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

The present work deals with an EEG and behavioral study on the effects of carbamazepine (CBZ) and N6-L-phenylisopropyladenosine (L-PIA) against the convulsions due to caffeine and pentylenetetrazole (PTZ) in rabbits. Pretreatment with L-PIA (1, 3 and 4 mg/kg) caused a dose-related inhibition of the motor convulsions and the EEG "grand mal" ictal seizure induced by caffeine (75 mg/kg IV). On the contrary, L-PIA given at the high dose of 5 mg/kg IV partially inhibited the EEG and motor seizures elicited by PTZ (20 mg/kg IV). CBZ completely antagonized the EEG and motor convulsions induced by caffeine, while exerted only a protective action towards the EEG and motor convulsions due to PTZ. The administration of an ineffective dose of CBZ (5 mg/kg IV) was able to enhance the protective action of L-PIA towards caffeine-induced convulsions. This synergistic action between CBZ and L-PIA is also present towards the spike-and-wave complexes elicited by PTZ (10 mg/kg). These results confirm that the purinergic system plays an important role in the regulation of the CNS excitability. They suggest therefore, that the anticonvulsant properties of CBZ may be at least partially explained by an influence of this drug on the purinergic system.
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PMID:Anticonvulsant activity of carbamazepine and N6-L-phenylisopropyladenosine in rabbits. Relationship to adenosine receptors in central nervous system. 336 48

Seizures, often with fatal outcome, are a manifestation of pronounced theophylline intoxication. The purpose of this investigation was to characterize the relationship between theophylline concentrations and theophylline-induced convulsions and to develop an animal model suitable for exploring conditions that might predispose theophylline-treated individuals to seizures. Female Lewis rats (approximately 170 g) received an i.v. infusion of theophylline (as aminophylline) at one of three different rates (1.03-5.1 mg/min/rat) until the animals exhibited a maximal seizure (which occurred after 11 +/- 1 to 42 +/- 3 min of infusion). The total dose, the serum concentration (both total and unbound drug) and the brain concentration of theophylline at onset of seizures increased with increasing infusion rate. The theophylline concentration in cerebrospinal fluid at onset of seizures (mean +/- S.D., 232 +/- 17 mg/l, n = 41) was not affected by the infusion rate. The theophylline metabolites 1-methyluric acid and 1,3-dimethyluric acid were found in serum but at very much lower concentrations than those of theophylline. 1-Methylxanthine and caffeine were not detected in any serum sample, 3-methylxanthine was present in low concentrations in only some serum samples and 1-methyluric acid and 3-methylxanthine were found in the brain in low concentrations (less than 10 mg/kg). Theophylline metabolites were not detected in cerebrospinal fluid. Direct i.v. infusion of either 1-methyluric acid, 1,3-dimethyluric acid or 3-methylxanthine did not produce seizures despite high concentrations in serum. Ethylenediamine infusions also did not cause seizures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kinetics of drug action in disease states. XVI. Pharmacodynamics of theophylline-induced seizures in rats. 348 96

Several lines of evidence suggest that the convulsant actions of caffeine are mediated through benzodiazepine receptors. A pharmacogenetic approach has been used to further explore the relationship of these receptors to caffeine-induced seizures. The susceptibility of two inbred strains of mice (CBA and SWR) to the convulsant actions of picrotoxinin, strychnine, Ro 5-4864 and DMCM was examined. Previous studies have demonstrated these two strains differ in their susceptibilities to the convulsant action of caffeine. While no differences were observed between these two strains in susceptibility to tonic seizures induced by picrotoxinin, RO 5-4864 or strychnine, SWR mice were significantly less sensitive to tonic seizures induced by DMCM compared to CBA mice (CD50 values in CBA and SWR mice were 6 and 12 mg/kg IP). Both clonazepam and the benzodiazepine receptor antagonist, Ro 15-1788, significantly blocked caffeine-induced seizures. Further, when subconvulsant doses of caffeine and DMCM were combined, a synergistic action was observed. Taken together, these findings support the hypothesis that the convulsant actions of caffeine result from an action at benzodiazepine receptors, and that the hyporesponsiveness of the SWR strain to both caffeine- and DMCM-induced seizures could result from an inherited abnormality in these sites.
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PMID:Coincidence of seizure susceptibility to caffeine and to the benzodiazepine inverse agonist, DMCM, in SWR and CBA inbred mice. 357 58

Twenty-five evaluable patients with gliomas were treated with a combination of cytosine arabinoside plus cisplatin administered intravenously (IV). Ten of the 25 patients (40%) responded, including three of 13 patients (23%) with prior cranial radiation, and seven of 12 patients (58%) without prior cranial radiation. In a second study, intramuscular (IM) and oral caffeine were added to IV cytosine arabinoside plus cisplatin. Caffeine-induced seizures prevented escalation of the dose of caffeine to a level that would have been anticipated to potentiate the cytotoxicity of the cytosine arabinoside plus cisplatin. Twelve of 25 treated patients (48%) responded. Most of the patients had not received prior cranial radiation. In a third study, IV cytosine arabinoside was administered in combination with intracarotid and IV cisplatin, plus BCNU and tenoposide (VM-26). This study is continuing to accrue patients. Myelosuppression has been pronounced, but has generally been rapidly reversible. It is too early to comment on efficacy of this combination. Our results to date permit us to conclude that the combination of cytosine arabinoside plus cisplatin is capable of inducing regression of gliomas in some patients. We feel that further studies are warranted.
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PMID:Cytosine arabinoside plus cisplatin and other drugs as chemotherapy for gliomas. 358 85

