Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Local blood flow, ECoG and single cortical neurone activity were recorded simultaneously from single microelectrodes in 17 cats. Seizures were induced by repeated intravenous injections of pentylenetetrazol (PTZ, 10-20 mg/kg) or by local application of 1 M Na-penicillin. Seven to 20 sec after appearance of burst activity in cortical neurones and ECoG, focal flow increased up to 300% of control. The extent of this flow increase was significantly correlated with the change in firing rate of the neurones. With cessation of seizure activity the flow returned to or below control values. Forty to 70 mg/kg PTZ caused status epilepticus with high voltage rhythmic discharges lasting 30 min-2 h. In 3 cats with status, the flow decreased below control despite persisting seizures, indicative of uncoupling between activity and flow. The delayed coupling between activity and flow during drug-induced seizures indicates a metabolic mediator. Uncoupling observed in cases with long lasting seizures may be due to brain oedema following increased permeability of the blood-brain barrier.
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PMID:Coupling between neuronal activity and focal blood flow in experimental seizures. 8 43

The in vivo effects of phenytoin (diphenylhydantoin, Dilantin) and the experimental anticonvulsant, eboracin, a substituted indenopyrrole, were compared in mice. Pretreatment with varying dosages of either agent followed by challenge with the chemoconvulsant pentylenetetrazol (Metrazol) indicated that eboracin provided slightly less protection against seizures than phenytoin and was much less toxic. Intermediate doses of either agent led to a form of clonic status epilepticus which persisted for an average of 18 min in phenytoin-treated and 58 min in eboracin-treated mice. Pretreatment with higher or lower doses did not lead to these manifestations. Animals in which this syndrome had been induced should be of value in studies of the chemistry and physiology of the clonic state.
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PMID:Comparison of anticonvulsive properties of eboracin and phenytoin in mice. 397 47

With the six convulsants studied (Soman, intrahippocampal penicillin, bicuculline, pentylenetetrazol, picrotoxin and strychnine), the anatomical distribution of changes in local cerebral glucose utilization was related to the type of seizure observed. Strychnine induced a few very intense motor convulsions during the 2-deoxyglucose experimental period without having a major effect on brain local cerebral glucose utilization, in support of the view that its actions are predominantly in the spinal cord. Pentylenetetrazol and picrotoxin induced intermittent intense seizures and marked increases in local cerebral glucose utilization in the globus pallidus and substantia nigra. Soman, intrahippocampal penicillin and bicuculline all induced persistent status epilepticus associated with increases in local cerebral glucose utilization in many brain areas; those with striking increases in glucose use include: cortical areas, the limbic system, basal ganglia and substantia nigra. The glucose use changes produced by Soman, penicillin and bicuculline greatly exceeded those induced by pentylenetetrazol and picrotoxin. Activation of the substantia nigra and basal ganglia occurred with all centrally mediated convulsions and with status epilepticus there was also marked activation of cortical and limbic structures.
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PMID:Changes in local cerebral glucose utilization induced by convulsants. 399 Sep 60

Altered cardiovascular function in status epilepticus may contribute to mortality and morbidity in patients. We investigated changes in cardiac output and regional hemodynamics during 2 h of recurrent PTZ-induced seizures in anesthetized, paralyzed rats using radioactive microspheres, thermodilution methods, and the pulsed Doppler technique. Cardiac output fell 30-60% during recurrent seizures in 17 of 27 animals. The fall in cardiac output was sudden in onset and occurred primarily in association with seizures accompanied by prolonged increases in MABP but no change in central venous pressure. Total peripheral resistance (TPR) rose during early seizures in association with vasoconstriction of renal and certain splanchnic vascular beds. Ictal increases in TPR became attenuated during late seizures, due to failure of renal and splanchnic beds to constrict. Therefore, derangements in both cardiac and vascular function occur during late seizures. These derangements may contribute to both cerebral hypoperfusion and sudden death in status epilepticus.
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PMID:Cardiac output and regional hemodynamics during recurrent seizures in rats. 828 38

