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)

We have investigated the pharmacological basis of CNS excitation that occurs in association with general anaesthesia in mice. Propofol produced sustained clonic movements during anaesthesia. Methohexitone produced intermittent non-rhythmic jerking during anaesthesia. Ethanol and pentobarbitone produced anaesthesia without associated clonic movements. Doses of all anaesthetic drugs were equipotent. Surface EEG recordings showed paroxysmal discharges consistent with interictal manifestations of cortical seizures with methohexitone or propofol, but not with ethanol or pentobarbitone. Strychnine, a glycine antagonist without effects on the cerebral cortex, and bicuculline, a GABAA antagonist with effects on the cerebral cortex, were used in doses that were equipotent-0.5 log units less than the ED10 for clonic convulsions. Strychnine potentiated both excitatory behaviour and EEG paroxysmal discharges when given with methohexitone or propofol, but not with ethanol or pentobarbitone. Bicuculline did not affect either behaviour or EEG with any of the anaesthetic drugs. Our data show that methohexitone and propofol produced CNS excitation, while pentobarbitone and ethanol did not. We propose that the pharmacological basis of this excitation may be glycine antagonism occurring in subcortical structures.
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PMID:Does glycine antagonism underlie the excitatory effects of methohexitone and propofol? 164 44

Perioperative seizures have numerous potential etiologies. In general, when seizures occur during surgery, their onset often coincides with the introduction of a specific anesthetic or analgesic drug. Conversely, postoperative seizures are more commonly due to nonanesthetic causes. However, there have been reports of postoperative convulsions that appeared to be caused by anesthetic or analgesic drugs administered intraoperatively via inhalation or injection (e.g., intravenous, epidural, or peripheral nerve block). Some anesthetics appear to possess both proconvulsant and anticonvulsant properties. One possible factor is an inherent pharmacodynamic variability in the responsiveness of inhibitory and excitatory target tissues in the CNS. This is well illustrated by the anticonvulsant and proconvulsant effects of progressively higher doses of local anesthetic drugs. This variability in neuronal responsiveness could also explain the conflicting findings for low versus high doses of fentanyl and etomidate. Furthermore, biological variation in the individual patient's responsiveness to certain anesthetic drugs could be an additional contributory factor. Differing structure-activity relationships might also explain why some anesthetic agents possess both proconvulsant and anticonvulsant properties. Relatively minor modifications in a drug's structure can influence its affinity for a specific receptor site and its intrinsic pharmacologic activity. For example, when methohexital was first introduced, convulsions were commonly encountered in patients with and without a history of epilepsy. Subsequent fractionation of the original compound into its two isomeric forms resulted in the identification of the isomer primarily responsible for this convulsive activity. In its present formulation (Brevital; Eli Lilly, Indianapolis, Ind.), the epileptogenic properties of methohexital are limited to patients with psychomotor epilepsy. However, compared with thiopental, excitatory effects are still more common with methohexital. The excitatory effects of methohexital are presumably due to its methylated structure. The inhaled anesthetic flurothyl (hexaflurodiethyl) ether and the intravenous anesthetic ketamine also illustrate how subtle changes in stereoisomerism can result in significant changes in structure-activity relationships. Flurothyl, a fluorinated ether analogue, reliably produces convulsions in nonepileptic patients, whereas its structural isomer isoindoklon has not been associated with seizure activity. Other examples of isomer or structural analogue relationships that produce differential effects on neuronal hyperexcitability include enflurane-isoflurane and meperidine-normeperidine. In conclusion, the patient population (epileptic or nonepileptic), the method of documentation (EEG study or clinical observation), and the method of EEG analysis (cortical or depth electrodes) must be considered to properly analyze the proconvulsant and/or anticonvulsant properties of an anesthetic or analgesic drug.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pro- and anticonvulsant effects of anesthetics (Part II) 240 Jan 25

