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)

This investigation was carried out to test the hypothesis that amygdaloid epileptiform activity is due to cholinergic hyperactivity. It was designed to study the underlying physiopathology of, and to act as an experimental model for, psychomotor epilepsy. Neostigmine was injected intracerebrally into the amygdala of the cebus monkey with chronically implanted "chemitrodes" fitted with EEG recording electrodes. The injections were made in the basal amygdaloid nucleus which normally shows very high acetylcholinesterase (AChE) enzymatic activity in histochemical preparations. Neostigmine injection resulted in very high amplitude spike activity in the amygdala only. Other brain areas, including the neighboring temporal cortex, did not show any marked EEG changes. In the first day or two, these EEG changes were associated with myoclonus localized in the ipsilateral muscles of facial expression and also associated with masticatory seizures. Subsequently the animal became aggressive and remained so several months after the injection of neostigmine. The EEG changes continued for approximately 6 weeks. Intramuscular injections of atropine diminished the amplitude of the epileptiform EEG discharges and modified slightly the animal's behavior.
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PMID:Neostigmine activated epileptiform discharge in the amygdala: electrographic-behavioral correlations. 10 9

The enzymes of the cholinergic system have been investigated in discrete brain areas in alcohol-dependent rats, which were still intoxicated or were undergoing withdrawal. The ethanol intoxication resulted in a slight, but significant increase in choline acetyltransferase (CAT) activity in the caudate nucleus both 1 and 7 h after the last dose of ethanol. We also found a significant decrease in CAT activity in the temporal limbic cortex while rats were highly intoxicated. All other brain regions investigated, e.g., cerebellum, pons-medulla, frontoparietal cortex, hypothalamus and septum showed unchanged CAT activity. Rats were also analysed immediately following the onset of a withdrawal-induced audiogenic convulsive seizure where, in addition to the striatum, depressed CAT activity was observed in the hippocampus. In all the analysed situations acetylcholinesterase activity remained unchanged. These results show that ethanol intoxication leads to a perturbation in the synthetic capacity of acetylcholine in certain defined brain structures and that this may have some correlation to the observed behavioural impairments.
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PMID:Cholinergic involvement in ethanol intoxication and withdrawal-induced seizure susceptibility. 10 88

The activity of ATP-ase and acetylcholinesterase (AChE) in crude mitochondrial fraction (CMF) and microsomal fraction of rat brain cortex and the spinal cord was studied in clonic seizures evoked by electroshock and 5 min after them. Inhibition of the Na, K-ATP-ase activity of the CMF of the brain at the clonic phase of convulsions and an increase in the activity of this enzyme in all the fractions of the tissues under study at the postconvulsive period were revealed. The activity of Ca-ATP-ase in the CMF of the brain increased during the convulsions and decreased at the postconfulsive period. The activity of Mg-ATP-ase remained unchanged. The AChE activity, as a rule increased during the convulsions, and grew even more during the postconvulsive period; the spinal cord tissue displayed a reduction of the activation effect. A possibility of structural reconstructions in the excitable neuron membranes during the convulsive activity is discussed.
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PMID:[Na, K-ATP-ase and acetylcholinesterase activity of the membrane structures of the rat brain and spinal cord during the seizure process]. 13 79

When the insecticide parathion was administered to awake, unrestrained rats with chronically implanted brain electrodes, it was observed that the latency of the averaged flash-evoked potential in the visual cortex and superior colliculus was increased and the amplitude was decreased 2 to 4 hours later with responses returning to pretreatment levels about 8 hours after administration. Similarly, after administration of several dose levels of parathion in the rat, durations of phases of the maximal electroshock seizure (MES) pattern were altered to the greatest extent 4 hours later, but effects disappeared at 24 hours. These effects of parathion on the MES and evoked potentials coincided with a fall in blood and brain acetylcholinesterase (AChe) activities but disappeared after AChe inhibition had reached its peak and stabilized. Brain AChe activities required 2 to 4 weeks for recovery whereas blood AChe activity recovered in 1 week following inhibition by parathion (at least 2 mg/kg body weight). Studies in the monkey demonstrated similar results. Because these measurements of central nervous system function returned to normal despite continued inhibition of AChe activity, the results are interpreted to mean either that adaptation of evoked potentials or MES responses to prolonged AChe inhibition can occur in the rat and monkey after parathion administration or that some of the effects of parathion do not depend on AChe inhibition. Administration of DDT (100 mg/kg by mouth) to awake, unrestrained rats markedly increased the amplitude of spontaneous electrical activity in the cerebellum, whereas there was much less effect on electrical activity recorded simultaneously in the occipital cortex, reticular formation, and medial geniculate body. Similarly, DDT administration had marked effects on the averaged, sound evoked potential recorded in the cerebellum; DDT caused the appearance and increased the amplitude of an early component of this response not usually present during control recordings. Sound-evoked potentials recorded simultaneously from the frontal and occipital cortex and reticular formation were affected less or were decreased in amplitude by administration of DDT.
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PMID:Some aspects of neurophysiological basis of insecticide action. 18 31

