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 evaluated the protective activity (expressed as ED50 values in mg/kg of phenobarbital (PB, 120 min before testing) and valproate (30 min) alone or combined with caffeine in male mice with seizures induced by maximal electroshock (MES). Both antiepileptic drugs (AEDs) were administered by intraperitoneal (i.p.) injection in a single dose to mice receiving intraperitoneal caffeine either in a single dose 30 min before the test or as pretreatment every 12 h for 3 and 14 days. In addition, we determined the ED50 values of the AEDs 24 and 72 h after 14-day treatment with caffeine. Finally, we studied the influence of a challenge dose of caffeine, injected in mice 24 and 72 h after 14 days of treatment with caffeine, on the protective activity of PB or VPA. Caffeine in a single dose of 23.1 mg/kg reduced the anticonvulsant effect of PB. Its protective activity was further impaired after 3 and 14 days of caffeine treatment. The ED50 for VPA was significantly increased both by the single dose of caffeine and by chronic treatment. The anticonvulsant activity of PB and VPA measured 24 and 72 h after 14-day treatment with caffeine did not differ from control values, but a challenge dose of caffeine injected 24 or 72 h after daily injections for 14 days resulted in a significant reduction in the protective activity of both AEDs. Measurement of the total plasma levels of caffeine, VPA, and PB did not suggest pharmacokinetic interactions as an explanation for our results. Our results indicate that chronic caffeine exposure may progressively reduce the antiepileptic potency of VPA and PB.
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PMID:Anticonvulsant activity of phenobarbital and valproate against maximal electroshock in mice during chronic treatment with caffeine and caffeine discontinuation. 859 85

Narcolepsy is a rare sequela of brain injury. We report the case of a 27-yr-old male with post-traumatic narcolepsy who was successfully treated with methylphenidate. This patient sustained moderate brain injury from a motorcycle accident. Subsequently, he manifested the classic tetrad of narcolepsy: cataplexy, excessive daytime sleepiness, sleep paralysis, and hypnogogic hallucinations. There was no premorbid seizure or sleep disorder. There was no family history of sleep disorders. Polysomnography and Multiple Sleep Latency Test confirmed the diagnosis of narcolepsy. Sleep latency (time to sleep onset), rapid eye movement sleep latency (time from sleep onset to rapid eye movement sleep onset), and mean multiple sleep latency were all pathologically shortened (2.5, 66, and 1.2 min, respectively). Twenty-four hour electroencephalographic monitoring and magnetic resonance imaging of the brain were normal, as were serum chemistries. Treatment with caffeine was unsuccessful. He was then started on methylphenidate, 10 mg twice daily, which was increased to 30 mg twice daily over a 4-mo period. Cataplexy and excessive daytime sleepiness started to improve 1 mo after adjustments in methylphenidate dosing. Six months after the initiation of methylphenidate therapy, the patient is completely asymptomatic.
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PMID:Successful treatment of post-traumatic narcolepsy with methylphenidate: a case report. 864 41

A reliable method was sought for the fast screening and simultaneous determination of amphetamine, morphine, heroin (acetomorphine), codeine (methylmorphine) and caffeine in biological fluids and drug seizures. Capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MEKC), with detection at 200 and 220 nm, were investigated for analytes in human serum and urine. When adequate separation was not achieved in preliminary studies with CZE, further development was focused on the MEKC method. Glycine buffer containing sodium lauryl sulfate (pH 10.5) was used for the MEKC separations. The analytes and carboxylic acids used as marker compounds could be screened by a short-capillary method in less than 2 min. In the simultaneous determination of the drugs in urine and serum a longer separation of 18 min was preferred so that all the compounds, the markers and the endogenous compounds absorbing at the detection wavelength could be adequately separated in a single run. The migration times of the compounds increased in the order caffeine, morphine, heroin, codeine and amphetamine. The repeatability of the separation was tested by using two carboxylic acids as marker compounds in the determination of the migration indices of the analytes. The relative standard deviations for the migration indices were less than 1%, which is accurate enough for the determination of the drugs in biological fluids.
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PMID:Determination of morphine analogues, caffeine and amphetamine in biological fluids by capillary electrophoresis with the marker technique. 876 52

