control animals. These data implicate N-methyl-d-aspartate (NMDA) receptor-mediated pathways in seizure activity associated with the barbital abstinence syndrome and show that the withdrawal-induced elevation of cerebellar cGMP can occur without the induction of convulsions.
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PMID:Anticonvulsive activity of several excitatory amino acid antagonists against barbital withdrawal-induced spontaneous convulsions. 337 64

Electroencephalograms (EEGs) were recorded in 36 eclamptic, 14 preeclamptic, and 13 normotensive control patients. In the eclamptic group, EEGs were recorded while patients were receiving intravenous magnesium sulfate (MgSO4) with serum magnesium (Mg) levels of 4.5 to 11 mg/dL, and recorded again after MgSO4 was discontinued (serum Mg levels 1.8 to 2.5 mg/dL). In preeclamptic patients, EEGs were recorded before starting MgSO4, during administration of the loading dose (serum Mg levels 6 to 10 mg/dL), and eight hours through the maintenance dose (serum Mg levels 3.6 to 6.2 mg/dL). Twenty-seven (75%) eclamptic patients had abnormal EEGs, four patients showed paroxysmal spike activity, and the others showed focal or diffuse slowing (delta waves). Seven (50%) preeclamptic women had abnormal EEGs (all had generalized slowing). In preeclamptic-eclamptic patients who had serial EEG recordings, the gross EEG findings obtained during MgSO4 infusion and in the absence of MgSO4 were similar. In addition, the abnormal EEG findings were frequent despite the serum Mg levels considered therapeutic in the clinical management of these patients. Two eclamptic patients had seizure activity at serum Mg levels of 9.6 and 11 mg/dL. These findings suggested that abnormal EEGs are frequent in preeclamptic-eclamptic patients. Abnormal EEG findings in such patients are not altered by serum Mg levels achieved in the clinical management of these patients.
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PMID:Effect of magnesium sulfate on electroencephalographic findings in preeclampsia-eclampsia. 673 59

The occurrence of seizures in preeclamptic and eclamptic women is considered very unlikely during treatment with the standard dose of continuous intravenous magnesium sulfate. During a 21-month period, the authors encountered 13 patients who developed seizure activity while receiving intravenous MgSO4. Serum magnesium (Mg) levels at the time of seizure were below the therapeutic range in 11 of the 13 patients, thus prompting a study of serum Mg levels in preeclamptic patients treated with MgSO4. Random serum Mg samples were obtained from 120 patients treated with intravenous MgSO4 for preeclampsia-eclampsia. The samples were collected 2 to 48 hours after the loading dose and while the patients were taking a maintenance dose of either 1, 2, or 3 g/hr. When a maintenance dose of 1 or 2 g/hr was used, 98 and 50% of the respective serum magnesium values were below levels considered therapeutic by several authors. Therapeutic levels were achieved in ll patients receiving a maintenance dose of 3 g/hr. The recommended maintenance dose of MgSO4 of 1 g/hr was found insufficient to prevent the occurrence of eclamptic seizures in some preeclamptic patients.
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PMID:Reassessment of intravenous MgSO4 therapy in preeclampsia-eclampsia. 746 24

1. Magnesium sulphate (MgSO4) has been used for many years in the prevention of eclamptic seizures, but its mechanism of action has never been elucidated. Recent studies suggest that cerebral vasospasm is an important feature of eclampsia and we have developed and tested the hypothesis that MgSO4 can reverse cerebral vasoconstriction. 2. Studies were performed in conscious, male Long Evans rats with pulsed Doppler probes sutured around both common carotid arteries after the external carotid artery had been ligated on the left, thus allowing simultaneous measurement of changes in common and internal carotid blood flow. Intravascular catheters were placed in the abdominal aorta for measurement of systemic blood pressure and in the right jugular vein for administration of drugs. Mean arterial blood pressure and mean Doppler shift signals were used to calculate percentage changes in common and internal carotid vascular conductance. 3. After a period of recovery the animals were infused with endothelin-1, angiotensin II, neuropeptide-Y or NG-nitro-L-arginine methyl ester alone or in combination, and MgSO4 in low or high dose was infused when the effects of the vasoconstrictors had become established. 4. MgSO4 itself, at the low dose, had no effect on carotid vascular conductance. Endothelin-1, angiotensin II and neuropeptide-Y all reduced common and internal carotid vascular conductance and this effect was significantly attenuated by low dose MgSO4. The carotid vasoconstrictor action of endothelin-1 was completely abolished by high dose MgSO4.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Magnesium sulphate reverses the carotid vasoconstriction caused by endothelin-I, angiotensin II and neuropeptide-Y, but not that caused by NG-nitro-L-arginine methyl ester, in conscious rats. 840 87

Lidocaine and MgSO4 are often coadministered to patients with pregnancy-induced hypertension. This study examined whether MgSO4 alters the lidocaine-seizure threshold in the rat and, if so, whether systemic MgSO4 administration is as effective as intracerebroventricular MgSO4 infusion. In Experiment 1, rats were administered 50% MgSO4 or 0.9% NaCl intravenously (IV) (20 microL/h) for 5 days. In Experiment 2, rats were administered 0.9% NaCl, 0.8% MgSO4, or 2.0% MgSO4 (10 microL/h) via intracerebroventricular infusion for 24 h. All rats then underwent continuous IV lidocaine infusion until onset of electroencephalographic seizures. In Experiment 1, plasma [Mg2+] was greater in the MgSO4 group (5.1 +/- 1.5 mg/dL vs 1.8 +/- 0.3 mg/dL) but neither the dose of lidocaine required to induce seizures (MgSO4 = 19 +/- 2 mg/kg; saline = 23 +/- 5 mg/kg) nor brain [Mg2+] (MgSO4 = 794 +/- 17 micrograms/g; saline = 788 +/- 33 micrograms/g) were changed. In Experiment 2, intracerebroventricular MgSO4 increased both brain [Mg2+] (2% MgSO4 = 923 +/- 79 micrograms/g; saline = 788 +/- 35 micrograms/g) and the lidocaine seizure dose (2% MgSO4 = 39 +/- 7 mg/kg; saline = 26 +/- 3 mg/kg). Although intracerebroventricular administration of MgSO4 produces an anticonvulsant effect, chronic hypermagnesemia does not alter whole brain [Mg2+] and therefore offers no protection from lidocaine-induced seizures in this model.
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PMID:The effects of plasma and brain magnesium concentrations on lidocaine-induced seizures in the rat. 894 90


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