Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Central nervous system (CNS) reactions to intermittently infused lidocaine HCl (i.v.) were evaluated from cardiorespiratory and behavioral responses in 33 mongrel dogs. Threshold convulsive doses were established for each of three distinct and predictable seizure patterns. The first seizure activity observed was tonic extension (TE) which occurred at an infused lidocaine dose of 12.2+/-0.6 mg/kg followed by running activity after 22.7+/-0.9 mg/kg lidocaine was given. The threshold for intermittent tonic-clonic seizures (ICS) occurred at an infused lidocaine dose of 33.3+/-1.5 mg/kg. Mean blood pressure and pulse pressure increased at the onset of TE and ICS, with a decline in arterial pH and PCO2 during the ICS. No relationship was found between the animals' acid-base status and the ICS threshold. Toxicity to lidocaine in the dog is expressed by distinct behavioral responses suggesting lidocaine may affect various parts of the CNS. The mongrel dog appears to be a satisfactory and simple model system to evaluate lidocaine toxicity from behavioral and cardiorespiratory responses.
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PMID:Cardiorespiratory and behavioral reactions to the lidocaine-induced convulsions in the dog. 1 21

Procaine HCl and diphenylhydantoin (DPH) increased the duration and propagation of epileptiform afterdischarges (ADs) produced by electrical stimulation of the amygdala in rats. Procaine and DPH also increased the rate of seizure development (kindling) produced by repeated stimulation of the amygdala. Procaine and to a limited extentDPH would themselves act as convulsants in well kindled subjects. Diazepam, on the other hand, retarded or blocked amygdaloid kindling. Diazepam trigered a high frequency (20-30 c/sec) rhtthm in the amygdala, hippocampus and preoptic area. None of these drugs had any significant effect on potentials evoked in secondary limbic sites by single electrical pulses applied to the amygdala. Also, none of these drugs had any effect on recruiting or post-tetanic potentiation (PTP) in secondary sites produced by amygdala stimulation and none of the drugs had any effect on amygdaloid AD thresholds. The effects of these drugs on the responses evoked by anterior neocortex stimulation were quite different. Diazepam had no effect on any of the characteristics of the discharge or convulsion even at twice the dose levels used for the amygdala group. Procaine and DPH, however, blocked not only the eonvulsion but the AD as well. Eighty percent of the procaine- and DPH-treated rats failed to respond with neocortical AD even at current levels as high as 2000 muA. The few cortically stimulated subjects that did respond with an AD showed a subcortical rather than a neocortical seizure response. DPH had no effect on recruiting or PTP of the transcallosal response. Both procaine and DPH produced a weak but significant increase in the amplitude of the transcallosal evoked potential, while diazepam produce a weak decrement in that response.
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PMID:Effects of procaine hydrochloride, diazepam, and diphenylhydantoin on seizure development in cortical and subcortical structures in rats. 4 16

Intravenous procaine HCl given at low doses (0.5-2.5 mg/kg) to two monkeys with bilateral alumina hippocampal foci depressed interictal spiking or had little effect. At 5.0 mg/kg unilateral limbic activation occurred. At 10.0 mg/kg unilateral or bilateral limbic activation and generalized seizures could be evoked within 3-10 min. At higher doses (15 and 20 mg/kg) bilateral limbic activation or brief (one min) generalized seizures occurred. The unilateral-onset psychomotor seizures were not identical to spontaneous psychomotor seizures, and the generalized seizures never occurred spontaneously in these monkeys. However, these results do indicate that procaine challenges may selectively activate limbic epileptogenic areas without activation of debilitating generalized tonic-clonic seizures.
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PMID:Procaine-induced seizures in epileptic monkeys with bilateral hippocampal foci. 9 2

Most street hallucinogens contain either LSD or phenycyclidine HCl (PCP). Because the acute phase of LSD and PCP mimic several other drugs and conditions, it is important to exclude these other possibilities. When faced with LSD or PCP, "talking down" usually suffices for the mild case; management becomes more complex should hyperpyrexia, coma, seizures or a hypertensive crisis ensue. Diazepam, not a phenothiazine, is preferred for sedation.
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PMID:Management of hallucinogen abuse. 106 15

Male Sprague-Dawley rats when administered sc a sublethal dose of organophosphorus cholinesterase inhibitors such as the nerve agents, soman (100 micrograms/kg, sc), sarin (110 micrograms/kg, sc), tabun (200 micrograms/kg, sc), or VX (12 micrograms/kg, sc), developed seizures and severe muscle fasciculations within 15-20 min, lasting for 4-6 hr. Marked inhibition of acetylcholinesterase (AChE) and necrotic lesions in skeletal muscles such as soleus, extensor digitorum longus, and diaphragm were evident between 1-24 hr following injection. Pretreatment with memantine HCl (MEM, 18 mg/kg, sc) together with atropine sulfate (ATS, 16 mg/kg, sc), 60 min and 15 min, respectively, prior to nerve agents attenuated AChE inhibition, prevented myonecrosis, and muscle fasciculations as well as other signs of cholinergic toxicity. Pretreatment combining d-tubocurarine (d-TC, 0.075 mg/kg, sc) and ATS (16 mg/kg, sc) prevented the myonecrosis and fasciculation without protecting AChE against inhibition by these nerve agents. Neither MEM, d-TC, nor ATS in the concentration given interfered with the normal behavior of the rats. The role of d-TC and ATS interaction with presynaptic receptors regulating ACh release and MEM's role in modulating neural hyperactivity as protective mechanisms are discussed.
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PMID:Potential of memantine, D-tubocurarine, and atropine in preventing acute toxic myopathy induced by organophosphate nerve agents: soman, sarin, tabun and VX. 147 66

