Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CONVULSIONS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,243 records · Page 69Linked to original sources
PubMed1988

Ontogenesis and properties of the convulsant recognition site(s) of the gamma-aminobutyric acid (GABA) receptor complex in chicken embryo.

Ontogenesis of the convulsant (picrotoxinin or t-butylbicyclophosphorothionate (TBPS] site(s) was defined in chicken embryonic brain with the radioligands [35S]TBPS and [3H]t-butylbicycloorthobenzoate [( 3H]TBOB). Binding of the radioligands is detectable from day 6 of incubation. The increase in binding after day 14 of incubation is due to an increase in the number of binding sites. The pharmacological properties of the embryonic recognition site(s) do not undergo significant changes during hatching based on the affinity of embryonic and chick brain membranes for [3H]TBOB; the rate of association and dissociation for TBOB; non-competitive inhibition of [3H]TBOB binding and modulation of 1R, alpha S-cis-cypermethrin interaction with the recognition site(s) by GABA; and inhibition of radioligand binding by endrin, picrotoxinin and TBPS. Early development and in vitro susceptibility of the recognition site to convulsive toxicants makes the embryo a possible target for a variety of drugs and environmental toxicants acting at this site.

Aging↗
PubMed1990

Inositolhexakisphosphate is convulsant in mice and rats in the nanomolar range.

The effect of i.c.v. administration of dodecasodium and dicalcium inositolhexakisphosphate (Na12IP6 and Ca2IP6, respectively) to mice and rats was studied. In mice, Na12IP6 (1-300 nmol) or Ca2IP6 (10-500 nmol) induced: ataxia, ground-hugging, tremor (often continuous), scratching, hyperlocomotion, wild running, myoclonic jerks, jumping, clonic muscle spasms, tonic seizure, followed by death or full recovery. The CD50 values for clonic seizures for Na12IP6 and Ca2IP6 were 16 and 49 nmol, respectively. The convulsant effect of Na12IP6 (15 nmol i.c.v.) was not blocked by pretreatment with D(-)-4-(3-phosphonoprop-2-enyl)-piperazine-2-carboxylate, but was dose dependently reduced by pretreatment with CaCl2 (30-60 nmol i.c.v.) and abolished by coadministration of CaCl2 (30 nmol) with Na12IP6 (i.c.v.). In rats, Na12IP6 (50 nmol i.c.v.) induced severe electroencephalographic seizures in the hippocampus and cortex. The potent convulsant effect of IP6 (administered i.c.v.) depends at least in part on a calcium-chelating action.

Animals↗
PubMed1992

ucb L059, a novel anti-convulsant drug: pharmacological profile in animals.

The anticonvulsant activity of ucb L059 ((S)-alpha-ethyl-2-oxo-pyrrolidine acetamide) was evaluated in a range of animal models. ucb L059 was active after oral and intraperitoneal administration in both rats and mice, with a unique profile of action incorporating features in common with several different types of antiepileptic drugs. The compound was active, with ED50 values generally within the range of 5.0-30.0 mg/kg, in inhibiting audiogenic seizures, electrically induced convulsions and convulsions induced chemically by pentylenetetrazole (PTZ), bicuculline, picrotoxin and N-methyl-D-aspartate (NMDA). ucb L059 retarded the development of PTZ-induced kindling in mice and reduced PTZ-induced EEG spike wave discharge in rats. The R enantiomer, ucb L060, had low intrinsic anticonvulsant activity, showing the stereospecificity of action of the molecule although the actual mechanism of action remains unknown. Neurotoxicity, evaluated with an Irwin-type observation test, the rotarod test and open-field exploration, was minimal, with only mild sedation being observed, even at doses 50-100 times higher than the anticonvulsant doses; at pharmacologically active doses, the animals appeared calm but slightly more active. ucb L059 thus presents as an orally active, safe, broad-spectrum anticonvulsant agent, with potential antiepileptogenic and anti-absence actions.

Acoustic Stimulation↗
PubMed1991

Differential response of rat brain polyamines to convulsant agents.

The polyamines putrescine (PUT), spermidine (SD) and spermine (SM) have been studied in rat brain after treatment with several convulsant agents. Kainic acid (10 mg/kg), picrotoxinin (1.5 mg/kg), pentylenetetrazol (60 mg/kg) and lindane (gamma-hexachlorocyclohexane) (60 mg/kg) were given to male Wistar rats. Twenty-four hours later, the animals were sacrificed and their brains removed. Cortical polyamines were analyzed by HPLC with fluorimetric detection of their respective dansyl derivatives, using 1,6-diaminohexane as internal standard for the measurements. Polyamine levels are not affected by short periods of time (30 min) of brain exposure to room temperature before freezing the samples, as compared to a quick procedure (less than 40 s from animal death). Kainic acid induced a 14-fold increase of cortical PUT with respect to control values, leaving unchanged the other polyamines. Lindane also increased cortical PUT (4-fold) without affecting SM or SD. Neither picrotoxinin, nor pentylenetetrazol groups were different from controls for any of the polyamines assayed. The results are discussed in relation to the possible mechanism of action of these convulsant agents and the role of the polyamines in cell injury.

