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

Endogenous cerebral prostanoids possess anticonvulsant properties. This study investigates possible age-dependent anomalies of prostanoid synthesis in the brain of seizure-prone DBA/2J (DBA2) mice as compared to sound stimulus-resistant CFLP mice. Irrespective of the age of the animals, a large increase of prostaglandin (PG) D2 and E2 in the brain of CFLP mice was observed in response to pentylenetetrazol (PTZ)-, or electroshock (ES)-induced seizures. Significantly less PGD2 and PGE2 was formed in the brain of DBA2 mice at day 21 after birth when subjected to PTZ or ES convulsions. At 42 days of age, however, this deficit of cerebral PGD2 synthesis in DBA2 mice disappeared concomitantly with the age-related decrease in audiogenic seizure (AS) susceptibility, whereas the deficit of PGE2 formation persisted. These results suggest that a deficiency of cerebral PGD2 synthesis may be one of the factors responsible for the AS susceptibility of the DBA2 mice. In contrast to PTZ or ES convulsions, acoustically induced seizures of the DBA2 mice were not accompanied by cerebral prostanoid synthesis. This supports the view that the pathways involved in AS are different from those involved in PTZ or ES models of epilepsy.
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PMID:Differential prostaglandin formation induced by convulsions in the brain of mice susceptible (DBA/2J) and resistant (CFLP) to acoustic stimulation. 232 14

CPP (3-(2-carboxypiperazine-4-yl)-1-phosphonate), and its unsaturated analogue, CPPene (3-(2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid), have potent anticonvulsant activity against sound-induced clonic seizures in DBA/2 mice. Following i.p. administration the protection is maximal at 1-2 h, and the ED50 values (mumol/kg) are: D(-)-CPPene, 1.54; D(-)-CPP, 2.75; D,L( +/- )-CPP, 4.36. Following oral administration the protection is maximal at 3-4 h and the ED50 (mumol/kg) values are: D(-)-CPPene, 40.19; D(-)-CPP, 65.80; D,L( +/- )-CPP, 108.1.
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PMID:Potent oral anticonvulsant action of CPP and CPPene in DBA/2 mice. 233 32

Inbred DBA/2 (D2) mice have an inherited susceptibility to audiogenic seizures (AGS), whereas inbred C57BL/6 (B6) mice are resistant to these seizures. AGS susceptibility is genetically associated with a reduction of a brain Ca2+-ATPase activity. A novel apparatus was used for monitoring simultaneously the electrical activity and ATP release from brain slices. The amount of extracellular ATP detected in hippocampal slices following the electrical stimulation of Schaffer collaterals is significantly greater in D2 mice than in B6 mice. We suggest that the increased level of extracellular ATP in D2 mice is associated with reduced brain Ca2+-ATPase activity.
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PMID:Increased amount of extracellular ATP in stimulated hippocampal slices of seizure prone mice. 253 11

CGS 19755 (cis-4-phosphonomethyl-2-piperidine-carboxylic acid), a competitive antagonist at N-methyl-D-aspartate (NMDA)-preferring receptors, blocked both NMDA-induced convulsions in normal CF1 mice and sound-induced wild running in seizure-prone DBA/2 mice. The ED50 values for CGS 19755 to produce these effects (in the range of 2 mg/kg i.p.) were at least 3-fold lower than those which impaired the traction reflex, an index of motor coordination. When administered p.o. by gavage, CGS 19755 had little or no effect in these test procedures. In an experimental model of anxiety in rats, CGS 19755 significantly increased conflict responding within a relatively narrow dose range (minimum effective dose, 1.73 mg/kg i.p.). At higher doses of CGS 19755, this effect appeared to be obscured by drug-induced reductions in overall responding. Potential muscle relaxant effects were also suggested by the generalization of CGS 19755 to diazepam discriminative stimuli (ED50 = 9.0 mg/kg i.p.) and by impaired rotorod performance (ED50 = 6.2 mg/kg i.p.) in rats. Although some resemblances were apparent between the behavioral effects of CGS 19755 and those of phencyclidine-type drugs, the phencyclidine-like behaviors appeared only at considerably higher doses of CGS 19755 than those associated with anticonflict activity, and only partial generalization of CGS 19755 to dexoxadrol was observed at high doses. CGS 19755 promises to be an important new research tool for investigating the function of brain NMDA receptors.
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PMID:Behavioral pharmacological profile of CGS 19755, a competitive antagonist at N-methyl-D-aspartate receptors. 254 31

