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)

Lamotrigine is a new antiepileptic drug that may possess unique cognitive and behavioral characteristics. Although lamotrigine can produce neurobehavioral toxicity, it is generally well tolerated. In one study directly comparing lamotrigine to placebo as add-on therapy in patients with intractable epilepsy, no objective cognitive effects were observed in a limited neuropsychological battery. Several studies have demonstrated favorable effects of lamotrigine on psychological well-being that were not explained by simple effects on seizure frequency and severity. In direct comparisons with carbamazepine and phenytoin, lamotrigine has been reported to produce positive effects on quality of life scales of patient perception. In addition, positive behavioral effects have also been observed in two blinded studies and several open trials for patients with severe mental disability and refractory epilepsy. Future studies with more extensive neuropsychological assessments are needed to delineate the differential cognitive and behavioral effects of lamotrigine in epilepsy and psychiatric disorders.
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PMID:Behavioral and cognitive effects of lamotrigine. 942 30

Based on small numbers of patients, it is possible to make the following suggestions rather than categorical statements. For myoclonic seizures and epilepsies which are not otherwise specified, valproate seems of proven efficacy. Ethosuximide may be a useful adjunct. The exact place of lamotrigine, which controls some myoclonia and makes them worse in other patients, requires further study. The findings are clearer when specific syndromes are considered. Valproate is the treatment of first choice for benign myoclonic epilepsy in infants, myoclonic astatic epilepsy, epilepsy with myoclonic absences, eyelid myoclonia with absences, juvenile myoclonic epilepsy and progressive myoclonus epilepsy. The addition of ethosuximide to valproate can be helpful to those with myoclonic absences, where this combination appears more beneficial than either valproate or ethosuximide alone and in eyelid myoclonia with absences. Lamotrigine can be effective therapy for juvenile myoclonic epilepsy and eyelid myoclonia with absences when used alone and, in conjunction with other antiepileptic drugs (AED) (usually valproate) for early myoclonic encephalopathy, myoclonic-astatic epilepsy and particularly, epilepsy with myoclonic absences. The myoclonia of infantile neuronal ceroid lipofuscinosis respond to lamotrigine. Severe myoclonic epilepsy of infants usually worsens with lamotrigine, but occasionally, children improve. Zonisamide added to clonazepam and valproate or a barbiturate, can reduce the cascade of myoclonia in progressive myoclonus epilepsies for at least 2 years, but relapse may occur thereafter.
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PMID:Myoclonus and epilepsy in childhood: a review of treatment with valproate, ethosuximide, lamotrigine and zonisamide. 947 47

Within the last years five new antiepileptics have become available in Germany. Vigabatrin is a second choice drug against partial seizures, West syndrome and epilepsies in infant encephalopathy syndromes. Lamotrigine and Gabapentin can be used as add-on therapy in partial seizures in children above 12 years of age Felbamate has a high incidence of severe side-effects like aplastic anemia and liver failure. Therefore it should be restricted to the treatment of Lennox-Gastaut syndrome. Oxcarbazepine is not yet on the German market, but is available by import from Austria. Its therapeutic range is similar to carbamazepine with less side-effects. The new antiepileptics discussed have turned out to be useful additional therapeutics, especially in focal epilepsies. There is, however, still limited experience with these drugs in children. So none can as yet be considered a drug of first choice in any epileptic childhood disorder. The classical antiepileptic drugs remain essential in antiepileptic therapy.
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PMID:[Value of the new anticonvulsants in pediatrics]. 952 99

