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

The author carried out studies on male white rats and examined the effect of imidazol, papaverine and theophyline (drugs affecting the activity of phosphodiesterase), singly or in correlation with GAMA and diazepam on picrotoxic seizure threshold (PSAT). He found that imidazol had various effects on PSAT in accordance with the interval of application and antagonized the effects of GAMA. Papaverine in low doses was ineffective, but in higher doses lowered PSAT; it antagonized the effect of GAMA, elevating the threshold. Papaverine in combination with CAMF antagonized the effect of GAMA, elevating the threshold. Theophyline lowered PSAT; it did not influence the effects of the combined application of GAMA and DIA. He thinks that the obtained changes in PSAT could partly be connected with the mediating influence of imidazol, papaverine and phe theophyline on cerebral phosphodiesterase both after their single application and after examination of their correlations with GAMA or DIA, used singly or in comibination, and partly with their own pharmacologic action.
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PMID:[Effects of imidazole, papaverine and theophylline on the picrotoxin convulsion-seizure threshold. The correlation with gamma-aminobutyric acid (GABA) and diazepam]. 69 66

In experiments on male albino rats and mice a study is made of the effects of imidazol which is a phosphodiesterase stimulator, papaverine which inhibits phosphodiesterase and histamine which stimulates adenylate cyclase, on the convulsive-seizure reactivity. The substances are introduced intraventricularly and intracerebroventricularly, imidazol also intraperitoneally in different doses and at different intervals before the convulsive agent. Electrical, pentylenetetrazol (Cor) and strychnine convulsion models are used. The effect of imidazol on the spontaneous cortical bioelectrical activity is studied throuth its i. v. administration in rabbits. Imidazol markedly increases the convulsive reactivity, and in large doses it alone results in electrographic and motor convulsions. Paperine slightly lowers the convulsive-seizure reactivity only in pentylenetetrazol convulsions. The results obtained and their comparison with the results of previous experiments of ours with other drugs affecting the cyclic adenosinemonophosphate (cAMP) system, such as lithium, haloperidol, caffeine and theophyline, do not permit to assume a considerable significance of the influence of these substances (in the doses tested) on the cAMP system in the mechanisms of their effects on the convulsive-seizure reactivity.
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PMID:Experimental study of the effects of imidazol, papaverine and histamine on convulsive-seizure reactivity. 101 6

The effect of caffeine when combined with cocaine or amphetamine was studied in rats. Animals were pretreated with intraperitoneal vehicle (normal saline [NS]) or caffeine 100 mg/kg, then challenged with intraperitoneal cocaine (0, 35, 50, 70, or 90 mg/kg) or intraperitoneal d-amphetamine (0, 15, 25, 35, or 42 mg/kg). Animal behavior, time to, and incidences of seizures and death were recorded. This dose of caffeine alone did not cause seizures or death. Caffeine pretreatment significantly increased the incidence of overt seizures induced by either cocaine or amphetamine. Caffeine increased the incidence of cocaine-induced death from 10% to 90% at the 70 mg/kg cocaine dose (P less than .01). Caffeine increased amphetamine-induced death from 0% to 80% at 15 mg/kg (P less than or equal to .01), 10% to 70% at 25 mg/kg (P less than or equal to .01), and 30% to 80% at 35 mg/kg (P less than or equal to .01). To investigate mechanisms, additional animals were pretreated with the adenosine agonist, 2-chloroadenosine (2.5 and 10 mg/kg), before being challenged with NS, 90 mg/kg cocaine, or 42 mg/kg amphetamine. Pretreatment with 2-chloroadenosine had no affect in reducing cocaine or amphetamine toxicity. Combination pretreatment with caffeine and 2-chloroadenosine potentiated cocaine toxicity. The phosphodiesterase inhibitor, pentoxifylline, did not potentiate cocaine toxicity. The authors conclude that caffeine potentiates the acute toxicity of both cocaine and amphetamine, and that the failure of 2-chloroadenosine to alter this suggests that the toxicity of the stimulants cocaine and amphetamine may be modulated by nonspecific rather than specific adenosine- or phosphodiesterase-induced mechanisms.
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PMID:Potentiation of cocaine and d-amphetamine toxicity with caffeine. 158 30