Intravenous (i.v.) methohexital (MTH, Brevital) was found to have an effect on the intraoperative electrocorticogram (ECOG) of 63 patients who had temporal lobectomies performed under general anesthesia for intractable complex partial seizures. In the preresection ECOG, MTH increased the frequency of spikes in 78%, the area of cortical spiking in 30% and induced seemingly "new" spike foci in 43%. Similar although less dramatic changes occurred in the final (i.e., postresection) ECOG. Whether these changes induced by MTH, specifically the new spike foci, are significant was assessed by correlating surgical results with the presence of "residual spikes" (i.e., after all resections, not spontaneously occurring but activated by MTH). Surprisingly, nine patients with residual "MTH-spikes" did not have any postoperative seizures whereas two had some. This raises the question of whether MTH effects are significant overall. Caution is advised in the use of MTH in intraoperative assessment of interictal spike fields, especially when new spike foci are activated. Further study of the possibility of false activation, with a larger series, is advised.
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PMID:Methohexital (Brevital) effect on electrocorticogram may be misleading. 240 Dec 45

Eleven SEEG investigations were analysed in patients with temporal epilepsy after separate intravenous injection of Brietal and gamma-OH. The authors discuss a modification of the background activity and pathological seizure discharges in the cortex and deep structures of the temporal lobes. Attention is called to an evident increase of the quantitative and qualitative elements of excitation or manifestation of seizure activity not present previously. The activating effect of the these preparations on the pathological bioelectric activity without presence of clinically observable seizures suggests the possibility of existence of inhibitory mechanisms at the levels below the cortex and limbic system, probably in the reticular system of the brain stem. It was found that in the used doses the administration of both preparations was completely safe. Brietal and gamma-OH are good preparations facilitating more accurate diagnosis of epilepsy.
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PMID:[Effect of brietal and gamma-OH on the bioelectric activity of the cerebral cortex and deep temporal structures in SEEG studies in patients with epilepsy]. 663 98

45 cases of partial seizures of temporal lobe origin undergoing sequential EEG investigation first with routine and then methohexitone activated EEG, 31 supplemented by sphenoidal electrodes, are reported. Methohexitone activated foci from temporal lobes which had previously not displayed temporal spike or sharp wave discharges in 15 (33.3%) cases. In 11 (24.4%) this was the first evidence of the focus in 15 (33.3%) cases. In 11 (24.8%) this was the first evidence of the focus in either temporal lobe and in 4 (8.9%) the focus was contralateral to one already seen in routine EEG. In 3 (6.7%) cases the sphenoidal electrodes were essential for demonstrating the focus. Methohexitone evoked temporal spikes or sharp waves irrespective of the nature of the initial routine EEG which was either normal, had non "epileptic" temporal abnormalities or abnormalities outside the temporal region. 2 X 2 chi 2 tests, comparing the frequency with which a particular symptom was accompanied by an EEG in a sequence with temporal discharges, showed that only in the case of evolution to generalised tonic/clonic seizures (secondary generalization) was the association statistically significant: chi 2 4.28, P less than 0.025. Similar testing of length of history and frequency of attacks against the frequency with which temporal discharges occurred failed to establish a statistically significant association.
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PMID:Sequential EEG findings and symptoms in partial seizures of temporal lobe origin. 713 92

Computer assisted energy-spectral analyses were obtained on EEG recordings of unilateral non-dominant hemisphere ECT-induced seizures using the different pre-ECT anesthetic agents methohexital (Brevital), Innovar, and ketamine (Ketalar). The previously postulated predominance of electrical energy over the stimulated (right) hemisphere early in ECT-induced seizures is confirmed. There appears to be marked reduction in total seizure energy with methohexital anesthesia, whereas ketamine anesthesia appears to be associated with increased overall seizure energy. The greatest right to left energy transfer during the seizure occurred with Innovar anesthesia.
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PMID:The electroencephalographic pattern during electroconvulsive therapy II. Preliminary analysis of spectral energy. 717 56

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