Lamotrigine (LTG), a newly introduced antiepileptic drug, appears to have potential therapeutic advantages for the treatment of patients with partial-onset seizures. Increasing clinical application and research of LTG demand a simpler and more rapid analytical procedure to determine LTG concentration in body fluids and tissues. The authors have developed an effective one-step procedure for sample preparation followed by high-performance liquid chromatography (HPLC) to quantitate LTG in plasma, urine, and brain tissues. Body fluids and brain homogenates were treated with cold acetonitrile to precipitate protein. The samples were fractionated on a 250 x 4.6 mm C18 reversed-phase column with an isocratic mobile system consisting of potassium phosphate buffer, acetonitrile, and methanol (70:16:14). The method had a LTG detection limit of 0.02 microg/ml in plasma and 0.03 microg/ml in urine. The coefficients of variation were <2.7% for intraday and 4.2% for interday analyses. The recovery of LTG added to plasma, urine, and brain homogenate ranged from 98% to 100%. The method was applied to a clinical study to determine plasma and urine concentrations of LTG in subjects receiving a single oral dose of LTG. The calculated pharmacokinetic parameters were comparable to those previously reported. The method proved to be simple, fast, reproducible, and useful in clinical investigation and monitoring of LTG concentrations.
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PMID:Determination of lamotrigine in biologic materials by a simple and rapid liquid chromatographic method. 955 36

This open pilot study was performed to evaluate the effect of Lamotrigine (LTG) in girls with Rett syndrome (RS) regarding seizure frequency, effect on gross motor dyspraxia and safety. Twelve girls with either the classical form of RS or the milder form fruste variants were included. The effect on epilepsy was evaluated as seizure frequency, motor performance (video comparison) and safety at clinical check up. The dosage of LTG was individualized and related to concomitant anti-epileptic drugs. Two of three girls with epilepsy responded relatively well to treatment, and for one of them even bad tantrums disappeared. LTG was useful in another four girls who became happier, more alert, more able to concentrate, and improved in contacting. Only mild adverse reactions as rash and tremor were seen. It is concluded that LTG could be worth trying as an adjunct in girls with RS, being aware of possible adverse reactions and no effect at all.
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PMID:Lamotrigine in Rett syndrome: treatment experience from a pilot study. 956 14

The clinical response to lamotrigine has been evaluated in a group of 63 drug resistant epileptic children in an open add-on trial. A negative response was observed in 30 subjects. In 11 patients, after an initial improvement lasting a mean period of 8 months, seizures recurred with the same frequency present before the beginning of the treatment. Twenty-two patients responded to lamotrigine treatment. Period of observation in the responsive group ranged from 1 year to 3 years. Response was complete in 16 patients and in the other 6 a 50% to 90% decrease of seizures was obtained. A complete normalization of the electroencephalogram (EEG) was registered in 10 cases after a mean period of 5 months of therapy. Side effects were mild and limited to 12 patients. Improvement was obtained in social and academic performance. Writing ability improved in one case. Lamotrigine can be considered a useful drug in the therapeutic armamentarium for childhood drug resistant epilepsy.
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PMID:Lamotrigine treatment in childhood drug resistant epilepsy. 956 59

A number of clinical trials that test the efficacy and safety of the newer antiepileptic drugs (AEDs) have recently been concluded. Two dose-response trials in inpatients with refractory partial seizures and outpatients with newly diagnosed partial epilepsy established the efficacy of gabapentin as monotherapy. Lamotrigine was found to have efficacy similar to that of phenytoin and carbamazepine (CBZ) and to be better tolerated than CBZ in patients with newly diagnosed epilepsy. It was also shown to have efficacy as monotherapy in partial seizures, based on the results of an active controlled trial, and in the treatment of absence seizures, based on the results of a responder-enriched study. Topiramate as monotherapy was found to be efficacious for treatment of partial-onset seizures, based on the results of a single-center dose-response trial. A dose-response trial that tested the efficacy of tiagabine monotherapy in patients with refractory partial epilepsy was uninformative. Oxcarbazepine was found to be safe and efficacious in four comparative trials in patients with newly diagnosed epilepsy as well as in one placebo-controlled inpatient trial in patients with refractory partial seizures.
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PMID:Monotherapy trials of new antiepileptic drugs. 957 42

An attempt is presented to use Lamictal (lamotrigine) produced by GlaxoWellcome in 30 patients with primary generalized epilepsy, already taking one of antiepileptic drugs, but refractory to this treatment. The patients were treated with carbamazepine (Amizepin) 600-1200 mg daily or with sodium valproate (Depakine) 1200-1600 mg daily. In the course of add-on therapy patients were receiving in first 4 weeks increasing doses of Lamictal starting from 50 mg or 25 mg (patients treated with sodium valproate). Maintenance dose of lamotrigine was 200 mg daily in two divided doses. The results of first three months of the treatment were generally positive. Half the patients experienced a reduction in seizure count by more than a half, what testify the Lamictal is a valuable medication in the treatment of primary generalized epilepsy. The observed side effects had transitory character.
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PMID:[Combined therapy with lamotrigine++ in primary generalized epilepsy in adult patients]. 963 75

