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

Male Long-Evans rats were stereotaxically implanted with a bipolar electrode in the central amygdala and with a stainless-steel cannula in the lateral cerebral ventricle. Rats were then kindled once daily until 3 consecutive Stage 5 kindled seizures were elicited. Adenosine analogues were injected into the lateral cerebral ventricle to examine their effects on behavioral seizures and afterdischarge duration following a kindling stimulus. 5'-N-ethylcarboxamidoadenosine (NECA) and (-)-N-(1-methyl-2-phenylethyl)-adenosine(L-phenylisopropyladenosine) (L-PIA) produced dose-related reductions of amygdaloid-kindled seizures with NECA exhibiting slightly more potent anticonvulsant activity than L-PIA. Parenteral injections of caffeine, at a dose which had no effect on seizure parameters, antagonized the anticonvulsant effects of NECA. These results are consistent with the notion that adenosine is a modulator of synaptic activity in the CNS and methylxanthines exert a specific antagonism of central adenosine receptors.
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PMID:Anticonvulsant effects of adenosine analogues on amygdaloid-kindled seizures in rats. 673 23

The induction of generalized tonic-clinic seizures in mice by the methylxanthine stimulant caffeine is described. These seizures are indistinguishable in quality from those induced by pentylenetetrazol (PTZ), and pretreatment with low doses of caffeine potentiates PTZ-induced seizures. Benzodiazepines inhibit caffeine-induced seizures with a rank order potency that parallels their affinities for the central nervous system (CNS) benzodiazepine receptor in vitro. Inosine, a purine that has recently been shown to be a competitive inhibitor of [3H] diazepam binding in vitro, antagonizes caffeine-induced seizures, while 7-methyl-inosine, a purine that lacks receptor binding inhibitory activity, has no effect on seizures. Since the benzodiazepines, inosine, caffeine, and pentylenetetrazol all competitively inhibit [3H] diazepam binding and have marked effects on inducing or antagonizing seizures, further study of this receptor-ligand system may provide additional insights that concern possible biochemical mechanisms of seizures.
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PMID:The benzodiazepines and inosine antagonize caffeine-induced seizures. 678 45

Picolinic, kynurenic, xanthurenic and anthranilic acids are metabolites of L-kynurenine which, when administered intraperitoneally (i.p.) antagonized (in descending order of potency) the seizures induced by intracerebroventricular (i.c.v.) injections of l-kynurenine sulfate in SHR and C57BL/6 mice. Picolinic and anthranilic acids were also effective after oral administration. Picolinic acid completely prevented seizures. Kynurenic acid, when injected i.c.v. prior to l-kynurenine sulfate, appeared to be more effective than after i.p. administration while picolinic and anthranilic acids were less effective. This suggest that the antikynurenine effect of metabolites of kynurenine (kynurenines) is related to different brain structures, i.e. kynurenic acid predominantly affects structures adjacent to ventricles (e.g. hippocampus, caudate nucleus) while picolinic and anthranilic acids act on other brain structures or the periphery. Xanthurenic, kynurenic and picolinic acids merely prolonged the latency of seizures induced by i.c.v. quinolinic acid (another metabolite of kynurenine) or by subcutaneous strychnine sulfate and i.p. pentylenetetrazole, and did not modify seizures induced by i.p. caffeine and thiosemicarbazide. This selective antagonism of the tested kynurenines against kynurenine might be an important anticonvulsant factor in kynurenine-dependent seizures. It is suggested that increased excretion of xanthurenic, kynurenic and picolinic acids in patients with convulsive states may be manifestations of compensatory processes.
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PMID:Antagonism of kynurenine-induced seizures by picolinic, kynurenic and xanthurenic acids. 686 8

