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

Studies have shown that adenosine analogs may modulate kindled seizures. The present study demonstrated that systemic administration of the adenosine analog, L-phenylisopropyladenosine (L-PIA), substantially prolonged the postictal depression and decreased the frequency of spiking that follows amygdala-kindled seizures in rats. Fully kindled rats were administered L-PIA (0.1 to 2.0 mg/kg, i.p.) or saline 30 min before stimulation of the amygdala. Afterdischarge durations with L-PIA did not differ from those with saline, and behavioral seizures were only slightly decreased in severity with 2.0 mg/kg L-PIA. However, 0.5 to 2.0 mg/kg L-PIA increased the duration of the postictal depression by more than 20 min and, at 2.0 mg/kg, L-PIA decreased the frequency of postictal spiking. Postictal administration of caffeine (32 mg/kg, i.p.) reversed the prolongation of the postictal depression induced by 1.0 mg/kg L-PIA. These effects did not seem to be mediated by peripheral actions of L-PIA (i.e., lowered blood pressure) as hydralazine, which decreases blood pressure through peripheral mechanisms, did not affect ictal or postictal events. These results indicate that adenosine may modulate neuronal excitability that follows kindled seizures.
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PMID:Prolonged postictal depression in amygdala-kindled rats by the adenosine analog, L-phenylisopropyladenosine. 406 71

Mice of the DBA/2/M strain are audio-sensitive only for a short period (5 to 10 days). When this period is over, 100 p. 100 audiogenic seizures can be obtained with experimental magnesium deficiency. When AKR/R, OF1 and C57BL/R mice were deprived of magnesium for 15 or 21 days, they manifested an audiogenic attack only when given amphetamine sulfate, caffeine or isonicotinylhydrazine. If they had been deprived for 43 days, it was no longer necessary to administer these substances. The audiogenic attack could be prevented by correcting the deficiency with magnesium chloride or by preliminary administration of a single dose of various barbiturics, anti-convulsives, tranquillizers or parachlorophenylalanine, but not neuroleptics.
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PMID:[Audiogenic seizure in the mouse according to strain and sex: the effect of the magnesium ration and neuromediators]. 613 May 80

Abuse of amphetamine and especially the stimulant look-alikes represent a serious problem in the United States. The danger of amphetamine lies in its ability to produce tolerance, psychological addiction, psychosis, hypertensive crisis, and major depression following withdrawal after long-term use. The danger of the look-alikes is of a psychosocial nature and has less to do with the physical properties of the drugs. Easy availability and a casual attitude toward these drugs may introduce children and young adults to the concept of recreational use of drugs at an early age. Look-alikes also divert the efforts of law enforcement officials whose time is better spent on efforts to control illegal distribution of controlled substances. However, look-alikes do produce severe to life-threatening effects including seizures, hypertensive crises, and psychoses. Unfortunately, there are no fast and easy solutions to the stimulant drug abuse problem. Abuse of CNS stimulants has a long history. Effective approaches must involve greater education about the dangers of these drugs and improved recognition among medical professionals of trends in CNS stimulant abuse in order to better diagnose and treat resulting problems. It is unlikely that federal controls on amphetamine production can be increased. The OTC drugs, such as PPA, caffeine, and ephedrine could be moved to prescription-only status to emphasize their potential for abuse and for producing adverse reactions, but this approach is counter to society's current trend toward self-medication.
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PMID:CNS stimulants and the look-alike drugs. 615 45

Several purines have been shown to be competitive inhibitors of [3H] diazepam binding. Inosine has also been shown to have benzodiazepine-like neurophysiologic, pharmacologic and behavioral effects, and to partially inhibit caffeine-induced seizures in mice. Using presumptive therapeutic doses of inosine, levels were determined in mouse brain at various times following injection. Inosine and hypoxanthine concentrations in brain increased several fold following inosine administration, indicating that inosine permeated the blood-brain barrier. The levels of inosine and hypoxanthine attained in brain were sufficient to inhibit by more than 50% the GABA-stimulated [3H] diazepam binding. These data suggest that the anticonvulsant properties of inosine are related to its interaction with the benzodiazepine receptor.
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PMID:Anticonvulsant doses of inosine result in brain levels sufficient to inhibit [3H] diazepam binding. 627 42

A patient who allegedly consumed 100 tablets of an over-the-counter analgesic containing sodium acetylsalicylate, caffeine, and acetaminophen displayed no significant CNS stimulation despite the presence of 175 micrograms of caffeine per mL of serum. Because salicylates have been reported to augment the stimulatory effects of caffeine on the CNS, attention was focused on the possibility that the presence of acetaminophen (52 micrograms/mL) reduced the CNS toxicity of caffeine. Studies in DBA/2J mice showed that: 1) pretreatment with acetaminophen (100 mg/kg) increased the interval between the administration of caffeine (300 to 450 mg/kg IP) and the onset of fatal convulsions by a factor of about two; and 2) pretreatment with acetaminophen (75 mg/kg) reduced the incidence of audiogenic seizures produced in the presence of caffeine (12.5 to 75 mg/kg IP). The frequency of sound-induced seizures after 12.5 or 25 mg/kg caffeine was reduced from 50 to 5% by acetaminophen. In the absence of caffeine, acetaminophen (up to 300 mg/kg) did not modify the seizures induced by maximal electroshock and did not alter the convulsant dose of pentylenetetrezol in mice (tests performed by the Anticonvulsant Screening Project of NINCDS). Acetaminophen (up to 150 micrograms/mL) did not retard the incorporation of radioactive adenosine into ATP in slices of rat cerebral cortex. Thus the mechanism by which acetaminophen antagonizes the actions of caffeine in the CNS remains unknown.
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PMID:Reduction in caffeine toxicity by acetaminophen. 630 77

