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

The role of adenosine A1 receptors in the activity of drugs and substances protecting against seizures evoked by mitochondrial toxin, 3-nitropropionic acid (3-NPA) was studied in mice. Non-selective A1/A2 adenosine receptor antagonist, aminophylline and selective A1 adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) diminished the anticonvulsive effects of diazepam, phenobarbital, valproate and gabapentin. In contrast, A1/A2 adenosine receptor antagonist, 8-(p-sulfophenyl)theophylline (8pSPT) not penetrating via blood-brain barrier was ineffective. Aminophylline and DPCPX but not 8pSPT also reversed the protective action of A1/A2 adenosine receptor agonist, 2-chloroadenosine (2-CADO) and selective A1 adenosine receptor agonist, R-N6-phenylisopropyloadenosine (R-PIA), against 3-NPA-evoked convulsions. Obtained results suggest that the central adenosine A1 receptor stimulation may play a role in the anticonvulsive potential of diazepam, phenobarbital, valproate and gabapentin in a novel model of 3-NPA-evoked seizures. Moreover, concomitant application of aminophylline with these drugs may reduce their clinical antiepileptic efficacy, especially among patients suffering from seizures related to the disturbances of mitochondrial respiratory chain.
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PMID:Adenosine A1 receptors and the anticonvulsant potential of drugs effective in the model of 3-nitropropionic acid-induced seizures in mice. 1557 77

Adenosine, as the brain's endogenous anticonvulsant, is considered to be responsible for seizure arrest and postictal refractoriness. On the other hand, deficiencies within the adenosine-based neuromodulatory system may contribute to epileptogenesis. Based on these natural mechanisms and on findings that adenosine and its analogs can suppress pharmacoresistant seizures, a new field of adenosine-based therapies has emerged, including the use of adenosine receptor agonists and adenosine transport inhibitors, or the inhibition of adenosine kinase, which is thought to be the key enzyme for the regulation of intra- and extracellular adenosine levels. However, most of these pharmacological approaches are limited by strong systemic side effects ranging from a decrease of heart rate, blood pressure, and body temperature to sedation. Recently, new strategies have been developed aimed at the local reconstitution of the inhibitory adenosinergic tone by intracerebral implantation of cells engineered to release adenosine. Adenosine-releasing cells or devices implanted into or near a seizure focus offer new hopes for a side effect-free therapy for pharmacoresistant epilepsy.
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PMID:Adenosine and epilepsy: from therapeutic rationale to new therapeutic strategies. 1563 76

Renal damage frequently complicates perinatal asphyxia. Renal vasoconstriction due to adenosine metabolite leads to a fall in glomerular filtration rate (GFR) and filtration fraction. This might be inhibited by the nonspecific adenosine receptor antagonist, theophylline. This study was designed to determine whether theophylline could prevent and/or ameliorate renal dysfunction in term neonates with perinatal asphyxia. We randomized 40 severely asphyxiated term infants to receive intravenously a single dose of either theophylline (5 mg/kg; study group: n=20) or placebo (control group: n=20) during the first hour of life. Fluid intake, urine output, serum creatinine, creatinine clearance, GFR, urinary beta2 microglobulin (beta2 M) and sodium excretion were recorded during the first 5 days of life. The two groups were comparable. No significant difference was reported regarding mechanical ventilatory support, respiratory complications and seizures. Severe renal dysfunction was significantly higher in the control group. Serum creatinine values were less, and creatinine clearance and GFR were significantly higher in the theophylline group from the second day onwards. beta2 M excretion was significantly less in the theophylline group, while sodium excretion and hematuria showed no significant difference. Prophylactic theophylline treatment, given early after birth, has beneficial effects in reducing the renal involvement in asphyxiated full-term infants, with no significant changes in central nervous system involvement.
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PMID:Prophylactic theophylline to prevent renal dysfunction in newborns exposed to perinatal asphyxia--a study in a developing country. 1693 25

