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)

Lithium aluminum hydride reduction of 1,4-dimethyl-3-pyrazolidinone yielded 1,4-dimethylpyrazolidine. The latter compound and 1-methylpyrazolidine reacted with aryl isocyanates to produce 1-methyl-2-phenylcarbamoylpyrazolidines. Several of these adducts displayed significant anticonvulsant activity in the maximal electroshock seizure and pentylenetetrazol seizure threshold tests.
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PMID:Synthesis of 1-methyl-2-phenylcarbamoylpyrazolidines as potential anticonvulsant agents. 70 7

Lithium has become a widely accepted treatment for manic-depressive psychosis. It is dramatically effective for many cases of mania and is useful in the prevention of manic and depressive episodes. Hyperaggressiveness and hypersexuality are frequent components of manic-depressive illness and abate under the influence of lithium. A brief review is presented of the behavioral and biochemical pharmacology of lithium. This documents the inhibitory role which lithium can play in several examples of animal aggressive behavior including pain-elicited aggression, mouse killing in rats, isolation-induced aggression in mice, p-chlorophenylalanine-induced aggression in rats, and hypothalamically induced aggression in cats. The use of lithium to control human aggressive behavior has resulted in controversial findings. In epileptic conditions, improvement has been reported in interseizure aggressivity, but other reports indicate the possibility of increased seizures. Improvement in aggressive behavior in childhood has occasionally been reported as well as in emotionally unstable character disorders in young female patients. Te was a single blind study and the other a large but uncontrolled study. Both studies reported an improvement in aggressiveness as indicated by fewer recorded reports (tickets) for fighting. The final study reported is a study of 12 male delinquents age 16 to 23. They received lithium or placebo for 4 months inside an institution and then a trial of lithium for 1 to 12 months on an outpatient basis. Analysis of results in terms of the number of aggressive antisocial acts showed fewer serious aggressive episodes when the lithium level was between 0.6 and 1 meq/liter than when it was between 0.0 and 0.6 meq/liter. These results must be viewed with caution and are only suggestive since the study was not double blind.
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PMID:Lithium in the treatment of aggression. 109 Jul 6

Lithium is known to potentiate the ability of pilocarpine to induce status epilepticus in rats. The goal of this study was to determine whether lithium could potentiate pilocarpine-induced seizures in developing animals. Behavioral, electroencephalographic (EEG), and histopathological changes induced by systemic administration of lithium (3 meq/kg) followed 20 h later by pilocarpine (3, 10, 30, 60 mg/kg) were studied in 3-30-day-old rats. Lithium followed by pilocarpine (30 and 60 mg/kg) induced hyperactivity, tremor, loss of postural control and scratching but no electrographic seizures in 3-8-day-old rats. In the 7-10-day-old animals pretreatment with lithium and pilocarpine 60 mg/kg induced status epilepticus with sustained myoclonus and continuous bilateral synchronous spike and sharp wave, but doses of pilocarpine lower than 60 mg/kg had no effect. The susceptibility to lithium-pilocarpine-induced status epilepticus increased markedly during the third postnatal week of life. During this time period, rats treated with lithium (3 meq/kg) plus pilocarpine 10 mg/kg exhibited behavioral and EEG manifestations of status epilepticus. The same combination of lithium and pilocarpine failed to induce status epilepticus either before or after the third week of life. Histopathological analysis of the brains of the animals used in these studies failed to demonstrate the widespread damage reported in adult rats that have undergone lithium-pilocarpine-induced status epilepticus.
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PMID:Ontogenic study of lithium-pilocarpine-induced status epilepticus in rats. 132 90

A randomized prospective trial has shown that folic acid started before conception and continued for the first trimester reduces the risk of recurrence of neural tube defects by 72% in women with a previously affected child. Carbamazepine exposure in utero is associated with a 1% risk of spina bifida. Long-term follow-up of antenatal exposure to phenobarbital and carbamazepine in two groups of infants shows no neurologic differences between the two groups. Magnesium sulfate is more effective in prevention of recurrent eclamptic seizures than phenytoin. During pregnancy, the need for thyroxine increases in many women. Vitamin B6 and ginger are both effective for nausea and vomiting in early pregnancy. Low-dose aspirin does not change the course of preeclampsia when it is started after the diagnosis is made. Angiotensin-converting enzyme inhibitors cause significant disturbances of fetal and neonatal renal function. Prophylactic beta-adrenergic agents fail to prevent prematurity in twins. Oral tocolysis with magnesium chloride or ritodrine is no more effective than observation alone. The risk of primary pulmonary hypertension in the newborn after indomethacin tocolysis is increased with prolonged therapy. Lithium causes polyhydramnios from fetal diabetes insipidus in utero. Treatment of Ureaplasma urealyticum infection with erythromycin during pregnancy does not eliminate the organism from the lower genital tract and does not improve perinatal outcome.
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PMID:Drug therapy during pregnancy. 154 29

