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

In mice chronically treated with ethanol (in a liquid diet containing 6% ethanol ad libitum for 2 weeks), brain tryptophan hydroxylase (TPH) activity was increased (by 30-45% in whole brain), while brain tyrosine hydroxylase activity remained unchanged. Such chronic ethanol treatment also induced susceptibility to audiogenic seizures during withdrawal (60% incidence). When ethanol treatment was given to adrenalectomized (Adx) mice, the increase of brain TPH activity and the development of withdrawal audiogenic seizures were both prevented. In Adx mice receiving daily injections of corticosterone (0.5 mg/mouse), the ethanol-induced increase of brain TPH activity and the occurrence of withdrawal audiogenic seizures were both restored. Similarly, the ethanol-induced increase of liver alcohol dehydrogenase activity (by 60%) was prevented in Adx mice and restored by corticosterone replacement. It was noted that in all three cases replacement with such large doses of the corticoid did not enhance the ethanol effects, but merely restored the effects to the levels observed in intact mice. Apparently, glucocorticoids are required in a permissive role in order for the ethanol effects to occur.
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PMID:The permissive role of glucocorticoids in the development of ethanol dependence and tolerance. 2 Oct 65

L-proline induces retroactive amnesia without causing brain seizures or isoelectric activity. 3,4-dehydro-DL-proline, a proline analog containing a double-bond in the 5-membered ring, has similar effects at a smaller dose. Three experiments describe the amnestic qualities of 3,4-dehydro-DL-proline in a chick memory paradigm, the retrograde quality of this amnesia, and its existence in a mammalian (mouse) preparation. Finally, EEG records show that chicks injected with amnestic doses of 3,4-dehydro-DL-proline do not exhibit seizure spiking or abnormal electrical activity.
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PMID:Retrograde amnesia in chicks and mice induced by 3,4-dehydro-DL-proline, a proline analog. 57 97

Each of six kynurenines tested (DL-kynurenine, quinolinic, 3-hydroxy-anthranilic, xanthurenic, picolinic, and nicotinic acids) injected into brain ventricles in mice in doses of 25--60 mcg produced motor excitement and/or clonic convulsions. Anthranilic acid did not produce these effects. The strongest metabolite was quinolinic acid, which was active in a dose of 1 mcg. It was also the only compound which produced motor excitement and convulsions after intraperitoneal injection (in doses of 400--600 mg/kg, i.e. 10,000--15,000 mcg per mouse). The hypothermic effect of intraventricularly-injected kynurenines was roughly similar to that of intraperitoneally-injected material at 100--1000 times higher doses. These data suggest poor penetration of kynurenines formed in the liver into the brain, and the possible involvement of these metabolites of tryptophan (particularly if they are formed inside the brain) in the mechanism of seizures.
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PMID:Stimulant and convulsive effects of kynurenines injected into brain ventricles in mice. 64 43

The effects of AT II alone and in combinations with the anticonvulsants diazepam, clonazepam and di-n-propylacetate (depakine) on PTZ-kindling in mice were studied. PTZ-kindling was provoked by intraperitoneal (i.p.) injections of PTZ (40 mg/kg) every other day in male albino mice until clonic seizures appeared. AT II in doses 0.1 and 1 microgram/mouse intracerebronventricularly (i.c.v.) decreased the intensity of seizures in PTZ-kindled mice. Diazepam (0.25 and 1 mg/kg i.p.), clonazepam (0.05 and 0.1 mg/kg i.p.) and depakine (75 mg/kg) inhibited PTZ-kindled seizures. Combinations of ineffective doses of AT II (0.05 microgram/mouse) and ineffective doses of diazepam (0.1 mg/kg) or clonazepam (0.01 mg/kg) or depakine (50 mg/kg) significantly decreased the intensity of seizures in PTZ-kindled mice. The seizure-decreasing effect of diazepam, clonazepam and depakine on PTZ-kindling in mice, which was potentiated by AT II, suggests interactions of AT II receptors with GABA and benzodiazepine receptors or with the GABA-benzodiazepine receptor-ionophore complex, probably effectuated through alsoteric mechanisms. A more efficient coupling of the GABA-benzodiazepine receptor-ionophore complex with AT II receptors might also be the reason for the decrease of the intensity of seizures in PTZ-kindled mice.
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PMID:Interactions between angiotensin II, diazepam, clonazepam and di-n-propylacetate in pentylenetetrazol kindling seizures in mice. 164 72