We determined postictal refractoriness in Sprague-Dawley rats by comparing lengths of two suprathreshold ECS seizures given 15 s to 24 h apart. A bimodal (immediate and delayed) decrease in seizure duration was found, suggesting ECS alters mechanisms of seizure termination. Since adenosine is implicated in seizure termination, we determined immediate (30 s) and delayed (24 h) postictal ECS refractoriness in Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats which vary in adenosine properties and initial ECS seizure length. At 30 s, the decrease in seizures did not differ between WKY (-44%) and SHR (-36%) rats. At 24 h, SHR rats showed no change while the WKY rats showed a 20% decrease in seizure length (P < 0.01). These two strains also differed in the ability of the adenosine antagonist caffeine (50 mg/kg, i.p.) to prolong ECS seizures (no change for WKY, +13% for SHR, P < 0.001). The results suggest immediate and delayed postictal refractoriness are subject to genetic variation and may depend on central adenosine mechanisms.
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PMID:Genetic variation in immediate and delayed postictal refractory period in rats. 879 95

The anticonvulsant activities of intraperitoneally (IP) given carbamazepine (CBZ) or diphenylhydantoin (DPH), expressed as their respective ED50 values in mg/kg, were assessed after caffeine (CAFF) treatment against maximal electroshock-induced seizures in mice. CAFF was administered IP either in a single dose or every 12 h for 3 (subchronic CAFF) and 14 days (chronic CAFF). Moreover, the protective activity of the antiepileptics was determined in mice which, following chronic CAFF, received a challenge dose of CAFF after either 24 or 72 h since CAFF withdrawal. A significant reduction of the protective efficacy of CBZ was observed after chronic CAFF treatment (in a dose of 11.55 mg/kg), while a single dose and a 3-day treatment did not alter the action of CBZ. In case of CAFF (23.1 mg/kg), a significant elevation of CBZ's ED50 value was noted after 3- and 14-day treatments with CAFF. In contrast, chronic CAFF (23.1-46.2 mg/kg) decreased the anticonvulsive activity of DPH to the same extent as did acute CAFF. Moreover the ED50 values for both, CBZ and DPH, evaluated 24 h after a 14-day treatment with CAFF (in doses of 23.1 and 46.2 mg/kg, respectively), were significantly elevated compared to respective control groups. A strong impairment of the anticon-vulsant action of CBZ and DPH was observed when a challenge dose of CAFF was injected following either 24 or 72 h injection-free time. Pharmacokinetic interactions do not seem to explain the obtained results in terms of total plasma levels of the antiepileptics after chronic treatment with CAFF. Our results may suggest that epileptic patients should avoid CAFF-containing beverages and medicines.
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PMID:Chronic caffeine and the anticonvulsant potency of antiepileptic drugs against maximal electroshock. 885 83

Caffeine-augmented electroconvulsive therapy has been introduced into medical practice without experimental confirmation that such seizure modification does not result in neuronal injury. In this report rats pretreated with caffeine prior to a series of nine electrically induced convulsions showed neuronal injury confined to hippocampal sectors and striatum. Electrically induced convulsions without caffeine pretreatment did not result in injury. The potential deleterious effects of caffeine augmentation of human electroconvulsive therapy require rigorous clinical assessment.
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PMID:Hippocampal neurons are damaged by caffeine-augmented electroshock seizures. 911 Jan 7

Adenosine receptors have been the target of intense research with respect to potential use of selective ligands in a variety of therapeutic areas. Caffeine and theophylline are adenosine receptor antagonists, and over the past three decades a wide range of selective agonists and antagonists for adenosine receptor subtypes have been developed. A complication to the therapeutic use of adenosine receptor ligands is the observation that the effects of acute administration of a particular ligand can be diametrically opposite to the chronic effects of the same ligand. This 'effect inversion' is discussed here by Ken Jacobson and colleagues, and has been observed for effects on cognitive processes, seizures and ischaemic damage.
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PMID:Adenosine receptor ligands: differences with acute versus chronic treatment. 893 47

