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

The effects of nifedipine, an antagonist of voltage-operated calcium channels, on the development of amygdala kindling and on the production of fully kindled seizures, stimulated from the amygdala, were investigated. Rats were treated daily with two doses (5 and 50 mg/kg, i.p.) of nifedipine during the development of kindling. Both doses of nifedipine retarded the development of kindled seizures and 50 mg/kg of nifedipine prolonged the latency to the occurrence of bilateral forelimb clonus. In contrast to these antiepileptogenic effects, however, both doses also increased the duration of afterdischarge. This resulted in a striking increase in the cumulative duration of afterdischarge, required to reach stage 4 and 5 seizures. Contrary to the results of a previous study, 50 mg/kg of nifedipine did not produce any significant effect on fully kindled seizures, regardless of the interval (5 min-24 hr) between injection and stimulation of kindling. These results suggested that although nifedipine inhibited the propagation processes of seizures during development of kindling, it appeared to increase the duration of epileptic activity at the kindling focus.
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PMID:Nifedipine has paradoxical effects on the development of kindling but not on kindled seizures in amygdala-kindled rats. 186 96

Although seizure models using systemic administration of the chemoconvulsant pentylenetetrazol (PTZ) for induction of generalized clonic seizures in rodents are widely employed to identify potential anticonvulsants, the important role of diverse technical, biological and pharmacological factors in interpretation of results obtained with these models is often not recognized. The aim of this study was to delineate factors other than sex, age, diet, climate, and circadian rhythms, which are generally known. For this purpose, experiments with 8 clinically established antiepileptic drugs were undertaken in the following PTZ models: (1) the threshold for different types of PTZ seizures, i.e., initial myoclonic twitch, generalized clonus with loss of righting reflexes, and tonic backward extension of forelimbs (forelimb tonus), in mice; (2) the traditional PTZ seizure test with s.c. injection of the CD97 for generalized clonic seizures in mice; and (3) the s.c. PTZ seizure test in rats. In rats, in addition to evaluating drug effects on generalized clonic seizures, a ranking system was used to determine drug effects on other seizure types. When drugs were dissolved in vehicles which themselves did not exert effects on seizure susceptibility, the most important factors which influenced drug potencies were: (1) bishaped dose-response curves, i.e., a decline in anticonvulsant dose-response at high doses of some drugs, leading to misinterpretations of drug efficacy if only a single high drug dosage is tested; (2) effects of route of PTZ administration (i.v. infusion vs. s.c. injection) on estimation of anticonvulsant potency; (3) species differences in drug metabolism; (4) differences in drug potencies calculated on the basis of administered doses compared to potency calculations based on 'active' drug concentrations in plasma; (5) qualitative and quantitative species differences in drug actions; (6) endpoints used for PTZ tests; (7) misleading predictions from PTZ seizure models. Analysis of anticonvulsant drug actions indicated that myoclonic or clonic seizures induced by i.v. or s.c. PTZ might be suitable for predicting efficacy against myoclonic petit mal seizures in humans, but certainly not to predict efficacy against absence seizures. Tonic seizures induced by PTZ were blocked by drugs, such as ethosuximide, which exert no effect on tonic seizures in humans. In order to reduce the variability among estimates of anticonvulsant activity in PTZ seizure models, the various factors delineated in this study should be rigidly controlled in experimental situations involving assay of anticonvulsant agents.
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PMID:The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. III. Pentylenetetrazole seizure models. 190 9