In the present study, we investigated the effects of micro-injecting 2-chloroadenosine (2-CADO; an adenosine receptor agonist) into the thalamus alone and with theophylline (a nonspecific adenosine receptor antagonist) pretreatment on pentylenetetrazol (PTZ)-induced tonic-clonic seizures in male Wistar albino rats. Following intrathalamic 2-CADO injection alone or theophylline pretreatment, 50 mg kg(-1) PTZ was given ip after 1 and 24 hrs. The duration of epileptic seizure activity was recorded by cortical electroencephalogram (EEG), and seizure severity was behaviorally scored. Intrathalamic 2-CADO administration induced significant decreases in both seizure duration and seizure severity scores at 1 and 24 hrs, but the effects were more abundant on the seizures induced after 24 hrs. On the other hand, pretreatment with theophylline prevented the inhibitor effect of 2-CADO on seizure activity and increased both seizure duration and seizure scores. Present results suggest that the activation of adenosine receptors in the thalamus may represent another anticonvulsant/modulatory site of adenosine action during the course of the PTZ-induced generalized tonic-clonic seizures and provide additional data for the involvement of the adenosinergic system in the generalized seizures model.
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PMID:Suppression of generalized seizures activity by intrathalamic 2-chloroadenosine application. 1598 26

The involvement of adenosine receptor agonists in benzodiazepine withdrawal signs was evaluated as the seizure susceptibility of mice. The concomitant administration of subthreshold dose of pentetrazole (55.0 or 60.0 mg/kg, s.c.) with flumazenil (10.0 mg/kg, i.p.) in mice chronically treated with temazepam or diazepam induced the appearance of withdrawal signs: clonic seizures, tonic convulsions and death episodes. The administration of the selective A1 (CPA-N6-cyclopentyladenosine), A2A (CGS 21680-2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride) and the non-selective A1/A2A (NECA-5'-N-ethylcarboxamidoadenosine) adenosine receptor agonists (i.p.) evoked the significant attenuation of benzodiazepine withdrawal signs, and these effects were more expressed in temazepam- than in diazepam-dependent mice. CPA has shown the most apparent and dose-dependent attenuating effect. The results confirm that adenosine A1 and A2A receptors are involved in benzodiazepine withdrawal signs, and adenosine A1 receptor plays a predominant role in this phenomenon.
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PMID:Influence of adenosine receptor agonists on benzodiazepine withdrawal signs in mice. 1622 42

EEG and motor phenomena elicited by stimulation of sensorimotor cortex were used to study the effects of chronic postnatal administration of caffeine (10 and 20 mg/kg, s.c. from P7 to P11) in rats. Rhythmic electrical stimulation was applied to 12-, 18-, 25- and 67-day-old rats with implanted electrodes. Animals with the higher dose of caffeine exhibited increased thresholds for elicitation of stimulation-bound movements, spike-and-wave afterdischarges (ADs) and clonic seizures accompanying these ADs at the age of 12 days and decreased duration of spike-and-wave ADs at postnatal days (P) 18 and 25. In contrast, chronic administration of the lower dose of caffeine resulted in a proconvulsant effect expressed as a significant prolongation of spike-and-wave ADs in P12, P18 and P25 groups as well as of the second "limbic" type of ADs (significant only in P12 and P25). The biphasic action of chronic postnatal caffeine treatment was transient and was no longer present in 67-day-old rats. Our results demonstrate that early postnatal caffeine exposure results in either pro- or anticonvulsant effect during brain maturation in relation to the dose used. Caffeine is a mixed adenosine receptor antagonist, therefore its effects could be due to a different action on adenosine receptor subtypes; an additional mechanism of action cannot be excluded.
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PMID:Biphasic effect of chronic postnatal caffeine treatment on cortical epileptic afterdischarges during ontogeny in rats. 1651 71

Depression is a common psychiatric problem in epileptic patients. Thus, it is important that an antidepressant agent has anticonvulsant activity. This study was organized to investigate the effects of tianeptine, an atypical antidepressant, on pentylenetetrazole (PTZ)-induced seizure in mice. A possible contribution of adenosine receptors was also evaluated. Adult male Swiss-Webster mice (25-35 g) were subjects. PTZ (80 mg/kg, i.p.) was injected to mice 30 min after tianeptine (2.5-80 mg/kg, i.p.) or saline administration. The onset times of 'first myoclonic jerk' (FMJ) and 'generalized clonic seizures' (GCS) were recorded. Duration of 600 s was taken as a cutoff time in calculation of the onset time of the seizures. To evaluate the contribution of adenosine receptors in the effect of tianeptine, a nonspecific adenosine receptor antagonist caffeine, a specific A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a specific A2A receptor antagonist 8-(3-chlorostyryl) caffeine (CSC) or their vehicles were administered to the mice 15 min before tianeptine (80 mg/kg) or saline treatments. Tianeptine (40 and 80 mg/kg) pretreatment significantly delayed the onset time of FMJ and GCS. Caffeine (10-60 mg/kg, i.p.) dose-dependently blocked the retarding effect of tianeptine (80 mg/kg) on the onset times of FMJ and GCS. DPCPX (20 mg/kg) but not CSC (1-8 mg/kg) blocked the effect of tianeptine (80 mg/kg) on FMJ. Our results suggest that tianeptine delayed the onset time of PTZ-induced seizures via adenosine A1 receptors in mice. Thus, this drug may be a useful choice for epileptic patients with depression.
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PMID:Effects of tianeptine on onset time of pentylenetetrazole-induced seizures in mice: possible role of adenosine A1 receptors. 1682 86