Animals↗
PubMedDate not supplied

Effect of daily saline, drug or blank injections on the susceptibility to the convulsant effect of drugs.

The daily intraperitoneal injection to rats of doses of metrazol (30 mg/Kg), strychnin sulfate (1 mg/Kg) or picrotoxin (1.2 mg/Kg) that were initially subconvulsant, caused after a number of days which varied with the drug, clonic convulsions in a high percentage of the animals. However, after 18 daily injections of saline there was a similar increase of seizure susceptibility to the 3 drugs. The daily handling of rats as for injection, either followed or not by actual abdominal pricking (blank injection), had a similar though less pronounced effect. In animals that were housed in the same room where the others were tested, but which were not handled, the above mentioned doses of metrazol, strychnine and picrotoxin had no convulsant effect. These results indicate that the procedure of submitting rats to daily intraperitoneal injections is not as unconsequential as is usually thought to be, and that it may induce neurological changes.

Animals↗
PubMed1983

Strain differences in susceptibility to the convulsant actions of 3-carbomethoxy-beta-carboline.

NIH mice were found to be approximately three-fold more sensitive than NIH General Purpose mice to the convulsant actions of 3-carbomethoxy-beta-carboline. The convulsant action of 3-carbomethoxy-beta-carboline has been previously demonstrated to be mediated via an interaction with C.N.S. benzodiazepine receptors. The characteristics of the benzodiazepine receptor from the two strains appeared to be identical with respect to both binding affinity and capacity for [3H]3-carbomethoxy-beta-carboline and [3H]diazepam, as well as the relative decreases in apparent receptor affinity for [3H] 3-carbomethoxy-beta-carboline in the presence of 10 microM gamma-aminobutyric acid. Although the rate of degradation of 3-carbomethoxy-beta-carboline in plasma was similar in the two strains, a marked difference in brain levels of the drug (or an active metabolite) was observed after in vivo administration. These results suggest that pharmacokinetic, rather than pharmacodynamic factors are primarily responsible for the observed strain differences in sensitivity to 3-carbomethoxy-beta-carboline.

Animals↗
PubMed1983

Tonic convulsive thresholds and responses during the postnatal development of rats administered 6-hydroxydopamine or 5,7-dihydroxytryptamine within three days following birth.

The maturation of the electroshock tonic convulsive pattern and threshold was investigated in rats between the ages of 4 and 30 days following intracisternal injections of 6-hydroxydopamine (6-OHDA) on postnatal days 1 and 2; or 5,7-dihydroxytryptamine (5,7-DHT) after desipramine on postnatal day 3. In 6-OHDA treated rats decreases in brain norepinephrine (mean values of 55% of control) and dopamine (mean values of 17% of control) were associated with a large reduction in the convulsive threshold and intensification of the pattern on postnatal day 4. Whereas the reduction in catecholamine concentrations and the intensification of the pattern were still evident on postnatal day 30, the last day of testing, the threshold effect was not evident by postnatal day 15. Although 5,7-DHT reduced brain serotonin concentrations (mean values of 59% of control) as early as postnatal day 4, the pattern was not intensified until postnatal day 8, and the threshold was not reduced until postnatal day 21. These effects were still evident on postnatal day 30. The results demonstrate a sequential maturation of monoaminergic regulation in seizure susceptibility and severity, with an apparent transition from catecholaminergic to serotonergic regulation of the tonic threshold during the third postnatal week.

5,7-Dihydroxytryptamine↗
PubMed1995

Antagonism of isoniazid-induced convulsions by abecarnil in mice tolerant to diazepam.