During a course of ECT, seizure duration may become too brief for clinical benefit. Use of higher-energy stimuli may lengthen seizures but may also increase the risk of toxicity, and it is not possible when maximum settings are reached. The authors present the cases of six drug-free depressed inpatients whose seizure durations in ECT declined despite maximum settings on three different ECT devices. In all cases, pretreatment with caffeine lengthened seizures (mean increase = 107%), and clinical improvement followed. Caffeine was well tolerated, even in patients with cardiovascular diseases.
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PMID:Use of caffeine to lengthen seizures in ECT. 363 12

In this study, eight patients participated in a standardized protocol to assess the effects of caffeine on seizures in ECT. Caffeine sodium benzoate (500-2000 mg) was administered intravenously 10 minutes before ECT, and seizure duration was compared with that of a previous treatment unmodified by caffeine. Seizure duration was significantly increased during ECTs preceded by caffeine. Three other patients given caffeine when seizures of adequate duration could no longer be elicited at maximal stimulus levels experienced longer seizures. Administration of caffeine was not associated with significant cardiovascular or other (including cognitive) adverse effects.
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PMID:Facilitation of ECT by caffeine pretreatment. 363 18

The pro-convulsant actions of theophylline and caffeine have been investigated using the hippocampal slice preparation and rats administered kainic acid or Metrazol. Both theophylline and caffeine induced the generation of epileptiform activity in the CA3 region of the hippocampal slice with convulsive dose50 (CD50) values of 3 microM respectively. Kainic acid-induced bursting in hippocampal slices was enhanced by theophylline (0.3-30 microM) and caffeine (1-100 microM). Theophylline induced burst firing in response to electrical stimulation in hippocampal area CA3 but not area CA1. Theophylline (50 mg/kg) strongly potentiated the effect of the limbic convulsant kainic acid in vivo whilst a dose of 200 mg/kg was necessary to significantly lower the threshold dose of Metrazol required to induce generalized convulsions. We conclude that alkylxanthines, probably by antagonizing the effect of endogenous adenosine, exert a pro-convulsant action in the hippocampus which preferentially promotes limbic seizures.
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PMID:Pro-convulsant actions of theophylline and caffeine in the hippocampus: implications for the management of temporal lobe epilepsy. 369 Mar 22

We report two infants with near miss sudden infant death syndrome events exhibiting seizure disorders after caffeine treatment, suggesting there is an infant subgroup diagnosed as near miss sudden infant death syndrome who have apnoea possibly with seizures whose seizure threshold may be lowered by central nervous system stimulants like caffeine.
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PMID:Apnoea and seizures. 374 Sep 28

This study investigates the ability of adenosine antagonists to reverse the anticonvulsant effects of carbamazepine on amygdala-kindled seizures in order to elucidate the possible physiological relevance of the potent effects of carbamazepine on adenosine receptors. At large but subconvulsant doses, neither caffeine nor theophylline altered the anticonvulsant potency of carbamazepine, even though caffeine by itself significantly increased the duration of the kindled afterdischarge. The adenosine agonist cyclohexyladenosine (CHA), administered intraperitoneally at a dose that produced sedation, had no effect on the kindled seizures. Although carbamazepine potently displaces the binding of several adenosine ligands in vitro, the present data do not suggest that the anticonvulsant effects of carbamazepine on amygdalakindled seizures are mediated by an adenosine agonist-like action.
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PMID:Adenosine antagonists. Lack of effect on the inhibition of kindled seizures in rats by carbamazepine. 402 74

Inbred mouse strains SWR and CBA differ markedly in their relatively susceptibility to the acute toxic effects of intraperitoneally administered caffeine. At a dose of 187 mg/kg, SWR mice survive a stress-potentiated lethality test apparently related to the generation of tonic seizures; in contrast, CBA mice usually die in less than 30 seconds after this dose. Progeny from several different genetic crosses were characterized to determine the genetic basis underlying this phenotypic difference in caffeine sensitivity. F1 progeny from reciprocal crosses of the parental strains were uniformly sensitive to caffeine-induced lethality, i.e., caffeine responsiveness behaves like an autosomal dominant trait. Self-crossing of F1 individuals produced both progeny which were resistant to caffeine-induced lethality (26% of the total) and those which were susceptible (74%). Backcrosses of the F1 animals to the CBA parent produced no (0/19) resistant progeny. In contrast, backcrosses of F1 animals to SWR produced 54% resistant progeny. These data indicate that the difference in susceptibility to caffeine-induced lethality between these strains is determined by a single pair of autosomal alleles in which susceptibility (responsiveness) to this methylxanthine is dominant to resistance (nonresponsiveness).
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PMID:A single gene difference determines relative susceptibility to caffeine-induced lethality in SWR and CBA inbred mice. 405 13


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