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)

The cardiopulmonary consequences of diazepam (0.5 mg/kg, IV) followed by ketamine (10 mg/kg, IV) were evaluated in 11 dogs. Diazepam did not exhibit a tranquilizing effect and was frequently associated with excessive excitement. It produced minimal cardiopulmonary effects, except for a significant increase in heart rate. Ketamine administration was associated with less cardiovascular stimulation when administered after diazepam than it did when administered alone; the respiratory depression was greater. Compared with ketamine alone, the diazepam-ketamine combination was associated with more vomition, less muscle hypertonus, less seizure activity, and less salivation.
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PMID:Cardiovascular changes in dogs given diazepam and diazepam-ketamine. 308 35

The role of excitatory amino acid neurotransmission in epileptogenesis was investigated in the developing hippocampus. Bath application of ketamine blocked penicillin-induced, synchronized afterdischarges in immature rat CA3 hippocampal neurons. Ketamine also decreased the duration of the preceding intracellularly recorded depolarization shift but had no measurable effect on the resting membrane potential or input impedance of pyramidal cells. Concentrations of ketamine that blocked afterdischarge generation dramatically depressed intracellular depolarizations produced by iontophoretic application of N-methyl-D-aspartate (NMDA) but not quisqualate. The effects of the NMDA antagonist 2-amino-7-phosphonoheptanoic acid on epileptiform discharges were identical to those of ketamine. These results suggest that an endogenous excitatory amino acid acting on an NMDA receptor plays a key role in the pronounced capacity of immature hippocampus for seizures.
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PMID:Ketamine selectively suppresses synchronized afterdischarges in immature hippocampus. 353 27

The pro- and anticonvulsant effects of phencyclidine (1-[1-phenylcyclohexyl]piperidine HCl, PCP), a number of its analogues, and SKF 10047 were investigated in rats. The PCP analogues were compounds produced by substitutions for the phenyl and piperidine rings of PCP and were selected to elucidate the structure-activity relationships existing between PCP and its pro- and/or anticonvulsant effects. All of the compounds, except ketamine, induced convulsions at high (12.8-25.6 mg/kg, i.v.), yet almost always sublethal doses. Ketamine failed to induce convulsions, even at lethal doses (51.2 mg/kg, i.v.). The acute pro- or anticonvulsant actions of PCP were then investigated. Rats were subjected to transorbital electroconvulsive shock subsequent to i.p. injections of saline or 0.625, 2.5, 5.0, 10.0 or 20.0 mg/kg PCP. It was found that PCP induced an acute, dose-dependent anticonvulsant effect. The acute pro- and/or anticonvulsant actions of the remaining compounds were then investigated by administration of electroconvulsive shock subsequent to i.p. injections of saline or one of two doses of each compound. The low and high doses of each compound were selected to be behaviorally equivalent to 2.5 and 10.0 mg/kg PCP i.p., respectively. With one exception, each dose of each drug induced an acute anticonvulsant action, with no difference in efficacy between the compounds tested. However, PCA (produced by substitution of an amine for the piperidine ring of PCP) induced a statistically greater anticonvulsant action at the higher, compared to the lower, dose. In addition, PCA was the only compound to eliminate all motor signs of the electrically induced seizure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The convulsant and anticonvulsant effects of phencyclidine (PCP) and PCP analogues in the rat. 396 7

Ketamine produces both excitatory and depressant actions in the brain, but there have been conflicting results regarding which structures are affected and the magnitude of the alteration in cerebral metabolism produced. The authors applied the 2-[14C]deoxyglucose method quantitatively to a study of ketamine anesthesia (10 or 30 mg/kg intravenously) in the rat. Ketamine caused both increases and decreases in local cerebral glucose utilization. The areas with altered glucose utilization could be grouped into functional systems. Some structures of the limbic system showed large increases in glucose utilization; indeed the 70 per cent increases in cingulate gyrus and hippocampus were the largest of all regions examined. The extrapyramidal motor system and corpus callosum showed significant but less dramatic (20-40 per cent) increases. On the other hand, decreased metabolism occurred in the somatosensory and auditory systems, with the greatest reduction (40 per cent) in the inferior colliculus. Within some structures, such as the caudate nucleus and visual cortex, a striking redistribution of metabolism which is characterized by a change in the autoradiographic pattern of activity was noted. Reduced glucose utilization in the somatosensory and auditory systems suggests that a selective sensory deprivation occurs during ketamine anesthesia while the increased metabolism in the limbic system is consistent with neurophysiologic studies which have demonstrated seizure activity in this region. Compared with other anesthetics, which tend to produce a generalized decrease in metabolism, the cerebral metabolic effects of ketamine are unique and emphasize that it produces a state of "anesthesia" which is quite different from that of other commonly used drugs.
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PMID:Local changes in cerebral glucose utilization during ketamine anesthesia. 708 28