The mechanism of action of aminophylline in prolonging seizures was tested in amygdala-kindled rats. Aminophylline prolonged the afterdischarge duration of kindled seizures. This seizure-prolonging action of aminophylline was strongly antagonized by the adenosine A1 agonist cyclohexyladenosine and partially antagonized by the benzodiazepine partial agonist RO 15-1788. However, the specific benzodiazepine antagonist CGS 8216 did not affect the seizure-prolonging action of aminophylline. Also, the potent anticonvulsant effect of diazepam on kindled seizures, which was completely antagonized by CGS 8216, was unaffected by aminophylline. Furthermore, a range of benzodiazepine inverse agonists, GABA antagonists, phosphodiesterase inhibitors and xanthines did not prolong afterdischarge durations. These results demonstrate that the seizure-prolonging action of aminophylline is due to block of A1 adenosine receptors since it is prevented by adenosine A1 agonists.
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PMID:Adenosine receptor antagonism accounts for the seizure-prolonging effects of aminophylline. 221 1

Repeated injection of an initially subconvulsive dose of cAMP into the rat amygdala (AM) produced progressive seizure development similar to that of electrical kindling. The chemical kindling occurred in a dose-dependent manner. Furthermore, when cAMP was combined with EDTA, a strong inhibitor of cAMP phosphodiesterase, the seizure development was remarkably facilitated. When the animals that had been chemically kindled were subjected to electrical kindling, they rapidly developed seizures. These results, together with those previously published, suggest that cAMP participates in the seizure development induced by AM kindling.
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PMID:Chemical kindling induced by cAMP and transfer to electrical kindling. 254 52

In ventilated rats, levels of phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP2), diacylglycerol (DAG), triacylglycerol (TAG), free fatty acids (FFA) and phosphatidic acid, as well as their fatty acid contents, were measured in forebrain tissue after 1, 20 and 60 min of seizures induced by bicuculline. Cerebral energy state was also measured. PI decreased progressively throughout 60 min of seizures, whereas the levels of PIP and PIP2 did not change. DAG increased modestly and persistently. FFA increased markedly during the early seizure period, but decreased later. Following an initial drop, TAG rose above control. Phosphatidic acid did not change. The levels of ATP and energy charge potential decreased slightly and lactate accumulated. Stearic acid (18:0) and arachidonic acid (20:4) primarily accounted for the changes in the levels of the lipids. At the onset of seizures, the decrease of 18.0 and 20:4 in PI occurred in parallel with an enrichment of these fatty acids in FFA and DAG. Despite the fact that the losses of 18:0 and 20:4 from PI were quantitatively similar to each other at all times examined, the increase in free 18:0 was much larger than the increase in free 20:4 at 20 min of seizures. Concurrently there was a rise of 20:4 in TAG. As the FFA levels declined thereafter, 20:4 and docosahexaenoate (22:6) in TAG continued to increase. The results are consistent with the view that seizure activity stimulates the hydrolytic breakdown of brain phosphoinositides--the pathway catalyzed by phosphodiesterase of the phospholipase C type followed by lipases, and probably the pathway catabolized by phospholipases A as well. Preferential incorporation of polyunsaturated fatty acids into TAG-acyl residues may represent a mechanism to reduce the level of their free forms when the latter are produced in large amounts.
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PMID:Cerebral phosphoinositide, triacylglycerol and energy metabolism during sustained seizures induced by bicuculline. 303 62

At the onset of pentylenetetrazole induced convulsions, the adenylate cyclase activity and phosphodiesterase activity were increased. The former was markedly stimulated in the brain stem of rats. In the cerebral cortex and brain stem, the glucose level was significantly decreased, and the concentration of glucose-6-phosphate was increased. However, the definite changes in energy reserve system of the brain could not be observed at the onset of penetylentetrazole induced seizures. The present study revealed some correlation between pentylenetetrazole convulsions and the adenylate cyclase activity and glycometabolism.
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PMID:Biochemical aspects of pentylenetetrazole induced seizure. 629 19