Adenosine is considered to be the brain's endogenous anticonvulsant as many studies have showed and it is responsible for seizure arrest and postictal refractoriness. Alterations in the adenosinergic system (adenosine and its receptors) have been referred by many previous studies indicating that deficiencies or modifications in the function of this purinergic system may contribute to epileptogenesis. Due to this emerging implication of adenosine in the managing of seizures, a new field of adenosine-based therapies has been introduced including adenosine itself, adenosine receptor agonists and antagonists and adenosine kinase inhibitors. The method with the least side effects (heart rate, blood pressure, temperature or even sedation) is being quested including intracerebral implantation of adenosine releasing cells or devices.
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PMID:Modulatory role of adenosine and its receptors in epilepsy: possible therapeutic approaches. 1684 57

ATP-sensitive K (K(ATP)) channels, widely expressed in cytoplasmic membranes of neurons, couple cell metabolism to excitability. They are considered to play important roles in controlling seizure activity during hypoxia and in neuroprotection against cell damage during hypoxia, ischemia and excitotoxicity. It is known that adenosine augments the opening of cardiac surface K(ATP) channels by reducing the sensitivity of these channels to ATP blockade. We investigated whether a similar modulation occurs in neuronal channels. Whole cell voltage-clamp recordings were made using rat midbrain slices to record the membrane current and conductance in principal neurons of the substantia nigra pars compacta (SNc). When the pipette solution contained 1 mM ATP, the membrane current at -60 mV and cellular conductance remained stable for at least 15 min. When slices were treated with (-)-N(6)-2-phenylisopropyl adenosine (R-PIA), a selective agonist for A(1) adenosine receptors, in the same condition, the outward current developed slowly to the amplitude of 109.9+/-26.6 pA, and conductance increased to 229+/-50% of the baseline. These changes were strongly inhibited by 200 microM tolbutamide, a K(ATP) channel blocker, suggesting that opening of K(ATP) channels mediated these changes. Pretreatment with 8-cyclopentyltheophylline (CPT), a selective A(1) adenosine receptor antagonist, abolished the outward current and conductance increases. Treatment of adenosine resulted in the similar changes sensitive to tolbutamide. These changes were abolished by CPT. These results suggest that activation of A(1) adenosine receptors promotes the opening of K(ATP) channels in principal neurons of the SNc by removing the blockade by ATP.
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PMID:A1 adenosine receptor-mediated modulation of neuronal ATP-sensitive K channels in rat substantia nigra. 1708 18

The aim of the present experiment was to assess the involvement of adenosine receptor antagonists in benzodiazepine (BDZ) withdrawal signs, observed as the seizure susceptibility in mice. The discontinuation of chronic treatment with temazepam or diazepam decreased seizure threshold (one of BDZ withdrawal signs). The concomitant application of subconvulsive dose of pentetrazole (55.0 mg/kg) with low dose of flumazenil (5.0 mg/kg) - a BDZ receptor antagonist, immediately induced BDZ withdrawal signs in these animals. The non-selective adenosine receptor antagonist (caffeine), and the selective adenosine A1 receptor antagonist (DPCPX), injected 15 min before the application of pentetrazole and flumazenil, were able to intensify BDZ withdrawal signs in mice. The most apparent effects were observed after administration of DPCPX, indicating that the adenosine A1 receptor may play a more important role in these effects. The obtained data demonstrate that the adenosinergic system is involved in BDZ withdrawal signs in mice, and adenosine A1 receptor plays an important role in this process.
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PMID:Adenosine receptor antagonists intensify the benzodiazepine withdrawal signs in mice. 1708 56


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