The ability of the benzodiazepine receptor full agonist diazepam, the selective agonist abecarnil, and the partial agonist imidazenil to antagonize convulsions induced by isoniazid (200 mg/kg, S.C.) was studied in mice chronically treated with diazepam (3 mg/kg, i.p., three times daily) or abecarnil (0.1 or 1 mg/kg, i.p., three times daily or 6 mg/kg, S.C., daily). Diazepam induced tolerance to its own anticonvulsant effect. In contrast, chronic treatment with abecarnil failed to induce tolerance to its own anticonvulsant activity. Animals treated with abecarnil at 0.1 mg/kg developed cross-tolerance to imidazenil, whereas those treated with 1 mg/kg became less sensitive to diazepam. Mice chronically treated with abecarnil at 6 mg/kg showed almost complete tolerance to diazepam. Abecarnil was able to antagonize the convulsions elicited by isoniazid in diazepam-tolerant mice. These data indicate that chronic administration of abecarnil, unlike that of classical benzodiazepines, does not induce tolerance to its anticonvulsant effect, and that abecarnil overcomes tolerance induced by long-term treatment with the full agonist diazepam.

Animals↗
PubMed1985

Can drug effects on anxiety and convulsions be separated?

The effects of benzodiazepines, barbiturates, a series of novel putative anxiolytic compounds and anxiogenic compounds are reviewed in animal tests of anxiety and on experimentally-induced seizures. It is clear from the data that drug effects on anxiety and convulsions are not always in the same direction; certain compounds are apparently both anxiolytic and proconvulsant, others are anxiogenic and anticonvulsant, others have varied effects depending on the test situation. It is suggested that this work necessitates considerable revision of our traditional concepts of an "anticonvulsant." The extent to which drug-induced anxiety is correlated with weak epileptiform activity in the brain is discussed. Finally, the Discussion considers a number of possible mechanisms that could underlie the separation of drug effects on anxiety and convulsions that is observed.

Animals↗
PubMed1986

The convulsant and anticonvulsant effects of phencyclidine (PCP) and PCP analogues in the rat.

The pro- and anticonvulsant effects of phencyclidine (1-[1-phenylcyclohexyl]piperidine HCl, PCP), a number of its analogues, and SKF 10047 were investigated in rats. The PCP analogues were compounds produced by substitutions for the phenyl and piperidine rings of PCP and were selected to elucidate the structure-activity relationships existing between PCP and its pro- and/or anticonvulsant effects. All of the compounds, except ketamine, induced convulsions at high (12.8-25.6 mg/kg, i.v.), yet almost always sublethal doses. Ketamine failed to induce convulsions, even at lethal doses (51.2 mg/kg, i.v.). The acute pro- or anticonvulsant actions of PCP were then investigated. Rats were subjected to transorbital electroconvulsive shock subsequent to i.p. injections of saline or 0.625, 2.5, 5.0, 10.0 or 20.0 mg/kg PCP. It was found that PCP induced an acute, dose-dependent anticonvulsant effect. The acute pro- and/or anticonvulsant actions of the remaining compounds were then investigated by administration of electroconvulsive shock subsequent to i.p. injections of saline or one of two doses of each compound. The low and high doses of each compound were selected to be behaviorally equivalent to 2.5 and 10.0 mg/kg PCP i.p., respectively. With one exception, each dose of each drug induced an acute anticonvulsant action, with no difference in efficacy between the compounds tested. However, PCA (produced by substitution of an amine for the piperidine ring of PCP) induced a statistically greater anticonvulsant action at the higher, compared to the lower, dose. In addition, PCA was the only compound to eliminate all motor signs of the electrically induced seizure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Calcium-dependent actions of the convulsant barbiturate, CHEB, on transmitter release at the rat neuromuscular junction.

1. The effect of convulsant barbiturates on spontaneous and evoked acetylcholine release was studied at the rat neuromuscular junction in vitro. 2. The convulsant barbiturates (+)-5-(1,3-dimethylbutyl)-5-ethyl barbituric acid [(+)-DMBB], 5-(2-cyclohexylideneethyl)-5-ethyl barbituric acid (CHEB), 5-ethyl-5-(3-methylbut-2'-enyl) barbituric acid (3M2B) and 5-ethyl-5-(1,3-dimethylbut-1'-enyl) barbituric acid (1,3M1B) all produced a concentration-dependent increase in miniature end-plate potential (MEPP) frequency. 3. With CHEB (100 microM) this increase in MEPP frequency was found to be dependent on the [Ca2+]o. CHEB in 0.5 mM [Ca2+]o did not alter MEPP amplitude, but in 1.3 and 2.5 mM [Ca2+]o CHEB significantly reduced the amplitude. 4. At a [Ca2+]o of 0.5 mM, CHEB produced an increase in both EPP amplitude and quantal content, while at 1.3 mM [Ca2+]o CHEB did not alter EPP amplitude or quantal content. 5. The plot of log quantal content vs log [Ca2+]o showed a parallel shift to the left in the presence of 100 microM CHEB. This change occurred without any alteration in the maximum quantal content. This suggests that the enhancement of transmitter release may be mediated by an effect on calcium fluxes in the pre-junctional nerve terminal.