To elucidate the intracellular mechanism of the bursting activity which is characteristic of seizure discharge, the behavior of the intracellular cyclic nucleotide and the intracellular calcium during pentylenetetrazole (PTZ)-induced bursting activity in snail neurons was investigated. Cyclic AMP was increased about 3-fold by the incubation of ganglia with PTZ. The effect of PTZ on phosphodiesterase activity measured using either cyclic AMP or cyclic GMP as substrate showed a slight increase in cyclic AMP phosphodiesterase activity. The release of calcium from the lysosome fraction was increased by the incubation of ganglia with dibutyryl cyclic AMP. Protein kinase activity was stimulated by the incubation of ganglia with PTZ. Adenylate cyclase activity was stimulated by the incubation of ganglia with PTZ. These findings suggest that PTZ-induced bursting activity in snail neurons is initiated by an intracellular increase of cyclic AMP, which promotes calcium release from lysosomes and induces protein kinase activation.
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PMID:Behavior of intracellular cyclic nucleotide and calcium in pentylenetetrazole-induced bursting activity in snail neurons. 630 20

The shaking pup, a canine mutant, carries a point mutation in the myelin proteolipid protein (PLP) gene that causes dysmyelination of the central nervous system (CNS) with resultant tremor, seizures, and other persistent neurological deficits. The developmental potential of glial cells in the shaking pup CNS and peripheral nervous system (PNS) was evaluated by quantitative analysis of the expression of several glial-specific genes. All of the myelin-associated genes demonstrated developmental patterns of expression similar to those observed in the controls, but at significantly reduced levels. Expression of the genes for the major CNS myelin proteins, PLP and the myelin basic protein, are most dramatically affected in the shaking pup, although reduced expression levels are observed for other oligodendrocyte-specific genes such as 2',3'-cyclic nucleotide 3'phosphodiesterase and glucose phosphate dehydrogenase. The pattern of gene expression in the shaking pup indicates that the oligodendrocytes experience an inhibition in development after the myelination program has begun. There appears to be little evidence for an astrocytic response to the dysmyelinating condition at the RNA level, but we present evidence for ectopic expression of P0 mRNA in the CNS. Expression of the P0 and PLP genes in the sciatic nerve appears to be normal, reinforcing previous reports that PNS myelination is unaffected by the mutation in the PLP gene.
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PMID:Molecular analysis of glial cell development in the canine 'shaking pup' mutant. 889 46

Despite its potent proconvulsant effects in vitro, the adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) does not induce seizures when administered in vivo. This contrasts with the effects of less selective adenosine antagonists such as theophylline or cyclopentlytheophylline, and led us to reexamine the nature of DPCPX-induced epileptiform activity. In the present study, we report that proconvulsant effects of bath-applied DPCPX in rat hippocampal slices are only observed after a preceding stimulus such as NMDA receptor activation or brief tetanic stimulation. While this may be due to the absence of a basal "purinergic tone", the relatively high interstitial concentrations of adenosine present in the slice suggest that access of the drug to A1 receptors may instead be prevented by tightly coupled endogenous adenosine, with the ternary adenosine-A1 receptor-G protein complex stabilised in the high-affinity conformation by a coupling cofactor. This implies that a substantial percentage of adenosine A1 receptors are inactive under physiological conditions, but that access of adenosine A1 receptor antagonists may be facilitated under pathological conditions. Once induced, DPCPX-evoked spiking persists for long periods of time. A "kindling" effect of A1 receptor blockade is unlikely, since persistent spiking is not usually observed with less selective A1 antagonists even after prolonged application. Alternatively, endogenous adenosine released during increased neuronal activity may activate A2 receptors during selective A1 blockade. The most important factor determining the duration of DPCPX-induced spiking, however, may be a persistence of the drug in the tissue and subsequent access to the A1 receptor via a membrane-delineated pathway, since DPCPX-induced spiking could be shown to decrease markedly after a transient superfusion of theophylline. This hypothesis, which implies that the apparent affinity of adenosine antagonists for the A1 receptor is in part a function of their membrane partitioning coefficient, is supported by a close correlation between alkylxanthine logP values obtained from the literature and their Ki value at A1 receptors, but not at the enzyme phosphodiesterase, whose xanthine binding site is presented to the cytosol. The implications for the therapeutic value of purinergic drugs are discussed.
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PMID:Alkylxanthine adenosine antagonists and epileptiform activity in rat hippocampal slices in vitro. 906 16


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