The activity of acetylcholinesterase and butyrilcholinesterase was studied during prolonged seizures developing from a primary-cortical focus. The activity was found to spread both along the wide limbic system, which indicates to participation of cholinergic agents in processes of "recurrent generalization" of excitations, and along the horizontal system of fibers connecting both hemispheres. This latter finding indicates to participation of cholinergic mediatory mechanisms in formation of seizures.
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PMID:[Cerebral cholinesterase under conditions of a generalized convulsive seizure]. 102 30

The effects of tacrine (5 mg/kg i.p.), a potent acetylcholinesterase inhibitor, were studied in rats pretreated (24 h beforehand) with a single dose (12 mEq/kg i.p.) of LiCl. Tacrine and LiCl were ineffective when given individually. Tacrine elicited seizures and brain damage in 90% of the rats treated. The intracerebroventricular microinfusion of N omega-nitro-L-arginine methyl ester (300 micrograms given 24 h after LiCl administration) significantly reduced the seizures and brain damage produced by tacrine (given 15 min later). These experiments suggest that the seizures and brain damage elicited by tacrine may be due, in part, to increased nitric oxide production in the brain.
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PMID:Tacrine-induced seizures and brain damage in LiCl-treated rats can be prevented by N omega-nitro-L-arginine methyl ester. 132 16

The changes in extracellular acetylcholine and glutamate levels were determined, during the course of seizures induced by soman, an irreversible inhibitor of acetylcholinesterase, in the CA1 hippocampal area of rats previously injected with atropine or normal saline into septum. The marked increases observed in soman-treated animals were abolished in rats receiving atropine. These data strongly suggest that, during soman intoxication, septal cholinoceptive cells play a key role in controlling the release of acetylcholine and glutamate in hippocampus. The mechanisms underlying this phenomenon are discussed.
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PMID:Changes in hippocampal acetylcholine and glutamate extracellular levels during soman-induced seizures: influence of septal cholinoceptive cells. 135

Recent studies in this laboratory have demonstrated that intramuscular injection of the irreversible acetylcholinesterase (AChE) inhibitor, soman (pinacolylmethylphosphonofluoridate), produces a rapid (1-2 h) and profound depletion (70% of control) of norepinephrine (NE) in the olfactory bulb and forebrain. NE is decreased only in convulsing animals. As NE-containing locus coeruleus (LC) neurons provide the only NE input to the olfactory bulb and the major NE innervation of the forebrain, the reduction of NE suggests that soman may cause tonic activation of LC neurons leading to rapid depletion of NE. Activation of LC may result from: (i) facilitation of cholinergic transmission in LC; (ii) soman-induced activation of excitatory inputs to LC; or (iii) generalized activation of LC neurons due to seizures. The present experiments were designed to assess these alternatives. We examined whether LC neuronal activity, c-fos expression, and AChE staining are altered after peripheral (systemic) or direct intracoerulear injection of soman in anesthetized rats. Both modes of soman administration rapidly and potently increase the spontaneous discharge rate of LC neurons. This activation was associated with a desynchronization of the electroencephalogram, but not with seizures. The discharge of LC neurons remained elevated at all postsoman intervals examined (up to 2 h) and was rapidly and completely reversed by systemic injection of the muscarinic receptor antagonist scopolamine hydrochloride, but not by the nicotinic receptor antagonist mecamylamine. Both systemic and intracoerulear soman administration completely inhibited AChE staining in LC and rapidly induced the expression of c-fos in LC neurons. These results demonstrate that soman potently and tonically activates LC neurons. This effect appears to be mediated by direct inhibition of AChE in LC leading to a rapid accumulation of ACh. Unhydrolyzed ACh tonically activates LC neurons via muscarinic receptors. Soman-induced activation of LC neurons does not require seizures. We conclude that depletion of forebrain and olfactory bulb NE after systemic administration of soman results from tonic hypercholinergic stimulation of LC.
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PMID:Tonic activation of locus coeruleus neurons by systemic or intracoerulear microinjection of an irreversible acetylcholinesterase inhibitor: increased discharge rate and induction of C-fos. 138 4