5.7-Dinitro-quinoxaline-2.3-dione (MNQX) displaced [3H]glycine binding to cortical membranes but had no effect n [3H]3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid ([3H]CPP) binding. MNQX potently antagonized N-methyl-D-aspartate (NMDA)-evoked release of [3H]GABA from cultured cortical neurones, NMDA evoked spreading depression and NMDA depolarizations in the rat neo-cortex. All of these responses were reversed by addition of glycine to the perfusion media. These results suggested that MNQX is an antagonist at the strychnine-insensitive glycine receptor associated with the NMDA receptor/ionophore complex. Furthermore the compound was found to antagonise audiogenic seizures in DBA-2 mice indicating the potential of glycine antagonists of this type in anticonvulsant therapy.
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PMID:A potent antagonist of the strychnine insensitive glycine receptor has anticonvulsant properties. 256 Sep 79

The anticonvulsant activity of 5-chloro-4-(2-imidazolin-2yl-amino)-2,1,3-benzothiazole, tizanidine, was studied following intraperitoneal (i.p.) administration in DBA/2 mice (which show sound-induced seizures). Protection against sound-induced seizures was observed after tizanidine, (0.5-4 mg/kg i.p.). The ED50 values for suppression of the tonic, clonic and wild running phases of sound-induced seizures were 0.54, 0.76 and 1.43 mg/kg, respectively. This protective action was significantly reduced by pretreatment with aminophylline (25 mg/kg i.p.), yohimbine (1 mg/kg i.p.) or piperoxan (20 mg/kg i.p.). Methysergide, a serotonin antagonists, did not significantly reduce the anticonvulsant effects of tizanidine. The present experiments suggest an involvement of purinergic and adrenergic mechanisms in the anticonvulsant action of tizanidine.
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PMID:Antagonists of adenosine and alpha-2-adrenoceptors reverse the anticonvulsant effects of tizanidine in DBA/2 mice. 256 44

The specific binding of L-nicotine and alpha-bungarotoxin, two ligands which label different populations of putative nicotinic receptors, was determined in eight brain regions of 19 inbred mouse strains. The dissociation constants for L-nicotine (average = 2.26 nM) and alpha-bungarotoxin (average = 0.31 nM) did not vary significantly among the brain regions or strains. In contrast, significant variability among the maximal binding sites was observed between regions and among the strains within a region. Significant differences in L-nicotine binding were observed among the strains in midbrain, hindbrain, hippocampus, hypothalamus and colliculi, while little variability was noted in cortex or cerebellum. In general, those strains that had high L-nicotine binding in one region had high nicotine binding in the other regions. The strains clustered into two large groups: one group expressing relatively low binding and a second group expressing relatively high binding. Significant differences in alpha-bungarotoxin binding were observed in seven of the eight regions measured and, in general, those strains with high binding in one region tended to have high binding in the other regions. The strains clustered into three groups: those with low binding (DBA/1 and DBA/2), those with high binding (ST/b alone) and those with intermediate binding (the remaining 16 strains). The amount of binding of the two ligands did not correlate with each other. Comparison of nicotinic ligand binding with physiological response to nicotine suggests a relationship of L-nicotine binding with several responses observed after injection of low doses of nicotine and a relationship between alpha-bungarotoxin binding and nicotine-induced seizures.
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PMID:Variation of nicotinic binding sites among inbred strains. 258 9

