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

The incidence and proposed mechanisms of apnea of infancy and apnea of prematurity are briefly reviewed, and the use of methylxanthines in managing these conditions is discussed. Apnea may result from incomplete neurological development of the infant. A sleep-related defect in respiratory control mechanisms has been proposed. Apnea may be secondary to physiologic abnormalities that cause airway obstruction or to cardiac disease or arrhythmia, seizure disorders, infection, or other disorders. Therapy often includes supportive management. The primary pharmacologic agents used to treat apnea of prematurity are caffeine and theophylline. The metabolism of these drugs differs greatly between newborns and adults and changes rapidly in the first nine months of life; in infants up to 4 1/2 months of age, the half-life of these compounds is prolonged. While only theophylline is approved in the United States for management of apnea, caffeine has several potential advantages. However, no suitable caffeine product is available. The accepted pharmacologic treatment for apnea of prematurity is the use of the methylxanthines theophylline and caffeine. Theophylline has also been used in treating apnea of infancy, although there are fewer data documenting its efficacy for this indication.
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PMID:Management of apnea in infants. 267 Mar 99

The convulsant properties of xanthine amine congener (XAC, 8-(4-(2-aminoethyl)-aminocarboxylmethyloxy)phenyl-1,3-dipropylxant hine) are compared to those of caffeine. Male Swiss albino mice were infused with convulsants through a lateral tail vein. Convulsion thresholds (i.e. the amount of convulsants required to elicit convulsions) of 39.8 +/- 2.0 mg/kg (n = 10) and 109.8 +/- 2.3 mg/kg (n = 10) were calculated for XAC and caffeine respectively. Pretreatment of animals with the adenosine receptor agonists 2-chloroadenosine, N6-cyclohexyladenosine or 5'-N-ethylcarboxamido-adenosine (1 mg/kg, i.p., 20 minutes prior to infusion) significantly decreased the seizure threshold of both XAC and caffeine. The adenosine uptake blockers, 6-nitrobenzylthioinosine or dipyridamole (0.25 mg/kg, i.p., 20 minutes prior to infusion) did not significantly affect the seizure threshold to either XAC or caffeine. The benzodiazepine agonist diazepam (5 mg/kg, i.p., 20 minutes prior to infusion) significantly increased the seizure threshold to both XAC (p less than 0.05) and caffeine (p less than 0.01), whereas the benzodiazepine antagonist Ro 15-1788 (10 mg/kg, i.p., 20 minutes prior to infusion) significantly increased the seizure threshold to caffeine (p less than 0.01), but not XAC. The results suggest that actions at benzodiazepine receptors may be a tenable hypothesis to explain the convulsant actions of caffeine, but not those of XAC.
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PMID:Potent convulsant actions of the adenosine receptor antagonist, xanthine amine congener (XAC). 277 59

Two strains of inbred mice differed significantly in their susceptibility to tonic seizures induced by caffeine and the benzodiazepine inverse agonist, methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM). The hyporesponsive strain, SWR, was not less susceptible to the convulsant action of other chemical convulsants, an observation which indicated that the response differences between the strains were pharmacologically specific. These observations and drug interaction studies suggested that caffeine-induced seizures might be mediated through an "inverse" agonist-like action of caffeine on benzodiazepine receptors associated with GABA receptor-benzodiazepine receptor-chloride ionophore complex. To determine whether the coincident alteration in susceptibility to DMCM and caffeine resulted from a single mutational change or was the result of two different genetic changes occurring coincidentally between these two strains of mice, progeny from conventional Mendelian crosses (F1, F2 and reciprocal backcrosses) were analyzed for the co-segregation of susceptibility to DMCM and caffeine. The inheritance of DMCM sensitivity was consistent with a single autosomal gene determinant in which the allele specifying increased responsiveness was dominant to the allele determining hyporesponsiveness. The frequent occurrence of recombinant phenotypes (e.g., caffeine hyporesponsive but DMCM sensitive mice) among F2 and backcross progeny established that different genetic determinants encode DMCM susceptibility and caffeine susceptibility in these two strains of mice. Thus, while these data establish a simply inherited difference in benzodiazepine responsiveness between the two mouse strains, they also indicate that this pair of strains is inappropriate for a genetic analysis aimed at probing the relationship between caffeine-induced seizures and the benzodiazepine receptor.
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PMID:Different genes specify hyporesponsiveness to seizures induced by caffeine and the benzodiazepine inverse agonist, DMCM. 282 52