Abecarnil (ZK 112119; isopropyl-6-benzyloxy-4-methoxymethyl-beta-carboxylate) is a metabolically stable beta-carboline derivative with potent anxiolytic and few sedative and ataxic effects in rodents. The anticonvulsant and muscle relaxant actions of abecarnil have been evaluated in mice, rats, gerbils and baboons. Abecarnil raised the threshold for tonic electroconvulsions in mice after corneal but not after auricular application, had no effect on maximal electroshock-induced tonic convulsions triggered by either method, protected mice against the tonic hindlimb extension in PTZ-, picrotoxin- and 3-mercaptopropionate-induced seizures and blocked clonus after PTZ, DMCM (methyl-4-ethyl-6,7-dimethoxy-9H-pyrido-(3,4-b)-indol-3-carboxylate) and 3-mercaptopropionate. Abecarnil had no effect on convulsions induced by bicuculline and strychnine. Furthermore, abecarnil blocked kindled seizures after chronic administration of PTZ and FG 7142 (beta-carboline-3-carboxylic acid methylamide) and protected mice and rats against limbic convulsions induced by pilocarpine. Severity and afterdischarge duration of amygdala-kindled seizures were reduced in rats treated with abecarnil. Abecarnil also antagonized selectively convulsions induced by i.c.v. administration of kainate, but not those triggered by N-methyl-D-aspartate or quisqualate. In genetic models of reflex epilepsy, abecarnil was effective against sound-induced convulsions in DBA/2 mice, against air blast-induced generalized seizures in gerbils and against myoclonus in baboons Papio papio. The anticonvulsant effect of abecornil in a PTZ seizure model in mice was potentiated by ethosuximide, whereas no significant potentiation was found with diazepam, clonazepam, diphenylhydantoin, carbamazepine and phenobarbital. Electromyographic monitoring in a etorphine model of muscle rigidity in rats showed no or little muscle relaxant effect of abecarnil.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anticonvulsant action of the beta-carboline abecarnil: studies in rodents and baboon, Papio papio. 197 Mar 62

The effects of excitatory amino acid antagonists on convulsions induced by intracerebroventricular (i.c.v.) or systemic (s.c.) administration of the gamma-aminobutyric acidA (GABAA) antagonist bicuculline (BIC) were tested in mice. 3-[+/-)-2-Carboxypiperazin-4-yl)-propyl-1-phosphonate (CPP), 2-amino-7-phosphonoheptanoate (AP7) and (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cycloheptan-5,10-imine maleate (MK-801) were used as representatives of N-methyl-D-aspartate (NMDA) antagonists. gamma-D-Glutamylaminomethylsulphonate (gamma-D-GAMS) typified a preferential kainate (KA) antagonist, 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) represented a preferential quisqualate (QA) antagonist, and kynurenic acid (KYNA) was used as a mixed NMDA/KA antagonist. Bicuculline methiodide (BMI) induced clonic convulsions following i.c.v. administration with a CD50 of 0.183 nmol (range 0.164-0.204). The excitatory amino acid antagonists blocked clonic seizures induced by BMI in the dose of 0.224 nmol (approximately CD97) when coinjected into the lateral ventricle. CPP (ED50 0.0075 nmol) was the most potent anticonvulsant and was followed by AP7 (0.182 nmol), MK-801 (0.22 nmol), gamma-D-GAMS (0.4 nmol), KYNA (1.7 nmol) and CNQX (5.17 nmol). Muscimol (MSC), the GABAA agonist, blocked BMI-induced seizures with an ED50 of 0.25 nmol. Systemic (s.c.) administration of BIC induced in mice generalized seizures with a CD50 of 2.2 mg/kg (range 1.9-2.5) for clonus and CD50 of 2.4 mg/kg (range 2.2-2.7) for tonus.2+ the pathogenesis of seizures triggered by bicuculline in mice.
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PMID:Excitatory amino acid antagonists protect mice against seizures induced by bicuculline. 216 7