Acetylcholine↗
PubMed1987

Convulsant action of morphine, [D-Ala2, D-Leu5]-enkephalin and naloxone in the rat amygdala: electroencephalographic, morphological and behavioural sequelae.

Morphine hydrochloride (25-200 nmol), [D-Ala2, D-Leu5]enkephalin (10-200 nmol) and naloxone hydrochloride (100-1000 nmol) were injected unilaterally into the rat amygdala and the following electrographic, behavioural and neuropathological responses were studied. Microinjections of low doses of morphine (25-50 nmol) resulted in behavioural alterations characterized by staring, gustatory automatisms and wet shakes, whereas higher doses additionally produced motor limbic seizures and status epilepticus. The first changes in the electroencephalogram appeared in the amygdala immediately after the administration of morphine and rapidly spread to hippocampal and cortical areas. Electrographic alterations consisted of high voltage fast activity, spiking, bursts of polyspiking, electrographic seizures and periods of postictal depression. Neuropathological analysis of frontal forebrain sections by means of light microscopy revealed widespread, seizure-related damage confined to amygdala, olfactory cortex, thalamus, hippocampal formation, neocortex and substantia nigra. Pretreatment of animals with naloxone, 2-20 mg/kg s.c., as well as simultaneous microinjection of the non-convulsant dose of naloxone, 100 nmol, with morphine, 100 nmol, into the amygdala failed to block the development of convulsant activity and seizure-related brain damage produced by the opiate. In contrast, diazepam, 10 mg/kg i.p., when administered prior to the microinjection of morphine into the amygdala, abolished the epileptogenic effects of the drug. [D-Ala2, D-Leu5]Enkephalin, 10-200 nmol, elicited electrographic and behavioural responses similar to those seen after low doses of morphine, when administered into the amygdala. High voltage fast activity, single spikes, bursts of polyspiking, electrographic seizures and periods of postictal depression were seen in the electroencephalogram, but no behavioural signs of motor limbic seizures could be detected. The only behavioural correlates of epileptiform electrographic activity were wet shakes, myoclonic head twiches and gustatory automatisms. The examination of frontal forebrain sections from rats receiving [D-Ala2, D-Leu5]enkephalin revealed no morphological changes. Pretreatment of rats with either naloxone, 2 mg/kg, or diazepam, 10 mg/kg, blocked the development of behavioural and electrographic sequelae of the peptide. Naloxone, 100-1000 nmol, when microinjected into the amygdala, produced electrographic, behavioural and morphological alterations resembling those seen after high doses of morphine.(ABSTRACT TRUNCATED AT 400 WORDS)

Amygdala↗
PubMed1991

Magnesium sulphate subcutaneously injected protects against kainate-induced convulsions and neurodegeneration: in vivo study on the rat hippocampus.

Kainate, an agonist of a unique subclass of glutamate receptors (kainate receptor), was injected intracerebroventricularly in rats to induce convulsive reactions and hippocampal damage in order to model glutamate-mediated brain injury. Rats treated with magnesium sulfate (subcutaneously injected, up to 600 mg/kg) were found to be protected from kainate neurotoxicity depending on the dose and time of application. Results were largely consistent with those obtained previously by using quinolinate as an excitotoxic N-methyl-D-aspartate-receptor agonist. Magnesium is discussed as being a natural and relatively safe therapeutic in cases of glutamate-induced (hypoxic, ischemic, traumatic, or convulsive) disorders of the brain.

Animals↗
PubMed1989

Long-term effects of the administration of the convulsive substance DL-methionine-DL-sulfoximine to the rabbit.

Methionine sulfoximine (MSO) is a centrally acting neurotoxin which inhibits the glutamate metabolism enzymes and has convulsive properties. Administration of a small dose of MSO to rabbits, either intravenously or intracerebroventricularly, except for the already known convulsive effects, may also be responsible for hind leg myopathy (rigid paralysis with histological findings resembling myositis) which sets in by the 4th day after MSO administration.

Animals↗
PubMedDate not supplied

Experimental secondarily generalized convulsive status epilepticus induced by D,L-homocysteine thiolactone.

Secondarily generalized convulsive status epilepticus was induced by intraperitoneal (i.p.) injection of D,L-homocysteine thiolactone to rats with actively epileptogenic cobalt lesions in motor cortex. This induced focal motor seizures which secondarily generalized. Control animals not treated with antiepileptic drugs had a mean of 18.3 generalized convulsions over a mean period of 103.8 min. Electrographic patterns seen during status epilepticus are described and are very similar to those seen during human status epilepticus. Phenytoin, phenobarbital, diazepam and lorazepam were all effective in arresting the generalized seizures when given i.p. after the second such seizure. Efficacy was serum drug concentration dependent. Concentrations effective in arrest of generalized seizures in this model are similar to those reported to be effective in the treatment of human status epilepticus. Diazepam ED50s for control of generalized tonic-clonic seizures and for arrest of all seizure activity were determined.