When introduced intracerebroventricularly, quinolinic acid appeared to be the only kynurenine metabolite among those tested (L- and DL-kynurenine sulfate, kynurenic and nicotinic acids, nicotinamide) which induced locomotor excitement and clonic seizures in rats; in high dosage all exhibited convulsant action in mice. L-Kynurenine sulfate (500 micrograms) induced continuous rotation in rats around a longitudinal axis in one or other direction. It also potentiated the convulsant effect of strychnine sulfate and caffeine. Neither the excitatory amino acids, L-glutamic and L-aspartic acids nor the inhibitory amino acids, GABA, glycine and taurine induced excitement or seizures in rats but did in mice. In rats, GABA, glycine and taurine induced sedation, side position and discoordination. The convulsants, strychnine sulfate and pentylenetetrazole, induced seizures both in rats and mice. Differences between species may derive from the better access of intracerebroventricularly administered drugs to mouse hippocampus. Thus mice may be preferable for studies of this type on excitatory amino acids (including kynurenine pathway metabolites) and rats for those on inhibitory amino acids.
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PMID:Excitatory effects of kynurenine and its metabolites, amino acids and convulsants administered into brain ventricles: differences between rats and mice. 713 Sep 75

To our knowledge, the clinical course of acute caffeine poisoning in neonates has not been previously reported. Three full-term infants manifested CNS irritability after the parenteral administration of large doses of caffeine and benzoate sodium injection in the delivery room for respiratory depression. The infants received caffeine in doses that ranged from 36 to 136 mg/kg. On arrival in a regional newborn center, they exhibited one or more of the following symptoms: tachypnea, fine tremor of the extremities, opisthotonus, tonic-clonic movements, and nonpurposeful jaw and lip movements. The overdose of caffeine produced a clinical picture that suggested neonatal seizures and prompted therapy with anticonvulsants. A fourth infant (premature) attained a high plasma caffeine concentration, but this infant's symptoms were altered by intraventricular hemorrhage. The combination of caffeine overdose and perinatal asphyxia may precipitate or increase seizure activity in the neonate. Recognition of the potential toxic effects of caffeine overdose should guide patient care and stimulate further study to establish appropriate use of caffeine in the newborn infant.
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PMID:Acute caffeine overdose in the neonate. 737 58

A novel purine, (N6-2-(4-chlorophenyl)-bicyclo 2.2.2.-octyl-(3)-adenosine) EMD 28422 increases the binding of (3H) diazepam to benzodiazepine receptors in vivo within 10 min after intraperitoneal administration. This increase in (3H) diazepam binding is due to an increase in the number of benzodiazepine receptors (Bmax) rather than an altered affinity of the radioligand for receptor (Kd), EMD 28422 protects mice against pentylenetetrazole and caffeine-induced seizures and potentiates the anticonvulsant action of subeffective doses of diazepam in a dose-dependent fashion. Furthermore, EMD 28422 also produces a significant increase in punished responding in a conflict situation (rats), and a long-lasting, dose-dependent decrease in spontaneous motor activity (mice). In contrast, neither EMD 39011 nor adenosine (the two component molecules of EMD 28422) possess anticonvulsant properties at doses up to five mole-equivalents of EMD 28422. These data indicate that the purine EMD 28422 produces a spectrum of pharmacologic effects similar to the benzodiazepines, yet in contrast to the benzodiazepines (and other purines), increases benzodiazepine receptor number. Thus, EMD 28422 may represent the prototype of a class of synthetic purines exerting a unique neurochemical effect on benzodiazepine receptors and possessing several therapeutic actions of the benzodiazepines.
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PMID:Pharmacologic and behavioral effects of EMD 28422: a novel purine which enhances (3H) diazepam binding to brain benzodiazepine receptors. 739 62

The epileptogenicity of caffeine and aminophylline was studied in rats. Intraperitoneal administration of caffeine produced an immediate excitation and seizures followed by an encephalopathy. A progression from encephalopathy to seizures was observed following aminophylline administration. During the development of behavioral seizures, the EEGs showed a progression from fast activity isolated or bursts of spikes and/or sharp waves to full-blown epileptiform discharges. A wide spectrum of cardiac arrhythmias was observed during and following the seizures. Epileptiform activities ranging from isolated or bursts of spikes and/or sharp waves to continuous epileptiform discharges were observed following local application of the drugs to the cerebral cortex.
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PMID:Caffeine- and aminophylline-induced seizures. 747 2