In situ hybridization for c-fos mRNA was performed on brain sections (a) from rats after an acute cocaine-induced seizure or from saline-injected controls and (b) from rats after their first cocaine-kindled seizure, as well as from rats that had not yet developed cocaine-kindled seizures (but were exposed to the same amount of cocaine as those that did exhibit convulsions) and from saline-injected controls. Increased expression of c-fos mRNA was observed in animals demonstrating cocaine-induced seizures acutely or following pharmacological kindling. Rats that experienced acute seizures after cocaine (65 mg/kg) showed pronounced increase in expression of c-fos mRNA in the dentate gyrus of the hippocampus and olfactory bulb. Increases were also observed in several other limbic cortical regions, as well as the striatum and ventromedial hypothalamic nucleus (VMH). In rats that were injected daily with an initially subconvulsive dose of cocaine-HCl (40 mg/kg), the cocaine-kindled seizures induced elevations in c-fos mRNA in the same brain regions as with an acute cocaine-induced seizure with the single exception of the VMH. These findings not only suggest the involvement of limbic, cortical and striatal structures in the cocaine-induced seizure, but also raise the possibility that alterations in the proto-oncogene c-fos and its subsequent impact on gene expression could play a role in the changes in neural excitability associated with cocaine-induced kindling.
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PMID:Expression of c-fos mRNA in acute and kindled cocaine seizures in rats. 149 73

Flumazenil is a new drug indicated for the reversal of the sedative effects of benzodiazepines mediated at the benzodiazepine-receptor site. Worldwide sources to date have disclosed 43 cases of seizures related, at least temporally, to the intravenous administration of flumazenil. There was no apparent relationship between the dose of flumazenil and the development of seizures, which occurred at doses ranging from 0.2 to 10.0 mg. The seizures were not considered to be a toxic effect of flumazenil, but many of them probably were due to an unmasking of the anticonvulsant effect of the previously used benzodiazepine or to a severe benzodiazepine-withdrawal syndrome. Eighteen (42%) of the patients had ingested overdoses of cyclic antidepressants, which were considered responsible for the seizures. In addition to patients with concurrent cyclic antidepressant poisoning, high-risk populations include patients who have been treated with benzodiazepines for a seizure disorder or an acute convulsive episode, patients with concurrent major sedative-hypnotic drug withdrawal, patients who have recently been treated with repeated doses of parenteral benzodiazepines, and overdose patients with myoclonic jerking or seizure activity before flumazenil administration. To minimize the likelihood of a seizure, it is recommended that flumazenil not be administered to patients who have used benzodiazepines for the treatment of seizure disorders or to patients who have ingested drugs (eg, cyclic antidepressants, cocaine, lithium, methylxanthines, isoniazid, propoxyphene, monoamine oxidase inhibitors, buproprion HCl, and cyclosporine) that place them at risk for the development of seizures.
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PMID:Flumazenil and seizures: analysis of 43 cases. 161 50

The involvement of excitatory amino acid (EAA) receptors in mediation of the toxic effects of cocaine was studied in male ICR mice. Cocaine HCl (90 mg/kg, IP) induced seizures in 95% and death within 24 h in 68% (n = 135) of the animals. There was a significant correlation (r = .54) between the time to onset of convulsions and the time to death in mice which died within 30 min of injection (n = 84). Pretreatment with selected EAA receptor antagonists 15 min prior to cocaine differentially blocked cocaine toxicity. Selective N-methyl-D-aspartic acid (NMDA) receptor antagonists (MK-801, dextrorphan, CPP) decreased both the incidence of seizures and mortality. A nonselective EAA antagonist, kynurenic acid, decreased lethality in doses which did not reduce convulsions. A similar action was observed following pretreatment with the selective kainic acid/AMPA receptor antagonist, GDEE. Antagonists at EAA receptors can provide significant protection against cocaine-induced toxicity. Moreover, the data provide evidence for the involvement of both NMDA and non-NMDA receptor subtypes in aspects of cocaine toxicity.
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PMID:Glutamate receptor antagonists block cocaine-induced convulsions and death. 168 27

The effect of i.p. or i.v. administration of the non-N-methyl-D-aspartate antagonists, GYKI 52466 (1-(4-aminophenyl)-4-methyl-7,8-methylendioxy-5H-2,3-benzodiazepin e.HCl, molecular weight 330) and NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)-quinoxaline, molecular weight 342) on sound-induced seizures in rats and photically induced myoclonus in baboons was studied. In both species an anticonvulsant effect occurred 15-60 min after administration of GYKI 52466 or NBQX. The ED50 value for clonic seizure suppression for GYKI 52466 at 30 min was 39 (rats, i.p.) and at 15 min was 13 (Papio papio, i.v.) mumol kg-1 and for NBQX at 30 min was 40 (rats, i.p.) and at 15 min approximately 10 (Papio papio, i.v.) mumol kg-1. Side effects were not observed in rats; apparent side effects in baboons probably arose from drug formulation. The anticonvulsant actions of GYKI 52466 and NBQX suggest a possible role for non-NMDA antagonists in the therapy of epilepsy.
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PMID:The non-N-methyl-D-aspartate receptor antagonists, GYKI 52466 and NBQX are anticonvulsant in two animal models of reflex epilepsy. 168 56

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


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