The role of the ventral hippocampal dentate granule neurons in the mu opioid receptor agonist-induced motor seizures and wet dog shakes was examined in this study. [NMe-Phe3-D-Pro4]morphiceptin (9.4 nmol) was injected into the left ventral hippocampus of rats 14 days after unilateral or bilateral colchicine (5 nmol/site) lesions of ventral hippocampal dentate granule cells and the subsequent behavioral and neuropathological responses were observed. [NMe-Phe3-D-Pro4]morphiceptin injected into control animals produced convulsions and numerous wet dog shakes that lasted for less than 1 h. [NMe-Phe-D-Pro4]morphiceptin-induced wet dog shakes were significantly reduced in unilateral colchicine-pretreated rats, and completely inhibited in bilateral colchicine-pretreated animals. In contrast, generalized motor seizures evoked by [NMe-Phe3-D-Pro4]morphiceptin were potentiated and prolonged in colchicine-pretreated animals as status epilepticus (sustained clonus of forepaws and head for more than 1 h) was observed in both unilateral and bilateral colchicine-pretreated animals but not in control rats. No morphological damage of granule or pyramidal cells was found in the ventral hippocampus of control animals following [NMe-Phe3-D-Pro4]morphiceptin injection. Colchicine treatment by itself produced a selective lesion of dentate granule cells. In colchicine-pretreated animals, [NMe-Phe3-D-Pro4]morphiceptin induced widespread seizure-related damage of CA3/CA1 pyramidal cells. These results suggest that dentate granule cells in the ventral hippocampus are essential for the elaboration of wet dog shakes. However, these neurons may play an inhibitory role in the spread of seizure activity within the hippocampus or limbic structures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ventral hippocampal dentate granule cell lesions enhance motor seizures but reduce wet dog shakes induced by mu opioid receptor agonist. 216 33

Myoclonus is a clinical term meaning a quick involuntary jerk, seen in normal subjects under certain circumstances, including sleep, and in certain disease states. It is important as a symptom that may impair function and as an indicator of neurological dysfunction. Not until patients with myoclonus and major functional disability were reported in the 1960s was attention given to understanding its basis and pharmacotherapy. Reports of myoclonus developing after anoxic brain injury, and its response to treatment with the serotonin precursor 5-hydroxytryptophan (5-HTP), drew special attention. Further experience showed that only a few patients with myoclonus benefit from 5-HTP therapy. Benzodiazepines (BDZs) are often helpful in the treatment of myoclonus. Their beneficial effects decline with chronic administration because of drug tolerance, and the theoretical basis for BDZ responses remains unclear. The relationships between myoclonus, clonus, and epilepsy are discussed, as is the possible contribution of slow signaling transmembrane receptors to synchronization of motoneuron firing, which is suggested as a hallmark of myoclonus. Myoclonus may originate in many CNS sites, but the brain-stem reticular formation is especially relevant to myoclonus. Brain-stem serotonin neurons have special influence on spinal motoneurons, on startle responses, and on myoclonus. Among 5-HT receptors, 5-HT1A receptors are related to some forms of myoclonus, although 5-HT2 receptors are also implicated. GABAA receptors are related to some forms of myoclonus. Blockade of GABAA receptors or GABA synthesis regularly evokes convulsive seizures, but administration of many GABA agonists and some GABA uptake blockers paradoxically may evoke myoclonus. Injection of GABA receptor blockers into some brain areas has anticonvulsant effects. Stimulation of GABAA receptors may therefore promote or antagonize myoclonus depending on which GABA receptors are involved, the state of the system, etc. The role of glycine receptors is well established in some animal models, but has yet to be clearly established for human myoclonus. Opiates may produce myoclonus when given intrathecally or in high dosage. The concept of excitant anesthetics and special function of certain GABA receptors is discussed.
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PMID:Myoclonus: analysis of monoamine, GABA, and other systems. 216 12

Bilateral microinjection of kainic acid (30-117 pmol) into the substantia nigra induced convulsive seizures resembling those elicited from limbic system structures. The convulsive seizures, which consisted of facial and forelimb clonus with rearing and falling, developed after a latency of more than 30 min and were preceded by wet dog shakes and non-convulsive seizure activity registered electroencephalographically. The convulsant effect of intranigral kainic acid was strictly dose-dependent (ED50 = 60 pmol) and anatomically site-specific. Stimulation of nigral neurons by focal application of agonists for NMDA or quisqualate receptors, or by focal application of the GABA antagonist, bicuculline, was without convulsant effects. The convulsant action of intranigral kainic acid was prevented by the focal application of kynurenic acid (100 nmol) but not by 2-amino-7-phosphonoheptanoic acid (AP-7) (25 nmol) or 7-chlorokynurenic acid (20 nmol), suggesting that the convulsant effect of kainic acid in the substantia nigra does not depend upon activation of NMDA receptors in this region.
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PMID:Selective stimulation of kainate but not quisqualate or NMDA receptors in substantia nigra evokes limbic motor seizures. 217 10