Male Sprague-Dawley rats injected sc with a single sublethal dose of the organophosphate nerve agent, soman (100 micrograms/kg), had motor limbic seizures within 5-15 min. Pretreatment with a single dose of memantine HCl (MEM, 18 mg/kg, sc), alone or in combination with atropine sulfate (ATS, 16 mg/kg, sc), before soman prevented seizures without sedation or ataxia. Rats appeared normal or demonstrated increased exploratory activity. Excessive salivation, a peripheral manifestation of soman intoxication, was decreased by ATS, but pretreatment with ATS alone did not prevent seizures. After seizure onset, MEM +/- ATS, but not ATS, abolished seizures. Acetylcholinesterase (AChE) activity in several brain regions (cortex, stem, striatum, and hippocampus) was markedly reduced by soman, but not by MEM, ATS, or MEM + ATS. Preadministration of MEM + ATS in vivo significantly protected AChE from inhibition by soman. Memantine reduced inhibition of AChE activity in crude brain homogenates by soman, but not by edrophonium (anionic site inhibitor) or decamethonium (peripheral site inhibitor). Thus, MEM may bind to a different modulatory site, not yet characterized, to protect AChE. When given after onset of soman-induced seizures, treatment with MEM +/- ATS did not reactivate AChE although seizures were controlled, suggesting additional anticonvulsant mechanisms of action. At concentrations (10(-4) to 5 x 10(-4) M) which did not significantly alter the spontaneous firing of action potentials (APs), MEM limited sustained high frequency repetitive firing (SRF) induced by depolarization of spinal cord (mouse and rat) and neocortical (mouse) neurons in monolayer-dissociated cell culture. In the same range of concentrations, ATS both limited SRF and suppressed spontaneous activity, suggesting toxicity. In addition, MEM and ATS reversibly produced use-dependent block of depolarizing responses to acetylcholine (ACh) applied by pressure ejection to spinal cord neurons. Thus, the anticonvulsant efficacy of MEM, with or without ATS, may have resulted from a combination of actions, including protection of AChE from inhibition by soman, limitation of high frequency firing of APs, and blockade of excitatory postsynaptic responses to ACh.
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PMID:Prophylactic and therapeutic efficacy of memantine against seizures produced by soman in the rat. 173 53

In order to determine the gamma-L-glutamyl-L-aspartate (gamma-LGLA) site of action in excitatory amino acids (EAA) systems, we studied the gamma-LGLA anticonvulsant activity against seizures induced in mice by pentylenetetrazol, picrotoxin and EAA agonists. The mice were protected against seizures induced by pentylenetetrazol (80 mg/kg s.c.) and picrotoxin (2.75 mg/kg s.c.) after intraperitoneal administration of gamma-LGLA with two significant peak effects around the doses of 0.25 and 200 mumol/kg as revealed by the dose-response curves obtained in both experiments. Use of an intracerebroventricular co-injection procedure showed that gamma-LGLA dose dependently suppressed the seizures induced by NMDA (1 nmol/mouse) with a maximal effect at 80 nmol/mouse but, at the same dose, it only slightly suppressed seizures induced by kainate (0.3 and 0.8 nmol/mouse) or by quisqualate (18.5 nmol/mouse). The anticonvulsant activity of gamma-LGLA on these chemically induced seizures is consistent with an antagonistic action of gamma-LGLA on NMDA receptor subtypes.
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PMID:NMDA antagonist properties of gamma-L-glutamyl-L-aspartate demonstrated on chemically induced seizures in mice. 214 37

The antagonist effect of (+/-)-3-amino-1-hydroxypyrrolid-2-one (HA-966) at the N-methyl-D-aspartate (NMDA) receptor occurs through a selective interaction with the glycine modulatory site within the receptor complex. When the enantiomers of (+/-)-HA-966 were resolved, the (R)-(+)-enantiomer was found to be a selective glycine/NMDA receptor antagonist, a property that accounts for its anticonvulsant activity in vivo. In contrast, the (S)-(-)-enantiomer was only weakly active as an NMDA-receptor antagonist, but nevertheless it possessed a marked sedative and muscle relaxant action in vivo. In radioligand binding experiments, (+)-HA-966 inhibited strychnine-insensitive [3H]glycine binding to rat cerebral cortex synaptic membranes with an IC50 of 12.5 microM, whereas (-)-HA-966 had an IC50 value of 339 microM. In electrophysiological experiments, (+)-HA-966 selectively antagonized NMDA receptor responses in rat cortical slices, whereas the (-)-enantiomer was much weaker. On cultured cortical neurones (+)-HA-966 inhibited glycine-potentiated NMDA responses with an IC50 = 13 microM compared with (-)-HA-966, which has an IC50 = 708 microM. In agreement with findings with racemic HA-966, even high concentrations of (+)-HA-966 did not completely inhibit NMDA responses, suggesting that (+)-HA-966 is a low-efficacy partial agonist. (+)-HA-966 produced parallel shifts to the right of the glycine concentration curve for potentiation of NMDA responses, resulting in an estimated pKb = 5.6. In mice, (+)-HA-966 antagonized sound and N-methyl-DL-aspartic acid (NMDLA)-induced seizures with ED50 values of 52.6 mg/kg of body weight (i.p.) and 900 mg/kg (i.v.), respectively. The coadministration of D-serine dose-dependently (10-100 micrograms into the cerebral ventricles per mouse) antagonized the anticonvulsant effect of a submaximal dose of (+)-HA-966 (100 micrograms administered directly into the cerebral ventricles) against NMDLA-induced seizures. The sedative/ataxic effect of racemic HA-966 was mainly attributable to the (-)-enantiomer, which was greater than 25-fold more potent than the (+)-enantiomer. It is suggested that, as in the case of the sedative gamma-butyrolactone, disruption of striatal dopaminergic mechanisms may be responsible for this action.
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PMID:Enantiomers of HA-966 (3-amino-1-hydroxypyrrolid-2-one) exhibit distinct central nervous system effects: (+)-HA-966 is a selective glycine/N-methyl-D-aspartate receptor antagonist, but (-)-HA-966 is a potent gamma-butyrolactone-like sedative. 215 94

