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)

Propofol, the relatively new, short-acting general anesthetic, markedly enhances the action of GABA at the GABAA receptor. To evaluate its effects on field potentials evoked in the dentate gyrus (DG) during the anesthetic and recovery periods, propofol was administered intraperitoneally to behaving rats bearing stimulating electrodes in the dorsal perforant path (DPP), where medial perforant path fibers predominate, and in the anterior piriform cortex (PC; i.e., olfactory cortex), and recording electrodes in the DG. Input from the PC reaches the DG via the lateral perforant path. Population slow waves (SWs) were evoked by paired-pulse stimulation of the PC at a 32 ms interstimulus interval (ISI) to produce paired-pulse facilitation in the awake animal. We had previously demonstrated that amplitude of SW2 (produced by the second stimulus) was greatly decreased by GABAergic drugs and increased by antiGABAergic convulsant agents. After administration of propofol, mean amplitude of SW2 decreased immediately and remained low for 30-60 min during propofol-induced sleep (as expected), then unexpectedly increased to about 1.5- to 2-fold above pretreatment levels at 2-4 h before gradually returning to pretreatment levels. In addition, the DPP was stimulated to produce either paired-pulse inhibition (20 ms ISI) or facilitation (32 ms ISI) of DG population spikes (PSs) in the awake animal. PS2 was much more inhibited during propofol-induced sleep, than during the pretreatment period, consistent with an expected marked increase in recurrent inhibition. An overshoot in PS2 amplitude was observed only occasionally during recovery, suggesting that withdrawal overshoot in amplitudes is more characteristic of PC-evoked DG SW2 potentials. The overshoot in SW2 amplitude during recovery may have been related to propofol's 'rapid on-rapid off' actions on the GABAA receptor, perhaps resulting in a phenomenon like the 'GABA withdrawal syndrome'. Such an effect, if true, may help explain the rare occurrence of seizures, especially during recovery, associated with its use clinically.
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PMID:The short-acting anesthetic propofol produces biphasic effects-depression and withdrawal rebound overshoot-on some (but not all) limbic evoked potentials in the behaving rat. 991 37

1. Several derivatives and analogues of the general anaesthetic 2,6-diisopropylphenol (propofol) have been recently synthesised with the aim of exploring the structure-activity relationships. 2. In the present study, the effects of one such compound, 4-iodo-2,6-diisopropylphenol (4-I-Pro), on gamma-aminobutyric acid type A (GABA(A)) receptors in vitro were compared with its in vivo effects in rodents. Human GABA(A) receptors were expressed in Xenopus oocytes, and the actions of 4-I-Pro on receptor function were compared with those of propofol by two-electrode voltage-clamp recording. 3. Similar to propofol, 4-I-Pro directly activated Cl- currents in the absence of GABA at all combinations of receptor subunits tested. However, the efficacy of 4-I-Pro in inducing direct activation of alpha1beta2gamma2S receptors was markedly less than that of propofol. 4. Similarly to propofol, 4-I-Pro potentiated in a concentration-dependent manner GABA-evoked Cl- currents measured at different GABA(A) receptor constructs. 5. As expected, intraperitoneal injection of propofol induced sedation, ataxia, and loss of the righting reflex in rats. In contrast, administration of 4-I-Pro failed to produce any of these behavioural effects. 6. Administration of 4-I-Pro to rats reduced in a dose-dependent manner the incidence of tonic-clonic seizures induced by pentylenetetrazol and induced an anticonflict effect as measured in the Vogel test. 7. Microdialysis revealed that, like propofol, administration of 4-I-Pro reduced acetylcholine release in the hippocampus of freely moving rats. 8. These results demonstrate that para-substitution of the phenol ring of propofol with iodine yields a compound that exhibits anticonvulsant and anticonflict effects, but is devoid of sedative-hypnotic and anaesthetic properties. Thus, 4-I-Pro possesses pharmacological characteristics more similar to anxiolytic and anticonvulsant drugs than to general anaesthetics.
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PMID:Characterization of the electrophysiological and pharmacological effects of 4-iodo-2,6-diisopropylphenol, a propofol analogue devoid of sedative-anaesthetic properties. 1021 39