Lithium pretreatment of rats has previously been shown to potentiate the convulsant effects of cholinomimetic drugs, such as pilocarpine. The first objective of this project was to determine if lithium also potentiates seizures induced by other classes of drugs. Lithium pretreatment of rats did not affect seizure activity induced by administration of N-methyl-D-aspartate, kainic acid, bicuculline, or pentylenetetrazole. This suggests that the proconvulsant effect of lithium is largely selective for cholinomimetics. A second series of experiments investigated possible mechanisms of the lithium potentiation of pilocarpine-induced seizures. The alpha 2-adrenergic receptor agonist clonidine suppressed seizure development, and the antagonist idazoxan enhanced the onset of seizures, suggesting that endogenous norepinephrine provides anticonvulsant properties. Administration of the norepinephrine depleter DSP-4 potentiated pilocarpine-induced seizures. These results suggest that the previously reported impairment of noradrenergic function by lithium may play a role in its potentiation of cholinomimetic-induced seizures.
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PMID:Analysis of the convulsant-potentiating effects of lithium in rats. 184 79

The heterogenous psychoses in epilepsies, caused by well known conditions, are not rare but associated with regularly a few of seizure-types not with the nature and development of attacks. Polar transitional ranks and converging courses of schizophrenic (accentuated) syndromes in epilepsies and idiopathic schizophrenias are rather frequent. Also (sub-)acute schizophrenic psychoses are corresponding to the complete palette of first and second rank symptoms (K. Schneider) of idiopathic schizophrenias. After manifestations of epilepsy these syndromes can appear at any time. It is given a profile of risks. Progressive avoidance of a. phenylaceturea, b. mixtures of antiepileptics did not put an end to psychotic syndromes: Long-term therapies with 1. Polytherapy, 2. Primidone and Phenytoin (dosedependant) as well as 3. Ethosuximide (-monotherapy) cause a disorder of feed back mechanisms, especially a disturbed regulation of vigilance and sleeping-waking-cycle and their psychological correlates. Carbamazepine and Sodium Valproate are, plasma-level-controlled of preventive antipsychotic effect. Selected neuroleptics of rather slight epileptogenic potency are of going down importance. Benzodiazepines are required mostly in prepsychotic syndromes, Lithium compounds in selected cases. There is no more alternative seizures or psychosis.
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PMID:[Psychoses in epilepsy]. 198 Oct 95

The mechanisms underlying the psychotropic actions of lithium are not established, but modulation of endogenous brain neurotransmitter systems is likely to be important. Several interactions of lithium with muscarinic responses have been reported, including a marked potentiation of seizures produced by muscarinic agonists. Because the mechanism by which lithium augments muscarinic seizures may be related to the mechanism by which it produces its psychotropic effects, we have studied the interaction of lithium and muscarinic agonists in vitro. Using rat hippocampal slices, we found that a muscarinic agonist, pilocarpine, increased postsynaptic neuronal excitability, but simultaneously decreased synaptic transmission because of presynaptic inhibition. Lithium did not alter pilocarpine's postsynaptic excitatory actions, but reversed its presynaptic inhibitory action, leading to markedly increased action potential firing. These presynaptic effects are not caused by alterations in presynaptic action potential shape or reliability of conduction, and do not involve pertussis toxin-sensitive G proteins. Activation of protein kinase C with phorbol-12,13-dibutyrate, or inhibition with H-7 and sphingosine, did not affect muscarinic presynaptic inhibition, but abolished lithium's ability to enhance synaptic transmission, suggesting that this effect of lithium involves protein kinase C. We propose that presynaptic facilitation accounts for lithium's potentiation of muscarinic seizures. Since these effects occur with concentrations of lithium used clinically, similar presynaptic effects in endogenous brain neurotransmitter systems may be important for lithium's psychotropic actions.
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PMID:Lithium enhances neuronal muscarinic excitation by presynaptic facilitation. 217 56

