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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exposure to monomethylhydrazine (MMH), a common rocket propellant, can cause dose-related central nervous system (CNS) disturbances ranging from tremors to tonic-clonic convulsions to death. MMH inhibits gamma-aminobutyric acid (GABA) synthesis in the CNS. Diazepam (BZ) acts at the GABA receptor site, and it is also here that ivermectin (AVM) is pharmacologically active. Mice were injected with 30 mg/kg MMH. Groups of 12 mice each were then given varying doses of AVM (5, 10 and 15 mg/kg), or AVM + BZ combinations (5 mg/kg AVM with 5 mg/kg BZ, 10 mg/kg AVM with 5 mg/kg BZ). Time to first convulsion and time to death were recorded over the next 7 h and all groups were monitored over the next 7 days. Times to convulsion were not altered with AVM alone, but death was significantly prevented with AVM dosages. A treatment of 10 mg/kg AVM with 5 mg/kg BZ resulted in no seizures or deaths.
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PMID:Modulation of monomethylhydrazine-induced seizures by ivermectin. 185 61

Sodium azide is a chemical of rapidly growing commercial importance with a high acute toxicity and an unknown mechanism of action. Although it has some chemical properties and biological effects in common with cyanide, its lethality does not appear to be due to inhibition of cytochrome oxidase. Unlike cyanide it is a potent vasodilator and inhibitor of platelet aggregation presumably by virtue of its conversion to nitric oxide in vivo and in isolated preparations of blood vessels and thrombocytes. It is not clear whether the high toxicity of azide is due to nitric oxide or to the parent anion. Of a number of possible azide antagonists tested in intact mice only phenobarbital in both anesthetic and subanesthetic doses afforded statistically significant protection against death. Diazepam, phenytoin, and an anesthetic dose of a ketamine/xylazine combination had no effect. Major motor seizures are sometimes seen in human azide poisoning, and these are a regular feature of azide poisoning in laboratory rodents. Solutions of nitric oxide given systemically to mice produced no signs of toxicity, but doses 1,000-fold lower placed in the cerebroventricular system of rats produced brief but violent tonic convulsive episodes. A dose of 0.61 mmol/kg azide as given systemically regularly produced convulsions whereas a dose of 6 mumol/kg given icv produced seizures in rats. The icv convulsive dose of azide was 50-fold larger than the icv dose of nitric oxide. These results suggest that azide lethality is due to enhanced excitatory transmission in the central nervous system perhaps after its conversion to nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute neurotoxicity of sodium azide and nitric oxide. 191 70

Like the anxiogenic drugs caffeine, pentylenetetrazole, and yohimbine, the endogenous neuroactive monoamine beta-phenylethylamine (PEA) is effective in three tests for anxiogens in mice. In a social interaction test it reduced both the number and duration of contacts. In a conflict situation test (a dark-light chamber) it reduced the number of transitions between dark and light compartments. Diazepam, a standard anxiolytic, prevented both effects of PEA. Intracerebroventricular administration of PEA induced generalized clonic seizures which were antagonized by various anxiolytics but not by the tested doses of butyrophenone neuroleptics and standard anticonvulsants effective in other tests for convulsants.
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PMID:Beta-phenylethylamine (PEA): an endogenous anxiogen? Three series of experimental data. 198 Apr 22

Insulin has recently been shown experimentally to modify ischemic brain damage when administered either before or after the episode of ischemia. In controlled studies in the rat, high doses of insulin (greater than or equal to 8 IU/kg) result in seizures and early death. The present study was undertaken to determine whether diazepam, a potent, centrally penetrating GABAmimetic, alone or in combination with insulin, could mitigate postischemic seizures or regional selective neuronal necrosis and infarction. Forebrain ischemia was induced in rats for 10 1/2 minutes by carotid clamping and hypotension. The animals were observed clinically until elective perfusion-fixation and quantitative pathologic examination at 1-week recovery. Diazepam, either alone or with insulin, reduced regional brain necrosis and reduced the seizure rate. Insulin alone also led to reduced regional necrosis. However, the combination of diazepam plus insulin yielded the greatest proportion of undamaged brains in the hippocampus, thalamus, and midbrain. In the neocortex, the diazepam-only group showed the greatest number of normal hemispheres. Hypothalamic infarction was eliminated by all three treatments. Seizures per se were associated with increased damage in the cerebral cortex, thalamus, and brainstem, irrespective of treatment group. The findings indicate that ischemic brain necrosis can be mitigated by diazepam and insulin treatment begun in the immediate postischemic period.
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PMID:Postischemic seizures and necrotizing ischemic brain damage: neuroprotective effect of postischemic diazepam and insulin. 200 13

The effect of diazepam, haloperidol, MK-801, and propranolol in antagonizing behavioral symptoms induced by lethal doses of cocaine, amphetamine, and methamphetamine were studied in a rat model. Animals were first pretreated IP with potential antagonists, diazepam (2, 5, and 10 mg/kg), haloperidol (5, 10, and 20 mg/kg), propranolol (5, 10, and 20 mg/kg), MK-801 (0.5, 1.0, and 2.5 mg/kg), and then were challenged IP with cocaine (70 mg/kg) (LD85), d-amphetamine (75 mg/kg) (LD100), and methamphetamine (100 mg/kg) (LD90). Diazepam, at all doses, provided significant protection against cocaine- (p less than or equal to 0.01) and methamphetamine- (p less than or equal to 0.05) induced seizures and produced a dose-dependent effect against amphetamine-induced seizures. MK-801, at all doses, reduced seizures in all groups (p less than or equal to 0.01). Propranolol altered the incidence of methamphetamine-induced seizures. Significant protection against cocaine-induced death was afforded by diazepam (p less than or equal to 0.01) and propranolol (p less than or equal to 0.05). Significant protection against amphetamine-induced death was provided by haloperidol (all doses, p less than or equal to 0.1), MK-801 (all doses, p less than or equal to 0.1), and propranolol (10 and 20 mg/kg, p less than or equal to 0.1). No agent reduced the incidence of methamphetamine- (50 or 100 mg/kg) induced death. The failure of d-amphetamine antagonists to protect against methamphetamine-induced toxicity and death suggest that different mechanisms of toxicity may exist between these drugs.
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PMID:Antagonism of cocaine, amphetamine, and methamphetamine toxicity. 221