Propofol has been proposed as a sedative agent during awake craniotomies. However, there are reports of propofol suppressing spontaneous epileptiform electrocorticography (ECoG) activity during seizure surgery, while others describe propofol-induced epileptiform activity. The purpose of this study was to determine if propofol interferes with ECoG and direct cortical stimulation during awake craniotomies in children. Children scheduled for awake craniotomies for resection of epileptic foci or tumours were studied. An intravenous bolus of 1-2 mg.kg-1 followed by infusion of 100-200 microgram.kg-1.min-1 of propofol was administered to induce unconsciousness. Fentanyl (0.5 microgram.kg-1) was administered incrementally to provide analgesia. After the cortex was exposed, the propofol infusion was stopped and the patient permitted to awaken. Cortical electrodes were applied. ECoG was recorded continuously on a Grass polygraph. Motor, sensory, language, and memory testing were done throughout the procedure. The cortex was stimulated with a hand-held electrode using sequential increases in voltage to map the relevant speech and motor areas. We studied 12 children (aged 11-15 years) with intractable seizures. The raw ECoG did not reveal any prolonged beta-waves associated with propofol effect. Electroencephalogram spikes due to spontaneous activity or cortical stimulation were easily detected. Cognitive, memory and speech testing was also successful. We conclude that propofol did not interfere with intraoperative ECoG during awake craniotomies. Using this technique, we were able to fully assess motor, sensory, cognitive, speech and memory function and simultaneously avoid routine airway manipulation.
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PMID:The effect of propofol on intraoperative electrocorticography and cortical stimulation during awake craniotomies in children. 1063 6

The effects of different doses of propofol on post-electroconvulsive therapy (ECT) cognitive recovery were evaluated together with the effects on seizure duration and hemodynamic changes during ECT in 15 depressive patients. Propofol attenuated the increase in arterial blood pressure and heart rate in a dose-dependent manner compared with thiamylal. Propofol showed a clinically significant anticonvulsant effect during ECT in a dose-dependent manner. There were no significant differences among the four different induction groups in the mean recovery time from anesthesia, however, a low dose of propofol suppressed the early recovery of cognitive function. For early cognitive recovery after ECT, a deep anesthetic level is necessary when the traditional ECT apparatus is used which produces sine curve wave stimuli.
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PMID:Effects of propofol anesthesia on cognitive recovery of patients undergoing electroconvulsive therapy. 1068 46

Propofol provokes a slight hypotensive effect that could mitigate the cardiovascular response to electroconvulsive therapy (ECT). In this study we compared the effects of propofol and thiopental for ECT anesthesia in seven women (22-67 years of age). Anesthesia was induced with either thiopental or propofol, and with atropine and suxamethonium for each treatment. The first anesthesia was assigned to thiopental or propofol at random; the next anesthesia was induced with the other drug, and alternated thereafter. Systolic blood pressure, diastolic blood pressure (DBP), and heart rate (HR) were recorded before anesthesia, after anesthetic induction, and 1 and 5 min after ECT. ECT-induced increases in DBP and HR were less marked with propofol than with thiopental. Seizure durations were decreased with propofol compared with thiopental.
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PMID:Cardiovascular Response and Anesthetic Recovery in Electroconvulsive Therapy with Propofol or Thiopental. 1194 Nov 99

Ketamine, etomidate and propofol modified behavioral and electrographic correlates of kindled seizures in rats. In detail, ketamine (5 mg/kg) and propofol (15 mg/kg) significantly increased afterdischarge threshold, reduced seizure severity and shortened seizure and afterdischarge durations. Etomidate (7.5 mg/kg) was effective in terms of seizure and afterdischarge durations. Moreover, the combinations of ketamine (2.5 mg/kg) with carbamazepine (15 mg/kg) or valproate (50 mg/kg; all drugs at their subeffective doses), reduced the severity and duration of kindled seizures. The antiseizure potency of the ketamine/carbamazepine combination was comparable to that of carbamazepine alone administered at 20 mg/kg, while the effect of ketamine/valproate was comparable to the efficacy of valproate alone at 100 mg/kg. However, the combinations of ketamine with phenobarbital or diphenylhydantoin did not exert any protective action. Propofol and etomidate entirely failed to interact with conventional antiepileptics. The combinations of ketamine with carbamazepine or valproate did not induce any significant motor impairment in the chimney test or memory deficit in the passive avoidance task. A pharmacokinetic interaction, at least in plasma, can be excluded, because ketamine (2.5 mg/kg) did not affect the free plasma concentrations of carbamazepine or valproate. Results of the present study may suggest that there may be no risk of negative interactions between injectable anesthetics and antiepileptics in cases of partial epilepsy.
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PMID:Effects of etomidate, ketamine or propofol, and their combinations with conventional antiepileptic drugs on amygdala-kindled convulsions in rats. 1287 49