Prior studies have shown that in younger depressives undergoing ECT whose seizure durations declined despite maximum settings on three different ECT devices, pretreatment with caffeine lengthened seizures and resulted in clinical improvement. Caffeine (half life, 140-270 minutes) was well tolerated even in patients with pre-existing cardiovascular disease. The purpose of this retrospective study was to determine the safety and efficacy of caffeine augmented ECT in elderly depressed patients. The charts of 14 elderly depressives (average age 75.6, range 59-83; 2 males, 12 females) who received caffeine-augmented ECT were reviewed. Patients pre- and post-ECT medications, blood pressure, pulse, and seizure times (cuff and EEG) for each ECT performed were noted. The following conclusions were drawn from our study: (1) Caffeine definitely increases the seizure length and was useful in our setting when the energy settings could not be increased anymore. (2) Caffeine augmentation inconsistently causes an increase in pulse rate, on average, in the elderly. (3) Caffeine inconsistently produces an increase in mean arterial pressure. (4) Caffeine did not consistently produce an increase in the maximum rate-pressure product. We conclude from this study that caffeine-augmented ECT is safe and effective in increasing seizure duration in the elderly. However, more research needs to be done to determine optimal dosing and tolerability.
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PMID:Safety and efficacy of caffeine-augmented ECT in elderly depressives: a retrospective study. 757 41

Early developmental exposure to caffeine in rats results in changes in brain excitability that persist to adulthood. The mechanism of these alterations is unknown. To identify potential neurotransmitter systems involved, we exposed neonatal rats to caffeine and determined seizure thresholds for chemoconvulsants active at different CNS receptors in the adult animal. Rats were unhandled (NH) or received by gavage (0.05 ml/10 g) either vehicle (water) or caffeine (15-20 mg/kg/day) for postnatal days 2-6. At age 70-90 days, each rat was infused intravenously (i.v.) with picrotoxin (PIC), bicuculline (BIC) [convulsants acting at the gamma-aminobutyric acid/benzodiazepine (GABA/BDZ) receptor], pentylenetetrazol [PTZ, possibly acting at both GABA/BDZ and N-methyl-D-aspartate (NMDA) receptors], caffeine (acting at adenosine receptors), strychnine (STR, acting at glycine receptors), or kainic acid (KA, acting at the NMDA receptor). Seizure thresholds were analyzed as a function of neonatal treatment and sex. Thresholds for caffeine, PTZ, PIC, and KA were increased as a function of neonatal caffeine exposure (p = 0.01, 0.02, 0.02, and 0.005, respectively). The thresholds for BIC and STR were not altered. There were also gender differences in seizure susceptibility. Thresholds for seizures produced by BIC, caffeine, PIC, and STR were higher in females (p = 0.005, 0.005, 0.001, and 0.0001, respectively), but were not different for seizures caused by PTZ. These results suggest that early developmental exposure to caffeine affects later seizure susceptibility. Moreover, some of these effects are gender specific.
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PMID:Neonatal caffeine exposure and seizure susceptibility in adult rats. 763 92

A variety of neurotransmitter receptor changes occur after a course of electroconvulsive seizures (ECS) in rats, including an increased density of adenosine A1 sites. Adenosine antagonism has been related to the proconvulsant action of methylxanthines such as caffeine. We determined tonic-clonic seizure duration in rats given ECS with caffeine (0-175 mg/kg, IP) after a course of one or six daily ECS. A single day of ECS did not affect the dose-dependent proconvulsant action of caffeine. After six daily ECS, the proconvulsant action of caffeine was reduced. After nine daily ECS, an A1 antagonist (8-cyclopentyl-1,3-dipropylxanthine) and an A2A antagonist (1-allyl-3,7-dimethyl-8-p-sulfophenylxanthine) showed reduced proconvulsant activity. The results suggest that the reduced proconvulsant action of caffeine after chronic ECS depends on adenosine antagonism.
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PMID:Reduced proconvulsant activity of caffeine in rats after a series of electroconvulsive seizures. 767 57


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