The anesthetic agents methohexital (Brevital), Innovar, and ketamine (Ketaject) were examined for their effect on seizure duration following electroconvulsive stimulation in a rat model of electroconvulsive therapy (ECT). Compared to unanesthetized control animals, methohexital anesthesia shortened seizure duration by 42%, ketamine anesthesia tended to increase seizure duration, and Innovar anesthesia had no effect on duration of seizures.
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PMID:Anesthetics and electroconvulsive therapy seizure duration: implications for therapy from a rat model. 734 26

Ketamine appears to induce both excitatory and depressant actions in the brain; however, it is not clear which regions are affected. The 2-deoxyglucose functional mapping method of Sokoloff et al. was used to determine regional variations in metabolic activity of rat brain caused by injection of ketamine, 25-75 mg, intramuscularly. To compare the effects of ketamine with those of hippocampal-induced seizures, the 2-deoxyglucose method was used, following injection of penicillin G, 400-800 units, into the hippocampus. The findings from five control, seven ketamine-treated, and three penicillin G-treated rats are given. Ketamine caused a significant increase of metabolic activity in the hippocampal sulci and a decrease of activity in the medial geniculate and the inferior colliculus. Similar changes were found with hippocampal seizures caused by penicillin. The inhibition of the regions associated with sensory systems (medial geniculate and inferior colliculus) may account in part for the anesthetic action of ketamine, while the intense activity of the hippocampus may be related to the excitatory manifestations. The results indicate that ketamine produces seizures in the hippocampus, which in turn inhibit auditory and visually associated nuclei. Thus, the anesthesia may follow from the sensory depression and the cataleptic phenomena may be related to the hippocampal excitation.
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PMID:Ketamine-induced changes in regional glucose utilization in the rat brain. 736 54

Action of ketamine (5-40 mg/kg) was tested against electrically induced hippocampal afterdischarges (four stimulations in one session; 8 Hz, 15 s) in rats 7, 12, 18, 25 and 90 days old. In control sessions, there was either stable afterdischarge (AD) duration and wet dog shakes (WDS) number or there was an increase in ADs' duration with repeated stimulations. Ketamine had dose-dependent and age-dependent effects. In 7-18-day-old rats, ketamine suppressed better WDS number than AD duration, with nearly absent action on AD duration in 18-day-old animals. Ketamine was equipotent for both phenomena in 25-day-old rats and, in contrast, it decreased more AD duration than WDS number in 90-day-old rats. The data suggest a differentiation induced by ketamine in the expression of motor and electrographic phenomena of the experimental seizures.
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PMID:Developmental changes of ketamine action against epileptic afterdischarges induced by hippocampal stimulation in rats. 780 75

We investigated the neuroprotective effect of the noncompetitive N-methyl-D-asparatate (NMDA) antagonist ketamine when administered after onset of lithium-pilocarpine-induced status epilepticus (SE). Seizures were induced in Wistar rats with lithium chloride (3 mEq/kg) and pilocarpine (PC) (30-60 mg/kg intraperitoneally, i.p.). Fifteen minutes after SE onset, either ketamine 100 mg/kg or normal saline was injected i.p., and 3 h after SE onset atropine, diazepam (DZP), and phenobarbital (PB) were administered i.p. to terminate the seizures. Twenty-four hours later, rats underwent brain perfusion-fixation, with subsequent brain processing for light-microscopic examination. Rats adminstered saline (n = 5) had neuronal damage in 24 of 25 brain regions examined. Rats administered ketamine (n = 7) had significant neuroprotection in 22 of 24 damaged regions. Ketamine reduced the amplitude of seizure discharges, and in 3 rats EEG seizure activity ceased in 30 min; none of these rats had neuronal damage. In the other 4 rats, EEG seizure discharges persisted > 90 min; in these animals, 21 of 24 damaged regions were protected. In contrast, rats with 1-h high-dose PC-induced SE (400 mg/kg i.p. without lithium chloride preadministration) had 14 damaged regions, of which 7 were significantly different from the undamaged regions of the ketamine subgroup with persistent electrographic seizures. Thus, ketamine is remarkably neuroprotective when administered after onset of SE, whether or not seizure discharges are eliminated.
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PMID:Neuroprotective effect of ketamine administered after status epilepticus onset. 782 Dec 77