Electroconvulsive therapy is an effective treatment for severe and medication-resistant depression. There have been no reports describing how a volatile anaesthetic affects haemodynamic responses, seizure duration, and recovery characteristics during electroconvulsive therapy. We carried out a repeated-measure crossover study to compare the effects on haemodynamic responses, seizure duration, and recovery characteristics of the following types of anaesthesia in electroconvulsive therapy: propofol alone, sevoflurane alone, and propofol combined with sevoflurane. We recruited 50 patients requiring electroconvulsive therapy for depression. For anaesthesia induction, 1.5 mg/kg propofol (condition P), 5% sevoflurane in oxygen following a vital capacity rapid inhalation induction (condition S), or 1.5 mg/kg propofol followed by 5% sevoflurane in oxygen (condition PS) was administered. Succinylcholine 1.5 mg/kg was then given. Electrical stimulation was administered after fasciculation. Measurements were obtained before anaesthesia induction (baseline), prior to succinylcholine administration, prior to electroconvulsive therapy, and at the peak after electroconvulsive therapy. After electroconvulsive therapy, peak heart rate and peak mean arterial pressure were highest in condition S. Whereas recovery time was longest in condition PS, motor seizure duration was significantly shorter than in either condition P or S. Electroencephalographic seizure duration was significantly shorter in condition PS than in condition P and significantly shorter in condition S than in condition P. Sevoflurane anaesthesia alone is most disadvantageous in terms of haemodynamics. Propofol-sevoflurane anaesthesia is advantageous in terms of haemodynamics, but disadvantageous in terms of seizure duration and recovery time. Propofol alone is most advantageous in terms of seizure duration.
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PMID:Propofol alone, sevoflurane alone, and combined propofol-sevoflurane anaesthesia in electroconvulsive therapy. 1297 63

Propofol was reported to exhibit an antiepileptic activity. This study was performed to investigate the effect of propofol on evoked and spontaneous seizure-like activity induced by the convulsant veratridine. Studies were performed on rat brain slices using conventional electrophysiological intracellular techniques. The alteration of sodium channel function by veratridine (0.3 microM) induced an evoked and spontaneous seizure-like activity in the hippocampal CA1 pyramidal neurons. Therapeutic concentrations of propofol (10 microM) were ineffective in inhibiting veratridine-induced seizure-like activity. However, higher concentrations (50-100 microM, n=6) inhibited both evoked and spontaneous bursting, induced by veratridine. The inhibitory effect of propofol (100 microM) was associated with membrane hyperpolarization [after veratridine, -66+/-0.71 mV (mean+/-S.E.M.), and after propofol, -77+/-2.15 mV] and with an increase in input resistance [after veratridine (37.8+/-1.2 MOmega) and after propofol (43+/-1.3 MOmega)]. The drug also produced an increase in current threshold. Results from this study are valuable in solving critical questions regarding the antiepileptic activity of propofol and strengthen the validity of the veratridine model in testing for potential antiepileptic drugs.
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PMID:Propofol exhibits antiepileptic activity in hippocampal pyramidal neurons. 1500 71

Propofol has been used to treat convulsions, while the drug is known to induce convulsions. We described a case of generalized convulsions during brain tumor resection under propofol anesthesia. A 24-year-old man was scheduled to undergo brain tumor resection. He had no history of epilepsy. Anesthesia was induced and maintained with propofol and fentanyl. During the craniotomy, the patient developed generalized convulsions. Diazepam, thiamylal, and phenytoin were given intravenously and the seizure activity resolved. Generalized convulsions recurred three times during the operation. Postoperative course was uneventful. On the 16 th postoperative day, the patient underwent ventriculoperitoneal shunt under general anesthesia using sevoflurane, nitrous oxide and oxygen. Convulsions were not noted intra- and postoperatively. Because convulsions did not occur during sevoflurane anesthesia and the patient had no history of epilepsy, propofol may have induced a generalized convulsions on the first operation.
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PMID:[Refractory generalized convulsions in a patient undergoing brain tumor resection during propofol anesthesia]. 1524 47

Propofol is used for the treatment of refractory status epilepticus. When given as a long-term infusion propofol may cause a rare but frequently fatal complication, the propofol infusion syndrome. The hallmarks are metabolic acidosis, lipemia, rhabdomyolysis and myocardial failure. Propofol infusion syndrome is caused by impaired fatty acid oxidation. Beside anticonvulsants the ketogenic diet, a high-fat, low-carbohydrate, adequate-protein diet, is an effective treatment for difficult-to-control seizures. We report a 10-year-old boy with catastrophic epilepsy, who developed fatal propofol infusion syndrome when a ketogenic diet was initiated. Substances like propofol which impair fatty acid oxidation may pose an increased risk if combined with ketogenic diet.
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PMID:Fatal propofol infusion syndrome in association with ketogenic diet. 1532 67


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