DBA/2J mice were monaurally or binaurally tested for susceptibility to sound-induced seizure. Two seconds following the beginning of running, one group of binaurally tested mice had acoustic stimulation interrupted for 15 s. These mice later seized when the stimulation was readministered. Their seizure progression closely resembled the behavior exhibited by noninterrupted binaurally stimulated mice and did not shift to the biphasic motor pattern of monaurally stimulated subjects. We conclude that the single burst of running of a binaurally tested mouse is qualitatively different from either of the two bursts of running exhibited by monaurally tested mice.
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PMID:Independence of uniphasic and biphasic audiogenic seizure progressions in mice. 259 Jan 51

Non-competitive antagonists of the N-methyl-D-aspartate (NMDA) receptor have been evaluated as anticonvulsants against sound-induced seizures in DBA/2 mice. The ED50 values for protection against sound-induced clonic seizures 15 min following the intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration are: MK-801, ED50 = 0.5 nmol (i.c.v.); 0.14 mumol/kg (i.p.); phencyclidine, ED50 = 14 nmol (i.c.v.); 1.9 mumol/kg (i.p.); dextrorphan, ED50 = 35 nmol (i.c.v.); 18.5 mumol/kg (i.p.); tiletamine, ED50 = 40 nmol (i.c.v.); 5.6 mumol/kg (i.p.); SKF-10047, ED50 = 50 nmol (i.c.v.); 23.5 mumol/kg (i.p.); dextromethorphan, ED50 = 70 nmol (i.c.v.); 28.0 mumol/kg (i.p.); ketamine, ED50 = 110 nmol (i.c.v.); 15.5 mumol/kg (i.p.). The anticonvulsant effects of ketamine and tiletamine are of short duration (10-30 min), whereas the anticonvulsant effects of MK-801 and dextromethorphan last for 45 min or longer. The effects of phencyclidine, SKF-10047 and dextrorphan are of intermediate duration. Mild to moderate behavioural excitation is associated with the anticonvulsant activity of all the non-competitive NMDA antagonists. For MK-801, phencyclidine, dextrorphan, SKF-10047 and ketamine there is a close correlation between their relative anticonvulsant potencies and their potencies for displacing [3H]MK-801. The anticonvulsant effect is likely to be primarily mediated via NMDA antagonism at the PCP/MK-801 site.
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PMID:Non-competitive N-methyl-D-aspartate antagonists protect against sound-induced seizures in DBA/2 mice. 267 64

Abnormal function of serotonergic neurones may be involved in the age-related susceptibility of DBA/2J mice to generalised convulsions induced by auditory stimulation. We have measured 5-HT2 receptor binding sites and synaptosomal 5-HT uptake in 5 brain regions of DBA/2J mice at ages before, during and after their maximal susceptibility to audiogenic seizures and in age-matched C57 B1/6 mice, a strain resistant to audiogenic seizures at all ages. The number of 5-HT2 binding sites was 20% higher in the cerebral cortex of DBA/2J than C57 B1/6 mice at the time of maximal susceptibility of DBA/2J mice to audiogenic seizures but did not differ at other ages. The number of 5-HT2 binding sites did not differ between the two strains at the ages studied in forebrain, mid-brain, hippocampus and pons-medulla. A marked reduction in the number of 5-HT2 binding sites was apparent in the mid-brain, hippocampus and pons-medulla of both strains of mice between 13-15 days of age and 21-23 days of age. Synaptosomal 5-HT uptake did not differ significantly between DBA/2J and C57 B1/6 in any of the brain regions at the ages studied. The higher density of cortical 5-HT2 binding sites in DBA/2J mice may contribute to their susceptibility to sound-induced seizures.
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PMID:5-HT2 receptor binding and 5-HT uptake in mouse brain: developmental changes and the relationship to audiogenic seizure susceptibility in DBA/2J mice. 271 83


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