Pentylenetetrazol (PTZ)-induced status epilepticus (SE) leads to acute and long-term metabolic decreases in specific brain regions of rats at 10 (P10) or 21 days after birth (P21). These decreases are not related to apparent neuronal damage. Therefore, to better understand the neuronal activation and stress response to PTZ in immature rats, we mapped the expression of c-Fos and of the 72 kDa heat-shock protein (HSP72) in the same model of severe SE induced by the repetitive i.p. injections of subconvulsive doses of PTZ. Rats were sacrificed either at 2 or 24 h after the onset of SE in order to reveal c-Fos immunoreactivity, and at 24 and 72 h for HSP72 expression. Hematoxylin-eosin staining was performed at 24, 72 and 144 h after SE. The expression of c-Fos at 2 h after SE was more marked at P21 than at P10 and was prominent at both ages in the hippocampal dentate gyrus, cerebral cortex and amygdala. Some immunoreactivity was also present in the hypothalamus, thalamus and a few brainstem and cerebellar regions at both ages. There was a good relation between the regions expressing c-Fos and those exhibiting acute metabolic decreases at P21. Conversely, PTZ seizures did not lead to any expression of c-Fos at 24 h after SE or of HSP72 at 24 or 72 h at any age. Cell density was not affected by PTZ-induced SE at any age and at any time. These results suggest that c-Fos is a useful marker of neuronal activation induced by severe and prolonged seizures in the immature brain. The lack of HSP72 and of late c-Fos expression likely reflect the absence of neuronal damage in this model of PTZ-induced SE in the immature rat.
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PMID:Effects of pentylenetetrazol-induced status epilepticus on c-Fos and HSP72 immunoreactivity in the immature rat brain. 940 20

Classical screening tests (maximal electroshock, MES, and threshold pentylenetetrazol, PTZ) employ non-epileptic rodents and identify antiepileptic drugs (AEDs) with mechanisms of action associated with significant CNS side effects. Thus MES identifies drugs acting on Na+ channels that produce cerebellar toxicity. It may be possible to produce novel AEDs more selectively targeted at voltage-sensitive (VS) ion channels. There is little specific evidence for the likely success of this strategy with subunit selective agents targeted at the different VS Na+ channels. Drugs targeted at specific VS Ca++ channels (T, N, P/Q types) may be useful in generalised seizures. There are many as yet unexplored possibilities relating to K+ channels. GABA related drugs acting on PTZ clonic seizures tend to induce sedation and muscle hypotonia. Studies in mice, particularly with knock-in mutations, but also with subunit selective agents acting via the GABA(A) benzodiazepine site, suggest that it is possible to produce agents which do or do not induce particular side effects (sedative, hypnotic, anxiolytic, muscle relaxant, amnesia, anaesthesia). Whether these findings transfer to man has yet to be established. Acquired epilepsy in rodents (e.g. kindling or spontaneous seizures following chemically- or electrically-induced status epilepticus) or acquired epilepsy in man (following prolonged febrile seizures or traumatic brain injury) is associated with multiple changes in the function and subunit composition of ion channels and receptor molecules. Optimal screening of novel AEDs, both for efficacy and side effects, requires models with receptor and ion channel changes similar to those in the target human syndrome.
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PMID:Do preclinical seizure models preselect certain adverse effects of antiepileptic drugs. 1215 Nov 15

Status epilepticus (SE) can cause spatial learning, memory, and behavioral deficits; however, little information is available, especially regarding the effects of such seizures on emotional memory and learning functions. We investigated the effects of SE on emotional memory, learning, and behavior in mature rats over short and long periods. SE was induced in 50- to 60-day-old rats (P50-P60) using intraperitoneal injections of pentylenetetrazole (PTZ, n = 20); control rats received saline (n = 10). All animals were tested with elevated T-maze and open-field tests on the 1st, 7th, 14th, and 180th days after SE to evaluate emotional memory, learning, and behavior. The number of fecal boli increased, and one-way escape latency was long in a short period after SE. PTZ-induced SE causes transient memory deficits, which is related to unconditioned fear, but it did not cause any persistent abnormalities of behavior, emotional memory, and learning in mature rats.
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PMID:The effects of pentylenetetrazole-induced status epilepticus on behavior, emotional memory, and learning in rats. 1514 9