High-dose treatment with pilocarpine hydrochloride, a cholinergic muscarinic agonist, induces seizures in rodents following systemic or intracerebral administration. Pilocarpine seizures are characterized by a sequential development of behavioral patterns and electrographic activity. Hypoactivity, tremor, scratching, head bobbing, and myoclonic movements of the limbs progress to recurrent myoclonic convulsions with rearing, salivation, and falling, and status epilepticus. The sustained convulsions induced by pilocarpine are followed by widespread damage to the forebrain. The amygdala, thalamus, olfactory cortex, hippocampus, neocortex, and substantia nigra are the most sensitive regions to epilepsy-related damage following convulsions produced by pilocarpine. Spontaneous seizures are observed in the long-term period following the administration of convulsant doses of pilocarpine. Developmental studies show age-dependent differences in the response of rats to pilocarpine. Seizures are first noted in 7-12 day-old rats, and the adult pattern of behavioral and electroencephalographic sequelae of pilocarpine is seen in 15-21-day-old rats. During the third week of life the rats show an increased susceptibility to the convulsant action of pilocarpine relative to older and younger animals. The developmental progress of the convulsive response to pilocarpine does not correlate with evolution of the brain damage. The adult pattern of the damage is seen after a delay of 1-2 weeks in comparison with the evolution of seizures and status epilepticus. The susceptibility to seizures induced by pilocarpine increases in rats aged over 4 months. The basal ganglia curtail the generation and spread of seizures induced by pilocarpine. The caudate putamen, the substantia nigra, and the entopeduncular nucleus govern the propagation of pilocarpine-induced seizures. The antiepileptic drugs diazepam, clonazepam, phenobarbital, valproate, and trimethadione protect against pilocarpine-induced convulsions, while diphenylhydantoin and carbamazepine are ineffective. Ethosuximide and acetazolamide increase the susceptibility to convulsant action of pilocarpine. Lithium, morphine, and aminophylline also increase the susceptibility of rats to pilocarpine seizures. The pilocarpine seizure model may be of value in designing new therapeutic approaches to epilepsy.
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PMID:Review: cholinergic mechanisms and epileptogenesis. The seizures induced by pilocarpine: a novel experimental model of intractable epilepsy. 264 33

Electroencephalographic techniques were used to study generalized convulsive status epilepticus induced by administration of subconvulsive doses of cholinomimetics (e.g., pilocarpine) to rats pretreated with lithium chloride. Status epilepticus induced by this treatment was compared with status epilepticus induced by kainic acid. Lithium/pilocarpine-induced status epilepticus developed within 10 min of initial paroxysmal spike activity, 24 +/- 1 min (N = 20) after administration of pilocarpine, and continued uninterrupted for more than 3 h. Kainic acid (10 mg/kg)-induced status epilepticus developed approximately 60 min after initial spike activity, 96 +/- 3 min (N = 7) after kainate administration, and continued for 0.5 h. Thus, the interval of intermittent seizure activity and the duration of status epilepticus differed markedly between these two models. The potentiation by lithium (3 meq/kg) of the convulsant effect of cholinergic agonists was found to be 10 to 13-fold for two direct-acting cholinomimetics, pilocarpine and arecoline, whereas the convulsant effect of the indirect-acting agonist, physostigmine, was potentiated by 50%. The full proconvulsant effect of lithium lasted from 2 to 24 h after a single acute treatment (3 meq/kg). The dose response of the proconvulsant effect of lithium was determined and the EC50 of lithium was approximately 1.5 meq/kg when pilocarpine (30 mg/kg) was administered 20 h later. Chronic treatment with lithium for 4 weeks potentiated the convulsant effect of pilocarpine by more than 26-fold. These results demonstrated that both acute and chronic administration of lithium enhance cholinergic function in vivo. Potentiation of cholinergic function by lithium may play a role in the therapeutic action of lithium in affective disorders.
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PMID:Status epilepticus is produced by administration of cholinergic agonists to lithium-treated rats: comparison with kainic acid. 282 29

We assessed the acute effects of various drugs on amygdaloid kindled seizures induced with low-frequency stimulations. We used the number of stimulating pulses required for the induction of epileptic afterdischarge (pulse-number threshold; PNT) as an indicator of the seizure generating threshold and the duration of induced seizures (AD duration; ADD) as an indicator of the seizures. TRH increased the PNT without affecting the ADD at a high dose (1.2 mg/kg). Flunarizine decreased the PNT and ADD simultaneously at a high dose (50 mg/kg). Lithium increased the PNT without affecting the ADD at two doses (100 mg/kg, 200 mg/kg). Zotepine decreased the PNT without affecting the ADD at two doses (8 mg/kg, 16 mg/kg). We propose that the technique of low-frequency kindling is a useful experimental model in assessing the effects of antipsychotic or antiepileptic drugs on the excitability of the limbic regions.
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PMID:Acute effect of TRH, flunarizine, lithium and zotepine on amygdaloid kindled seizures induced with low-frequency stimulation. 289 77


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