This paper reviews chemical models of epilepsy and their relevance in the identification and characterization of anticonvulsants. For each convulsant we discuss possible modes of administration, clinical type(s) of seizures induced, proposed mechanism(s) of epileptogenesis and, where available, responsiveness of the induced seizures to anticonvulsants. The following compounds are reviewed: pentylenetetrazol, bicuculline, penicillin, picrotoxin, beta-carbolines, 3-mercaptopropionic acid, hydrazides, allylglycine; the glycine antagonist strychnine; gamma-hydroxybutyrate; excitatory amino acids (glutamate, aspartate, N-methyl-D-aspartate, quisqualate, kainate, quinolinic acid); monosubstituted guanidino compounds, metals (alumina, cobalt, zinc, iron); neuropeptides (opioid peptides, corticotropin releasing factor, somatostatin, vasopressin); cholinergic agents (acetylcholine, acetylcholinesterase inhibitors, pilocarpine); tetanus toxin; flurothyl; folates; homocysteine and colchicine. Although there are a multitude of chemical models of epilepsy, only a limited number are applied in the routine screening of potential anticonvulsants. Some chemical models have a predictive value with regard to the clinical profile of efficacy of the tested anticonvulsants. Some chemical models may contribute to a better understanding of possible mechanisms of epileptogenesis.
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PMID:Chemical models of epilepsy with some reference to their applicability in the development of anticonvulsants. 139 44

The organophosphate chemical nerve agent, soman, causes convulsions, neuropathology, and, ultimately, death. A major problem in treating soman intoxication is that peripherally acting pharmacological agents which prevent death do not prevent seizures. Although a primary cause of these symptoms is the excess of acetylcholine which follows acetylcholinesterase (AChE) inhibition, centrally acting muscarinic blockers, such as atropine, alleviate, but do not block, the convulsive actions of soman. Moreover, there is a relatively weak relationship between CNS reductions of AChE and the incidence of convulsions. There is evidence suggesting that soman intoxication stimulates the release of norepinephrine (NE) in the brain. Recent evidence has implicated NE in the induction and/or maintenance of seizures. Thus, in the present study the relations among soman-induced convulsions, AChE inhibition, and brain NE and other monoamine changes were examined. The time course of brain NE recovery was also determined. Rats were injected (im) with a single dose (78 micrograms/kg) of soman. At this dose 68% of the injected rats developed convulsions. Both convulsive and nonconvulsive rats were sacrificed between 1 and 96 h following soman injection and NE levels in the rostral forebrain and olfactory bulb were determined by HPLC with electrochemical detection. In all convulsive rats NE levels declined substantially. Forebrain NE levels were decreased by 50% at 1 h and 70% at 2 h following soman injection. Recovery of NE began at 8 h and was complete by 96 h following soman administration. Although nonconvulsive rats showed other signs of intoxication, NE levels in these rats were unchanged. Dopamine (DA) and serotonin (5-HT) levels were not significantly affected in either convulsive or nonconvulsive rats. However, 5-hydroxyindoleacetic acid, the major metabolite of 5-HT, and homovanillic acid and 3,4-dihydroxyphenylacetic acid, the two major metabolites of DA, were increased significantly in the forebrain of convulsive, but not nonconvulsive rats, indicating an increase in 5-HT and DA turnover. However, in contrast to the abrupt decline in NE, these increases in DA and 5-HT metabolites were slow and progressive. Taken together, the present results and other recent findings suggest that rapid, sustained NE release could play a role in the induction and/or maintenance of soman-induced convulsions, whereas increased release of 5-HT and DA may be a consequence of seizures. Further investigation of the role of NE in soman-induced convulsions may lead to improved treatment of soman intoxication and a better understanding of the role of NE in other forms of seizures, including human epilepsy.
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PMID:Brain norepinephrine reductions in soman-intoxicated rats: association with convulsions and AChE inhibition, time course, and relation to other monoamines. 142 25


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