Animals↗
PubMedDate not supplied

Monosodium L-glutamate-induced convulsions: changes in uptake and release of catecholamines in cerebral cortex and caudate nucleus of adult rats.

Adult rats (60 days old) were injected intraperitoneally with 5 mg/g monosodium L-glutamate (MSG). During the convulsive period (1 h after injection), uptake and release of [3H]norepinephrine (3H-NE) and [14C]dopamine (14C-DA) were measured in a crude synaptosomal fraction and in slices of cerebral cortex and caudate nucleus, respectively. A significant reduction of 3H-NE uptake was detected in cortical slices (by 42%) and in synaptosomal fraction (by 33%) of rats treated with MSG, whereas K+- stimulated 3H-NE release was decreased by 32% and 39% in brain slices and in a synaptosomal fraction of cerebral cortex, respectively, in comparison with animals injected with 0.9% NaCl aqueous solution (PSS). In the caudate nucleus, 14C-DA uptake was increased by 100% in brain slices and by 36% in the synaptosomal fraction following MSG administration, whereas K+- stimulated 14C-DA release was enhanced by 80% in slices and by 25% in synaptosomes as compared to PSS-injected rats. Data suggest that catecholaminergic neurotransmission may play an important role in the etiopathology of convulsions in the experimental model using MSG.

Animals↗
PubMedDate not supplied

Relationships between benzodiazepine receptors, impairment of GABAergic transmission and convulsant activity of beta-CCM: a PET study in the baboon Papio papio.

Central type benzodiazepine receptors were studied in vivo by positron emission tomography in brain areas of 2 different groups of the baboon Papio papio: non-photosensitive (group 1) and those with an allylglycine-induced decrease in GABA-mediated inhibition (group 2). Further, a naturally photosensitive Papio papio (+3 level of photosensitive response) was compared to both groups. Regional brain binding of the specific benzodiazepine receptor ligand, [11C]Ro 15-1788, was not significantly different between groups 1 and 2. In addition, the data from the naturally photosensitive Papio papio did not seem to differ markedly from groups 1 and 2 either. Pharmacological effects of increasing doses of beta-CCM (0.05-3 mg/kg i.v.) and regional benzodiazepine receptor occupancy by the drug were simultaneously studied using electroencephalographic activity recording and positron emission tomography. A positive correlation was observed between the degree of photosensitivity of the baboon and sensitivity to the action of beta-CCM, with increasing convulsant efficacy of beta-CCM in going from group 1 to the naturally photosensitive baboon, then to group 2. Dose-related displacement curves of [11C]Ro 15-1788 binding by beta-CCM revealed that reduction in brain GABA concentration did not modify the inhibitory potency of beta-CCM on [11C]Ro 15-1788 binding in cerebral cortex. This suggests a lack of detectable in vivo allosteric effects of GABA on beta-CCM binding during beta-CCM-induced seizures. Thus, a given dose of beta-CCM displayed increasing pharmacological potency in going from baboons with the lowest photosensitivity to those with the highest, whereas benzodiazepine receptor occupancy by beta-CCM was similar in the cerebral cortex of the different baboons. Conversely, a given level of convulsant activity of beta-CCM was related to a different benzodiazepine receptor occupancy by the drug, depending on the photosensitivity of Papio papio. A given dose of a drug may, thus, have a different pharmacological potency when occupying the same number of receptors, depending on the physiopathological state of the subject.

Animals↗
PubMed1996

Arrest of seizure progression during electrical kindling in guinea-pigs with prior pentylenetetrazol-induced convulsions.

A number of comparative differences in the kindling phenomenon have been observed between guinea-pigs and rats. These differences likely reflect different mechanisms underlying brain plasticity. In this study, guinea-pigs were used to examine the kindling transfer phenomenon between peripheral pentylenetetrazol injection and electrical kindling of the amygdala. The changes in afterdischarge characteristics and behavioural seizures during electrical kindling were compared between animals that had experienced three PTZ-induced convulsions and PTZ-naive controls. We report that on the first electrical kindling session the PTZ-convulsed guinea-pigs displayed lower AD thresholds, enhanced AD durations and seizures, but that their seizures did not progress with repeated daily kindling stimulation.

Animals↗