The effects of two serotonergic (5-HT1A) receptor agonists (8-OH-DPAT; 0.01, 0.1, 0.3, 1 mg/kg, s.c., and Indorenate; 1, 3, 10 mg/kg, i.p.) were evaluated in three type of seizures in male Wistar rats: clonic-tonic convulsions induced by pentylenetetrazol (PTZ, 60 mg/kg, i.p.), status epilepticus (SE) of limbic seizures produced by kainic acid (KA, 10 mg/kg, i.p.) and tonic-clonic seizures by amygdala kindling. 8-OH-DPAT decreased the incidence of tonic seizures and the mortality rate induced by PTZ. Indorenate increased the latency to the PTZ-induced seizures and decreased the percentage of rats showing tonic extension and death. Concerning KA, 8-OH-DPAT augmented the latency and reduced the frequency of wet-dog shake (WDS) and generalized seizure (GS). At high doses it diminished the occurrence and delayed the establishment of SE. Indorenate augmented the latency to WDS, GS and SE, and diminished the number of GS. 8-OH-DPAT and Indorenate did not alter the expression of kindled seizures. However, Indorenate enhanced the refractoriness to subsequent seizures during the postictal depression. Some effects induced by 8-OH-DPAT and Indorenate on seizures evaluated and postictal depression were fully or partially blocked by WAY100635. These results suggest that 5-HT1A receptor agonists modify epileptic activity depending on the type of seizure.
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PMID:5-HT1A receptor agonists modify epileptic seizures in three experimental models in rats. 1599 34

This study focused on the evaluation of anticonvulsant properties of isonicotinic acid benzylamide (iso-Nic-BZA) in numerous experimental seizure models (maximal electroshock [MES]-, bicuculline [BIC]-, pentylenetetrazole [PTZ]-, pilocarpine [PILO]-, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA]-, kainic acid [KA]- and N-methyl-d-aspartic acid [NMDA]-induced seizures). Moreover, acute adverse-effect profile of the agent with respect to impairment of motor coordination was assessed in animals subjected to the chimney test. The evaluation of time-course and dose-response relationships for iso-Nic-BZA provided evidence that the compound produced the peak to maximum antielectroshock action and acute adverse effects at 5min after its systemic (i.p.) administration. Iso-Nic-BZA exerted a clear-cut anticonvulsant action against maximal electroshock-induced seizures in mice and its ED(50) value was 70.6 (56.4-88.4)mg/kg. The assessment of acute adverse effects in the chimney test revealed that the agent produced acute neurotoxic effects and its TD(50) value was 135.6 (108.8-169.0)mg/kg. Additionally, iso-Nic-BZA showed the anticonvulsant activity in numerous chemically-induced seizures (AMPA-, BIC-, KA-, and PTZ-evoked clonic convulsions), remaining virtually ineffective (at doses up to 200mg/kg) in PILO- and NMDA-induced seizures in mice. Based on this study, one can conclude that iso-Nic-BZA due to the short time to peak of its maximum anticonvulsant effects (5min after its i.p. administration), deserves more attention as a potential antiepileptic drug for patients in status epilepticus.
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PMID:Characterization of the anticonvulsant profile of isonicotinic acid benzylamide in various experimental seizure models in mice. 1754 62

Recently, we described the design and synthesis of azolylchroman derivatives as conformationally constrained analogs of (arylalkyl)azole anticonvulsants. In the present study, two distinct pharmacological models, lithium-pilocarpine induced seizure and PTZ-induced kindling were used to investigate both anticonvulsive and antiepileptogenic properties of the selected azolylchromanones including 7-chloro-3-(1H-imidazol-1-yl)chroman-4-one (I), 3-(1H-1,2,4-triazol-1-yl)chroman-4-one (II), trans-3-(1H-imidazol-1-yl)-2-methylchroman-4-one (III) and trans-7-chloro-3-(1H-imidazol-1-yl)-2-methylchroman-4-one (IV). Although compounds I and II were highly effective at the dose of 5 mg/kg against acute PTZ-induced convulsions as previously reported by us, these compounds exhibited limited effects in PTZ-induced kindling model. However, compound I was found to exert respectable action in delaying seizures and reducing seizure index at the dose of 10 mg/kg. In contrast, all tested compounds showed an anticonvulsant effect due to the considerably delayed onset of seizures in lithium-pilocarpine model. Compound I exhibited more effective action in delaying seizures as well as decreasing seizure duration in this model of epilepsy. In conclusion, the azolylchromanones I-IV, especially 7-chloro-3-(1H-imidazol-1-yl)chroman-4-one (I), were effective against lithium-pilocarpine induced status epilepticus, suggesting the potential application of the test compounds in the treatment of status epilepticus.
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PMID:Anticonvulsant and antiepileptogenic effects of azolylchromanones on lithium-pilocarpine induced seizures and pentylenetetrazole-kindling model of epilepsy. 1822 59


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