The aim of the study was to evaluate the efficacy of lamotrigine (LTG, Lamictal) in patients with long-lasting epilepsy. The group of 11 patients, 4F, 7M aged 16-45 years, mean 31.3 years was included in the study. Complex partial seizures and complex partial with sec. generalization ones occurred in 5 patients, only simple and complex partial seizures in 4 and in 2 cases we observed primary generalized nonconvulsive seizures. The mean seizure frequency was 20/month before LTG treatment. The mean duration of epilepsy was 20 years. Monotherapy with carbamazepine was used in 2 patients, 9 took 2 antiepileptic drugs. The time of investigation and treatment was 4 months with 3 control visits. During LTG treatment the number of conventional antiepileptic drugs was reduced in 7 patients. The dose of the basic antiepileptic drug was not changed. We evaluated how LTG had influenced the frequency, severity and duration of seizures, patients' mental state and adverse events appearance. Good result of treatment--seizure frequency reduction at least 50%--was observed in 5 patients (45.5%), moderate--seizure frequency reduction below 50%--in 1 patient (9%), bad result--no change in seizure frequency or its increase--in 5 cases (45.5%). In 5 patients the drug influenced positively seizure severity and duration. Beneficial psychotropic effect of the drug was found in 2 patients with mental disturbances. Adverse effects occurred in 3 patients. They were vertigo and ataxia in 1 patient, drowsiness in 1 case and dyspeptic symptoms in 1 patient. Adverse events were mild and transient in 2 patients. In 1 patient with vertigo and ataxia they resulted in the drug being discontinued after 3 month treatment. On the whole lamotrigine shows a positive influence on the frequency, severity and duration of seizures in some patients with therapy resistant epilepsy. The drug is well tolerated and seems to have positive psychotropic effects.
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PMID:[The assessment of lamotrigine effectiveness in patients with drug-resistant epilepsy]. 976 May 48

Kainic acid-induced multifocal status epilepticus in the rat is a model of medically intractable complex partial seizures and neurotoxicity. The exact mechanisms of kainic acid epileptogenic and neurotoxic effects are unknown, but enhanced glutamate release seems to be an important factor. PNU-151774E ((S)-(+)-2-(4-(3-fluorobenzyloxy) benzylamino) propanamide, methanesulfonate) is a broad-spectrum new anticonvulsant with Na+ channel-blocking and glutamate release inhibiting properties. We have examined the effect of pretreatment with this compound on both seizure activity and hippocampal neuronal damage induced by systemic injection of kainic acid in rats. Lamotrigine, a recently developed anticonvulsant with similar glutamate release inhibitory properties, was tested for comparison, together with diazepam as reference standard, on the basis of its anticonvulsant and neuroprotectant properties in this animal model. PNU-151774E, lamotrigine (10, 30 mg/kg; i.p.) and diazepam (20 mg/kg; i.p.) were administered 15 min before kainic acid (10 mg/kg; i.p.). In the vehicle-treated group, kainic acid injection caused status epilepticus in 86% of animals. Hippocampal neuronal cell loss was 66% in the CA4 hippocampal area at 7 days after kainic acid administration. Diazepam inhibited both seizures and neurotoxicity. Lamotrigine reduced hippocampal neuronal cell loss at both doses, even when it did not protect from seizures, although it showed a trend toward protection. On the other hand PNU-151774E protected from both hippocampal neurodegeneration and status epilepticus. Thus, these data support the concept that seizure prevention and neuroprotection might not be tightly coupled. Glutamate release inhibition may play a major role in neuroprotection, but an additional mechanism(s) of action might be relevant for the anticonvulsant activity of PNU-151774E in this model.
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PMID:PNU-151774E protects against kainate-induced status epilepticus and hippocampal lesions in the rat. 983 Dec 89


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