Hypertension, severe headache, and grand mal seizures developed in a 13-year-old girl after ingestion of one nonprescription diet pill containing phenylpropanolamine and caffeine. This case is at least the sixth report of seizures with phenylpropanolamine use in children or adolescents. Phenylpropanolamine ingestion must be included in the differential diagnosis of young patients, particularly adolescents, in whom acute neurological symptoms develop.
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PMID:Phenylpropanolamine-associated CNS complications in children and adolescents. 642 18

Over-the-counter stimulants (phenylpropanolamine hydrochloride, ephedrine, pseudoephedrine, caffeine) are used widely as decongestants, anorectic agents, amphetamine substitutes, and "legal stimulants." Toxic effects may result from overdose, drug interactions, or diseases that increase sensitivity to sympathomimetic agents. The most important toxic effect of the alpha-adrenergic agonist phenylpropanolamine is hypertension, which may result in hypertensive encephalopathy or intracerebral hemorrhage. The therapeutic index of phenylpropanolamine is low, and severe hypertension may occur after ingestion of less than three times the therapeutic dose. Ephedrine and pseudoephedrine may also cause hypertension, as well as tachyarrhythmias due to beta-adrenergic stimulation. Toxic reactions from caffeine are characterized by agitation, seizures, tachyarrhythmias, and hypotension. Management of toxic reactions to over-the-counter stimulants includes control of hypertension with a rapidly acting vasodilator, beta-blockers for tachyarrhythmias, and control of seizures.
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PMID:Toxicity of over-the-counter stimulants. 647 21

Rats were kindled during exposure to caffeine (50 mg/kg) or saline given IP twenty minutes before daily electrical stimulation of the amygdala until 3 kindled amygdaloid seizures (KAS) occurred. They were then stimulated for 3 days without drug pretreatment followed by 5 additional days with drug pretreatment. There were no significant differences between the two groups in the number of daily stimulations or in the total seconds of cumulative afterdischarge (AD) needed to reach the first KAS. During kindling, the daily average AD tended to be longer in the caffeine treated group. This difference became significant (greater than 200% saline) when the KAS was reached. When KAS animals were stimulated without caffeine pretreatment, the average AD returned to control lengths. When put back on caffeine pretreatment, the average AD was again increased. Caffeine (6-50 mg/kg, IP) was also evaluated in previously kindled rats using suprathreshold (400 mu AMP) and threshold (20 microA increments) seizures. Caffeine had no consistent effect on threshold values. However, 12-50 mg/kg of caffeine increased seizure severity and AD durations after threshold stimulation. With suprathreshold stimulation, the length of the AD was significantly increased only after the highest dose of caffeine. It would appear that caffeine lengthens induced afterdischarges both during the acquisition phase of kindling and in the fully kindled subject. Caffeine does not appear to lower seizure thresholds or increase the rate of acquisition of the KAS in the doses tested in this model.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Caffeine modification of kindled amygdaloid seizures. 663 84

To test the hypothesis that kindling is restrained by the inhibitory neuromodulator, adenosine, the adenosine uptake blocker, papaverine, or the adenosine antagonist, aminophylline, were injected systemically into rats 20 min before each daily electrical stimulation of the amygdala. The effects on amygdala-triggered seizures of papaverine, adenosine, 2-chloroadenosine, and the adenosine antagonists, isobutylmethylxanthine and caffeine, were also investigated at seizure threshold. Papaverine inhibited kindling, whereas aminophylline accelerated kindling. The adenosine agonists had anticonvulsant effects on seizures, and the antagonists had proconvulsant effects which involved, primarily, the lengthening of afterdischarge duration. Aminophylline injected repeatedly, in the absence of electrical stimulation, induced seizures. These results support the hypothesis that adenosine can modulate kindling and affect the seizure process.
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PMID:Adenosine modulation of amygdala kindling. 672 86

Acute toxic dosage-dependent behavioral effects of caffeine were compared in adult males from seven inbred mouse strains (A/J, BALB/cJ, CBA/J, C3H/HeJ, C57BL/6J, DBA/2J, SWR/J). C57BL/6J, chosen as a "prototypic" mouse strain, was used to determine behavioral responses to a broad range (5-500 mg/kg) of caffeine doses. Five phenotypic characteristics--locomotor activity, righting ability, clonic seizure induction, stress-induced lethality, death without external stress--were scored at various caffeine doses in drug-naive animals under empirically optimized, rigidly constant experimental conditions. Mice (n = 12 for each point) received single IP injections of a fixed volume/g body weight of physiological saline carrier with or without caffeine in doses ranging from 125-500 mg/kg. Loss of righting ability was scored at 1, 3, 5 min post dosing and at 5 min intervals thereafter for 20 min. In the same animals the occurrence of clonic seizures was scored as to time of onset and severity for 20 min after drug administration. When these proceeded to tonic seizures, death occurred in less than 20 min. Animals surviving for 20 min were immediately stressed by a swim test in 25 degrees C water, and death-producing tonic seizures were scored for 2 min. In other animals locomotor activity was measured 15 or 60 min after caffeine administration. By any single behavioral criterion or a combination of these criteria, marked differences in response to toxic caffeine doses were observed between strains. These results indicate that behavioral toxicity testing of alkylxanthines in a single mouse strain may be misleading and suggest that toxic responses of the central nervous system to this class of compounds are genetically influenced in mammals.
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PMID:Interstrain variation in acute toxic response to caffeine among inbred mice. 672 73


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