The synthetic alpha-cyano-phenoxybenzyl-containing pyrethroid insecticides act on the CNS of vertebrates and show a species-selective toxicity in the order fish greater than amphibians much greater than mammals greater than birds. Concentrations of [14C]cis-cypermethrin in the brains of representative members of each of these classes of chordates were measured at toxic signs (an onset of hyperactivity followed by seizures and loss of balance/equilibrium) as an indicator of target organ sensitivity. The concentration of cis-cypermethrin in brain, associated with toxic signs, in micrograms per gram (mean +/- SE) as determined by high-performance liquid chromatography was 0.08 +/- 0.03 (frog), 0.23 +/- 0.05 (trout), 1.71 +/- 0.33 (mouse), and 3.94 +/- 0.88 (quail). Trout brain was equally sensitive to the cis and trans isomers of cypermethrin. In both mouse and quail, some 90% of the radioactivity in the brain was parent pyrethroid. Trout and frog, however, afforded only 56 and 32%, respectively, of the brain 14C as cypermethrin, with the remaining radioactivity in both extractable and nonextractable metabolites, including 4'-hydroxy-cis-cypermethrin, which is potentially neuroactive. Following oral administration, cis-cypermethrin was readily absorbed and metabolized by quail. Intestinal uptake was far less rapid in trout and mouse, with unchanged cypermethrin dispersed in secreted bile, being readily eliminated from the intestines of fish. The uptake and metabolism of cis-cypermethrin and the brain sensitivities of these animals to the pyrethroid account for the observed differences in acute toxicity.
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PMID:Comparative toxicity of cis-cypermethrin in rainbow trout, frog, mouse, and quail. 348 48

Genetic control of the mouse epilepsy of E1 mouse isolated from ddY strain was investigated by crossbreeding with C57BL/6 mouse. A concept of the dominance deviation was applied for the explanation of the epileptic seizure inheritance in the generations of P1, F1, F2, B1 (F1 X E1 mouse) and B2 (F1 X C57BL/6 mouse), in which initial rate increase of the seizure frequency, seizure-inducing rotation numbers and seizure formative period as a function of the population growth were undertaken to be phenotypic measures. It was conclusive that the mouse epilepsy is apparently under genetic control by at least single gene with the seizure activity influencing factor(s) or by plural genes. Those are partially recessive for the allele assumed in cross-hybridized C57BL/6 mouse. No relevance of the coat color genotype and sex determination to the seizure segregation was observed obviously. Possible existence of epileptic substance(s) responsible for the enhancement of the seizure activity is also discussed.
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PMID:Crossbreeding analysis of the mouse epilepsy. 372 16

Viloxazine HCl is evaluated as an anticonvulsant in a wide range of rodent seizure models and in the epileptic baboon (Papio papio). In the maximal electroshock test, the oral ED50 for abolition of tonic extension was 9 mg/kg-1 after 30-min pretreatment (mouse) rising to 30 mg/kg-1 after 60 min (mouse and rat). Comparable ED50 values were also found for protection against tonic extension in the mouse induced by the administration of the chemical convulsants metrazole or 3-mercaptopropionic acid. In DBA/2 mice the ED50 for abolition of tonic extension during sound-induced seizures was 6.8 mg/kg-1 IP (30-min pretreatment). Pharmacokinetic studies in the mouse showed peak plasma levels to occur 30 min following oral doses, with a mean half-life of 58 min. The anticonvulsant plasma concentration was within 0.5 -- 1 microgram/ml-1. In the baboon, significant protection against photomyoclonic responses is observed 1 -- 2h after viloxazine (2.6 mg/kg-1 IV), during which period the plasma concentration was again 0.5-1 microgram/ml-1. After administration of approximately ten-times this latter dose level, i.e. 24 mg/kg-1 IV, a syndrome characterised by an abnormal EEG and, in some instances, seizure activity was observed.
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PMID:Anticonvulsant and proconvulsant properties of viloxazine hydrochloride: pharmacological and pharmacokinetic studies in rodents and the epileptic baboon. 680 38


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