The neurologic complications of cocaine toxicity are responsible for a major portion of the morbidity and mortality associated with cocaine. Most of the complications appear to be related to the hyperadrenergic state induced by cocaine and may be treated symptomatically. Diazepam is the most effective drug for cocaine-induced seizures.
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PMID:Neurologic complications of cocaine abuse. 153 80

The possibility to elicit convulsions in rabbits after flunarizine, iv was investigated. A flunarizine solution, 3.3 mg/ml, was given iv at a rate of 1.5 ml/min in three fractional doses every 30 min. Action of anti-epileptic drugs in seizures induced by flunarizine was additionally examined. Convulsive seizures occurred 2-10 min after the last successive dose of flunarizine as alternating clonic and tonic seizures. A treatment with anti-epileptic drugs showed that both phenobarbital at doses 6, 7 and 7.5 mg/kg iv and pentobarbital at doses of 15, 20 and 25 mg/kg, iv did not entirely suppress convulsive seizures, although convulsive episodes were rare. Diazepam at doses of 1-1.5 mg/kg, iv suppressed convulsive seizures.
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PMID:Intravenous injection of flunarizine elicits epileptiform convulsions. Preliminary evaluation of anti-epileptic drugs. 227 68

The efficacy of diazepam, haloperidol, propranolol, and yohimbine in antagonizing the toxic manifestations of d-amphetamine were studied in rats. In the control group of animals given 75 mg/kg intraperitoneal (ip) d-amphetamine, 95% developed seizures, and 100% died in mean times of 12.6 +/- 1.0 and 50.1 +/- 5.9 minutes, respectively. Significant protection against d-amphetamine-induced death was afforded by pretreatment with haloperidol (1.0 to 20.0 mg/kg) or propranolol (20.0 to 30.0 mg/kg). Diazepam (5.0 to 10.0 mg/kg) significantly reduced the incidence of clinically overt seizures but offered no protection against death. Yohimbine (2.5 to 10.0 mg/kg) was ineffective in preventing either seizures or death. When haloperidol (1.0 mg/kg) was administered in combination with diazepam (2.0 mg/kg), the incidence of death was no different than if haloperidol were given alone. In combination, haloperidol (1.0 mg/kg) and propranolol (10.0 mg/kg) reduced death more than either agent alone. These data support a protective role of haloperidol or propranolol in the treatment of d-amphetamine intoxication and show no protection with diazepam or yohimbine.
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PMID:Protection against d-amphetamine toxicity. 230 76

The amygdaloid kindling phenomenon has been widely used to evaluate and screen potential anticonvulsant compounds in adult rats. In the current study, weanling rats (ages 23-25 days) were implanted chronically with amygdaloid electrodes. They were treated with dimethylsulfoxide (DMSO), 0.5 mg/kg diazepam or 1.0 mg/kg diazepam before twice daily kindling stimulations to determine the effect of diazepam on the acquisition of the kindled seizure. Additional juvenile rats implanted as weanlings and simulated twice daily without drug pretreatment until fully kindled were used to test for the acute anticonvulsant effects of diazepam (0.25-4.0 mg/kg). Diazepam was demonstrated to have anticonvulsant properties in juvenile rats by both prolonging the time to develop the fully kindled response during acquisition and by reducing the elicited seizure severity and the length of the afterdischarge in the fully kindled juvenile rats. Together, these data point to the extension of the anticonvulsant profile of diazepam to now include juvenile amygdaloid kindling in rats. They further point to the potential ability of screening proposed anticonvulsant drugs for their efficacy against amygdaloid kindling in immature rats.
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PMID:Modification of amygdaloid kindling by diazepam in juvenile rats. 232 33

A model of partial complex (limbic) seizures in the anesthetized rat based on the phenomenon of maximal dentate activation was used to study the effect of various known antiepileptic drugs. Maximal dentate activation consists of a distinct triad of large amplitude population spikes, associated with a rise in [K+]0 to 10 mM and a negative shift of the DC potential. Repeated stimulation produces lengthening of the duration of maximal dentate activation (mimicking the lengthening of afterdischarges that occurs during kindling) and a decrease in the time to onset of maximal dentate activation. Diazepam (3 mg/kg), carbamazepine (50 mg/kg) and phenobarbital (60 mg/kg) caused a reversible reduction in the duration of maximal dentate activation. Carbamazepine (30 mg/kg) and phenobarbital (20 mg/kg) prevented the lengthening of maximal dentate activation that occurs with repeated elicitation while phenytoin (80 mg/kg), ethosuximide (300 mg/kg) and valproic acid (300 mg/kg) had no effect. The doses of these known antiepileptic drugs agree with the doses efficacious against limbic seizures in awake rats. This suggests that the ability to shorten the duration of maximal dentate activation provides a useful means to screen compounds for activity against partial complex seizures.
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PMID:Maximal dentate activation: a tool to screen compounds for activity against limbic seizures. 238 73


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