The effects of various doses of caffeine and of chlor-desmethyldiazepam on footshock-induced aggressive behavior were examined in mice with different baselines of aggressiveness. Caffeine significantly increased the number of fighting episodes with all the doses tested. This was more evident in mice with low rather than in those with high basal rates of agonistic response. Caffeine caused the appearance of minimal convulsive signs in mice subjected to a threshold electroshock which did not produce any seizure in the controls; it also increased metrazol toxicity. Chlor-desmethyldiazepam enhanced fighting behavior at doses of 0.04 and 0.08 mg/kg, but decreased it at 1.25 mg/kg. The first two doses produced the same effects as caffeine on electroshock test, but did not influence metrazol toxicity.
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PMID:Effects of caffeine and chlor-desmethyldiazepam on fighting behavior of mice with different reactivity baselines. 286 50

The median inhibitory and anticonvulsant potencies of seven benzodiazepine (BDZ) agonists and one BDZ antagonist (Ro15-1788) were established by two tests: inhibition of [3H]flunitrazepam receptor binding and prevention of caffeine-induced seizures in mice. The effect of Ro15-1788 on the anticonvulsant potency of diazepam against caffeine-induced seizures was also investigated. The [3H]flunitrazepam receptor binding inhibitory potencies (IC50s) of the BDZ agonists correlate well with their anticonvulsant potencies (ED50s) against caffeine-induced seizures (r = 0.831; P greater than 0.01 and less than 0.05). Ro15-1788 and clonazepam are the most potent inhibitors (IC50s: 1.72 and 1.75 nM, respectively), but differ markedly in their ability to obtund caffeine-induced seizures (ED50s: 43.2 and 0.226 mg/kg, respectively). Although both Ro15-1788 and diazepam are effective against caffeine-induced seizures, when used in combination Ro15-1788 antagonizes the anti-caffeine effect of diazepam. These data indicate that Ro15-1788 is a BDZ partial agonist with low efficacy as well as a potent antagonist.
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PMID:Benzodiazepine inhibition of [3H]flunitrazepam binding and caffeine-induced seizures in mice. 287 63

It is well established that at low and clinically relevant concentrations theophylline (and caffeine) exerts antagonism at cell surface receptor sites for adenosine. However, it is not known which actions of theophylline are due to adenosine antagonism, because theophylline apparently activates other cellular mechanisms at the same low concentrations. Investigations into the actions of xanthines and their structure activity relationships have identified xanthine compounds like enprofylline (3-propylxanthine) that only has some actions in common with theophylline and that has a negligible ability to antagonize adenosine. Enprofylline is a more potent smooth muscle relaxant and antiasthmatic drug than theophylline but does not produce, e.g., theophylline-like diuretic effects, CNS-stimulant behavioural effects (restlessness - seizures), gastric secretory effects and release of free fatty acids. It is proposed that pharmacodynamic dissimilarities between enprofylline and theophylline may indicate physiological roles of adenosine.
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PMID:Effects of enprofylline and theophylline may show the role of adenosine. 300 2