Direct electrical stimulation of either the dorsal or ventral hippocampal formation elicits wet dog shakes and overt seizures. Destruction of dentate granule cells in the dorsal hippocampal formation does not significantly reduce the number of wet dog shakes elicited by ventral hippocampal stimulation. However, destruction of dentate granule cells in the ventral hippocampus virtually eliminates wet dog shaking elicited by dorsal hippocampal stimulation. Destruction of either dorsal or ventral dentate granule cells lowers the threshold for eliciting forelimb clonus with rearing. These results suggest that dentate granule cells in the ventral hippocampus are essential for wet dog shakes elicited by intrahippocampal stimulation. However, dentate granule cells throughout the hippocampal formation appear to play an important inhibitory role in the spread of seizure activity within the hippocampus.
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PMID:Differential effects of colchicine lesions of dentate granule cells on wet dog shakes and seizures elicited by direct hippocampal stimulation. 223 60

The effect of intracranial microdialysis on brain glucose metabolism in control and kainic acid-treated rats was assessed by semi-quantitative [14C]2-deoxyglucose autoradiography. A dialysis fiber loop was implanted into the piriform cortex or a horizontal Vita fiber into the hippocampus, and 24 h later, fibers were perfused with Krebs-Ringer bicarbonate solution before and after injection of kainic acid (16 mg/kg, i.p.) [14C]2-Deoxyglucose was injected i.p. 3 h after the injection of kainic acid. Rats injected with kainic acid were initially lethargic and then proceeded through behavioral phases of staring, "wet-dog shakes", Straub tail, rearing, forepaw clonus, and, in some cases, tonic-clonic convulsions. Three hours after kainic acid, the fiber presence in the piriform cortex enhanced kainic acid-induced metabolic activity in areas adjacent to the fiber assembly, whereas the fiber in hippocampus attenuated kainic acid-induced metabolic activity in areas adjacent to the fiber assembly. The results indicate that intracranial microdialysis alters the already abnormal brain metabolism in a kainic acid-induced seizure state, but has no significant effect in the non-seizure control state.
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PMID:Effects of microdialysis on brain metabolism in normal and seizure states. 224 90

Multiple stimulation regimes with interstimulation intervals of 0.25-2 h were investigated in fully kindled rats as methods of testing the time course and potency of anticonvulsant drugs after a single administration. Protocols with conventional interstimulation intervals of 1-3 days were used for comparison. Prior to the drug experiments, the different stimulation regimes were examined in drug-naive, kindled rats in order to determine the extent of postseizure inhibition occurring with such protocols. All stimulations were carried out with a suprathreshold current of 500 microA. Using protocols with 3-9 stimulations within 8 h, seizure severity was relatively stable, but motor seizure duration was reduced in most experiments. Both decreases and increases were observed with respect to afterdischarge duration (ADD). The increases in ADD were primarily due to the appearance of 'secondary' afterdischarges with small amplitude, which were associated with immobility, intermittent facial clonus and head nodding. After a series of stimulations at short intervals, reduced seizure severity was observed after this series for at least 1 week, so that an interval of at least 2 weeks had to be interposed between multistimulation experiments in the same group of rats. When the effects of carbamazepine, 15 mg/kg, were determined with 4 different stimulation regimes, it was found that the anticonvulsant potency of the drug was higher in experiments with short interstimulation intervals compared to conventional protocols with interstimulation intervals of 1-3 days, indicating synergistic effects between the drug and postictal inhibition. Indication for such synergism was also found when the animals were only stimulated once daily during the drug experiments. With higher doses of carbamazepine or phenobarbital, 30 mg/kg, the difference between the stimulation protocols was less marked. Furthermore, the time course of anticonvulsant action determined with different stimulation regimes was similar. The data indicate that multistimulation regimes can be used in kindled rats to determine the time course following single administration of anticonvulsant drugs, but such protocols may lead to an overestimation of anticonvulsant potency.
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PMID:The effect of interstimulation interval on the assessment of anticonvulsant drug potency in fully kindled rats. 228 78


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