The effects of long-term oral administration of low doses of caffeine (0.3 g/l) and its metabolites theophylline, theobromine and paraxanthine (each at 0.5 g/l in drinking water) on bicuculline- and pentylenetetrazol (PTZ)-induced seizures and c-fos expression were studied in mice. In addition, adenosine and benzodiazepine receptor density was examined. The plasma levels of the methylxanthines were much higher during the active period at night than during the day. The maximal level of caffeine was 14 microM. Brain theophylline levels (8-13 nmol/g) tended to be higher and more constant than brain caffeine levels in caffeine-consuming mice. Clonic seizures induced by bicuculline (4 mg/kg i.p.) were significantly reduced in severity by 14 day caffeine treatment and mortality was also reduced. Long-term treatment with caffeine metabolites was less effective. The seizures induced by PTZ (60 mg/kg i.p.) were also significantly reduced by long-term caffeine treatment. After bicuculline or PTZ treatment, c-fos mRNA expression was weaker in the cerebral cortex in animals receiving caffeine, irrespective of whether the animals had seizures or not. No significant changes in the binding of adenosine receptor ligands or benzodiazepines were seen after long-term caffeine treatment. These results show that long-term treatment with caffeine in a dose that is commonly seen in humans decreases the seizures induced by bicuculline, and to a lesser extent, those induced by PTZ. This may be related to a decreased neuronal excitability. The effect is due to the combined effects of theophylline, to which caffeine is metabolized in brain, and caffeine itself, but could not be ascribed to changes in A1 and A2A adenosine or benzodiazepine receptors.
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PMID:Long-term treatment with some methylxanthines decreases the susceptibility to bicuculline- and pentylenetetrazol-induced seizures in mice. Relationship to c-fos expression and receptor binding. 899 94

We studied the evolution of the purity and other characteristics of heroin seized in 17 Spanish provinces (especially seizures presumed to be street drugs) and explored their relation with the prevalence and recent changes in intravenous use. We found great variability in purity within and between provinces: in provinces with large cities the purity is similar to or greater than that detected elsewhere in Europe, in others it is less than 30 percent, and on the island of Mallorca it is over 60 percent. Purity has increased in recent years. The heroin in circulation is predominantly brown in all of Spain except on the Mediterranean coast. The principal adulterants detected are caffeine, paracetamol and piracetam; phenobarbital and procaine have disappeared. In provinces where white heroin is in circulation, most heroin users in treatment use the intravenous route; in provinces where brown heroin predominates, the proportion of chasers increases with increasing purity of heroin (correlation coefficient = 0.6). The disappearance of white heroin has paralleled the spread of the phenomenon of chasing.
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PMID:Temporal and geographic variations in the characteristics of heroin seized in Spain and their relation with the route of administration. Spanish Group for the Study of the Purity of Seized Drugs. 906 25

Effects of intraperitoneal and intrahippocampal 2-chloroadenosine and caffeine were examined in fully kindled amygdaloid rats. Intraperitoneal administration of 2-chloroadenosine (5 and 10 mg/kg) decreased afterdischarge duration, stage 5 seizure duration and prolonged time taken to reach stage 4 seizure. Only the 10 mg/kg dose induced a significant reduction in seizure stage. Intraperitoneal administration of caffeine (50 mg/kg) increased both afterdischarge duration and stage 5 seizure duration but did not significantly alter other parameters. Intrahippocampal microinfusion of 2-chloroadenosine (1 mM) or caffeine (2 mM) did not alter any of the measured seizure parameters. Intraperitoneal but not intrahippocampal pretreatment of animals with caffeine (50 mg/kg and 2 mM, respectively) blocked the anticonvulsant effects induced by intraperitoneal administration of 2-chloroadenosine. It may therefore be concluded that the adenosine A1 receptors of the CA1 region of the hippocampus do not play a role in mediating the anticonvulsant effects of intraperitoneally administered 2-chloroadenosine in amygdaloid kindled rats.
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PMID:Effect of intraperitoneal and intrahippocampal (CA1) 2-chloroadenosine in amygdaloid kindled rats. 909 13


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