The neurological tottering mutant mouse is characterized by frequent "absence" seizures accompanied by bilateral synchronous spike and wave EEG bursts. Under anesthesia, adult homozygous tottering mice were implanted with permanent epidural electrodes, and at least 7 days elapsed before electrocorticograms in unrestrained mice were scored for seizure incidence and duration. Caffeine (5, 10, 15 mg/kg, n = 8) injected intraperitoneally (i.p.) at the fourth hour of 8-h recording sessions significantly (p less than 0.001 for 10 and 15 mg) decreased seizure incidence as compared with control saline injections. Spike and wave bursts were eliminated during the 30 min after injection and reached 50% preinjection levels between the first and the second hour after injection. Another central nervous system (CNS) stimulating drug, amphetamine (1 mg/kg; n = 5), under identical conditions failed to decrease seizure incidence in this mutant.
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PMID:Caffeine blocks absence seizures in the tottering mutant mouse. 311 28

Theophylline can cause life-threatening seizures when administered in excessive doses. The plasma concentrations associated with this neurotoxic effect vary widely among patients. To determine the reasons for the wide variation, an animal model of theophylline-induced seizures was developed and has now been used to determine the effect of pre-exposure to caffeine on theophylline-induced neurotoxicity. Male adult rats received an iv infusion of either caffeine citrate or sodium citrate solution for 15 min. Theophylline was then infused at a relatively rapid rate until onset of maximum seizures. A third group of rats received a rapid infusion of caffeine only until onset of seizures. Samples of blood, brain, and cerebrospinal fluid were obtained at that time for determination of caffeine and theophylline concentrations by HPLC. Prior exposure to caffeine was associated with a statistically significant reduction in the total amount of theophylline required to produce seizures and caused theophylline concentrations at all sampling sites to be significantly lower than in controls. Caffeine alone required a larger total dose and higher concentrations than theophylline alone to produce seizures. It is concluded that acute exposure to caffeine can increase the risk of theophylline-induced neurotoxicity.
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PMID:Caffeine as a potential risk factor for theophylline neurotoxicity. 322 66

The concentration and time dependence of caffeine-induced neurotoxicity was determined by infusing rats intravenously with caffeine at a rate of about 5, 12.5, and 25 mg kg-1 min-1 until the onset of generalized seizures which occurred at about 82, 28, and 11 min, respectively. The concentration of caffeine in the serum, brain, and cerebrospinal fluid at onset of seizures increased with decreasing infusion rate; the concentrations of caffeine metabolites were negligible and serum protein binding was not affected by the infusion rate. In another experiment, one group of rats was infused with caffeine for 60 min at about 2.2 mg kg-1 min-1 whereas another group was infused with solvent only. Both groups were then immediately infused with caffeine at about 22 mg kg-1 min-1 until onset of seizures. Caffeine concentrations at that time in serum, brain, and cerebrospinal fluid were significantly higher in the caffeine-pretreated animals than in the solvent-pretreated controls. The same pretreatment 17 hr before the fast infusion of caffeine had no apparent effect on caffeine concentrations at onset of seizures. These results show that functional tolerance to the seizure-inducing effect of caffeine in rats develops within minutes and that it is reversible within hours or less.
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PMID:Rapid development of functional tolerance to caffeine-induced seizures in rats. 325 98

1. The proconvulsant effects of the imidazodiazepine Ro 15-4513, were investigated in mice by use of intravenous infusion of a variety of convulsant drugs. 2. Dose-response and time course studies of Ro 15-4513 against gamma-aminobutyric acid (GABA) antagonists were performed. On the basis of these studies a maximally effective dose of 5 mg kg-1 was administered 5 min before the determination of seizure thresholds in subsequent experiments. 3. Ro 15-4513 (5 mg kg-1) significantly lowered seizure thresholds to pentylenetetrazole, bicuculline and the convulsant benzodiazepine Ro 5-3663, but failed to alter seizure thresholds to picrotoxin, strychnine, caffeine and quipazine. 4. Ro 15-4513 significantly raised seizure threshold to the benzodiazepine receptor inverse agonist methyl 6,7-dimethoxy-4 ethyl-beta-carboline-3-carboxylate (DMCM). 5. These results are discussed in relation to other studies investigating the proconvulsant and alcohol-antagonizing effects of Ro 15-4513.
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PMID:Interactions of the imidazodiazepine Ro 15-4513 with chemical convulsants. 334 29


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