Animal experimentation has revealed that ketamine has anticonvulsive properties. Changes in the EEG have also been reported in animals; these have been designated non-convulsive generalized electrographic seizures because of their similarities to epileptiform potentials, even though there are no recognizable signs of seizures. The cataleptic condition of the cats in which these changes were observed led to the conclusion that ketamine could cause petit mal seizures, which took the course of petit mal status. Ketamine was therefore also seen as a dangerous anaesthetic agent predisposing to convulsions, the use of which could lead to status epilepticus and irreversible brain damage. These conflicts of opinion should be resolved, as they are based on various misconceptions. (1) The terminology used for epilepsy by specialized clinicians is not always correctly applied in the context of animal experimentation. (2) The activation of epileptiform potentials in the EEG of animals cannot be interpreted as a reliable sign of epileptogenic efficiency in humans. (3) Too little regard is paid to the different actions of anaesthetic agents in various sites of the brain, at different doses and with different routes of administration. (4) The statistical significance and biological relevance of the study results are inadequate because the numbers of observations are too small. Epileptologists regret the insufficiency of animal models as paradigma for the study of efficiency of antiepileptic drugs in humans. The degree by which extensor spasms in the front paw of Gerbils of rats induced by pentylentetrazol or electric current are reduced after application of an anticonvulsive drug is no reliable measure of its anticonvulsive effect in humans.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Ketamine--anticonvulsive and proconvulsive actions]. 784 Apr 10

The potency of S-(+)-ketamine is approximately double that of the racemic ketamine. This study was carried out to investigate the recovery of cerebral electrical function after a bolus of 1.3 mg/kg ketamine or 0.65 mg/kg S-(+)-ketamine and subsequent continuous application of 4 mg/kg h ketamine per h or 2 mg/kg S-(+)-ketamine, per h for 15 min. Furthermore, the centrally acting, cholinergic agonist physostigmine has been reported to antagonize ketamine and to shorten the recovery period. Therefore, after S-(+)-ketamine 0.012 mg/kg physostigmine was tested against saline placebo. METHODS. With their own informed consent and the approval of the ethics committee 12 healthy volunteers were enrolled in a double-blind cross-over study. All drugs were dissolved in identical volumes. On three dates with intervals of at least 1 week between, ketamine/NaCl, S-(+)-ketamine/physostigmine or S-(+)-ketamine/NaCl was administered (Table 1). The sequence was randomized. The EEG was recorded from 20 sites according to the 10/20 system and after Fast-Fourier transformation computed into amplitudes within the delta, theta, alpha, and beta bands and within the total spectrum. The median, the spectral edge frequency and the dominant frequency (dF) were also determined. Mean values of all electrodes before and at 10, 15, 30, 45 and 195 min after the bolus injection were compared using two-dimensional analysis of variance (ANOVA, significance level P < 0.05). RESULTS. The characteristic increase in theta-amplitude and decrease of alpha-amplitude were observed after ketamine and S-(+)-ketamine. Median and dF dropped from the alpha to the theta frequency range. Ketamine led to a greater increase in total, delta, theta and beta amplitude during anaesthesia. 3 hours after ketamine/S-(+)-ketamine anaesthesia a significant decrease in the median and dominant frequency and in total, delta, theta, alpha and beta amplitudes confirmed residual impairment of cerebral function after all study drugs. No differences were found between physostigmine and placebo. DISCUSSION. The EEG changes during ketamine/S-(+)-ketamine administration suggest a slightly deeper anaesthetic level after ketamine. The course of recovery was not different after ketamine and after S-(+)-ketamine. The spectral edge frequency did not differ between measurement points, and is therefore not suitable for assessment of the depth of anaesthesia reached with ketamine/S-(+)-ketamine. The dose of physostigmine tested was probably too low to produce antagonism of S-(+)-ketamine. An increased dosage of physostigmine has yet to be studied, but is likely to cause a higher rate of side effects, such as nausea, vomiting and bradycardia, and possibly even tonic-clonic seizures.
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PMID:[Ketamine racemate versus S-(+)-ketamine with or without antagonism with physostigmine. A quantitative EEG study on volunteers]. 784 Apr 18


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