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

Fifty-two children with intractable epilepsy received lamotrigine as add-on therapy on a compassionate basis. The results were reviewed after three and six months of treatment in order to evaluate the efficacy in different epilepsy syndromes. Mental retardation was present in 60% of the children. Ictal EEG was obtained in 38 children. At three months the median monthly seizure frequency was reduced from 46 to 14 in the 37 children that still received lamotrigine (p < 0.01). Seven children were seizure-free. Seizure reduction was most impressive in generalized epilepsy, since 63% of these had more than 50% seizure reduction compared to 18% in partial epilepsies (p < 0.05). This difference was unchanged after six months of treatment. Side effects were reported in 18 of the children. In 13 children the parents reported an improved wellbeing. Lamotrigine seems to be an efficient antiepileptic drug-especially in generalized epilepsy.
 ...
PMID:[Treatment of childhood epilepsy with lamotrigine. An evaluation of efficacy in different types of epilepsy]. 865 Jul 72

Lamotrigine [0.5-10 mg/kg, intraperitoneally (i.p.)] was able to antagonize the audiogenic seizures in DBA/2 mice in a dose-dependent manner. Lamotrigine at doses of 0.5 and 1.25 mg/kg i.p., which per se did not significantly affect the occurrence of audiogenic seizures in DBA/2 mice, markedly potentiated the anticonvulsant activity of carbamazepine, diazepam, phenytoin, phenobarbital and valproate against sound induced seizures in DBA/2 mice. The degree of potentiation by lamotrigine was greatest for diazepam and valproate, lower for phenobarbital, and least for phenytoin and carbamazepine. The increase in anticonvulsant activity was associated with a comparable increase in motor impairment. However, the therapeutic index of combined treatment of diazepam + lamotrigine or valproate + lamotrigine was more favourable than the diazepam + saline or valproate + saline treatment. Since lamotrigine did not significantly influence the plasma levels of the anticonvulsant drugs studied we might suggest that pharmacokinetic interactions, in terms of total plasma levels, are not probable. However, the possibility that lamotrigine alters protein binding and increases the relative free vs protein bound ratio may not be excluded. Lamotrigine did not significantly affect the hypothermic effects of the anticonvulsant compounds studied. Lamotrigine showed an additive effect when administered in combination with some classical anticonvulsants, most notably valproate and diazepam.
 ...
PMID:Lamotrigine potentiates the antiseizure activity of some anticonvulsants in DBA/2 mice. 873 83

In drug-resistant epilepsy the use of VGB, LTG, oxcarbazepine, FBM and GBP resulted in at least a 50% improvement in 20% to 60% of such patients treated and in 7% led to complete seizure control. In the long term, VGB may lose its efficacy and give rise to tolerance phenomena. Another frequent disadvantage of VGB is poor compliance owing to the large number of tablets needed to achieve the necessary dose (2-3 g). VGB may also induce a worsening of myoclonic epilepsies and seems ineffective in absences; whereas it can induce a good response in West's syndrome. LTG and FBM yielded a good response in idiopathic generalized epilepsies and were effective in refractory partial seizures, West's syndrome and Lennox-Gastaut's syndrome. After being suspended because of the risks of bone-marrow aplasia and liver toxicity, FBM trials began again in 1995, use of the drug being restrict to drug-resistant partial epilepsies and to Lennox-Gastaut's syndrome. Oxcarbazepine has an efficacy equal to that of CBZ, but had fewer side effects and very few interactions with other drugs. Although GBP has few side effects and acts as an anticonvulsant in subjects with resistant partial epilepsy, some reports suggest that it can lose its efficacy around the 18th or 19th month.
 ...
PMID:[New antiepileptic drugs: a review and personal contribution]. 876 54

Lamotrigine (LTG) is a novel antiepileptic drug (AED) with a spectrum of activity in animal models of epilepsy similar to that of phenytoin and carbamazepine. In some models it appears to have a broader spectrum and better tolerability than these agents, however. One mechanism of action of LTG is the marked inhibition of release of the excitatory neurotransmitters glutamate and aspartate under conditions of sustained repetitive firing. LTG appears to do this by blocking voltage-sensitive sodium channels and has no direct effect on N-methyl-D-aspartate (NMDA) receptors. In clinical trials as add-on therapy in medically refractory partial seizure patients, LTG has consistently produced a 50% reduction in seizure frequency in 25-34% of subjects. LTG is well tolerated, even in the add-on situation. In part, this appears to be related to positive behavioral effects. Desirable pharmacologic properties of LTG include low protein binding (55%), an absence of enzyme induction, and linear pharmacokinetics. The most significant adverse effect is rash, leading to a withdrawal rate of 2% of patient exposures in clinical trials.
 ...
PMID:Lamotrigine. 878 17

Lamotrigine (LTG) was used in 12 patients with juvenile myoclonic epilepsy (JME) who either had sodium valproate (VPA) side effects or did not wish to take VPA. Five patients are now fully controlled on LTG monotherapy. Side-effects were corrected by VPA withdrawal or reduction except for severe weight gain. In three patients it was not possible to withdraw VPA due to the re-emergence of myoclonus, suggesting LTG-VPA synergism. Two patients had successful pregnancies whilst taking LTG. Lamotrigine is a useful alternative in the management of JME.
Seizure 1996 Jun
PMID:The use of lamotrigine in juvenile myoclonic epilepsy. 879 32

The newly introduced antiepileptic drug, lamotrigine, has been reported to have a mechanism of action similar to that of phenytoin. Because phenytoin is a standard clinical treatment for convulsive status epilepticus, we compared the efficacy of lamotrigine to that of phenytoin in a model of secondarily generalized convulsive status epilepticus in rats that responds to drug concentrations similar to those that have been reported to be clinically useful for this purpose. Status epilepticus was induced in rats with actively epileptogenic cortical cobalt lesions by administration of homocysteine thiolactone. While phenytoin-controlled generalized tonic clonic seizures in this model with a median effective dose of 100.5 mg/kg (16.0 micrograms/ml in serum), lamotrigine was ineffective at doses ranging from 10 to 100 mg/kg, with serum drug concentrations (2.5-43.5 micrograms/ml) within or above the reported 'therapeutic' concentration for LTG treatment of chronic epilepsy. Lamotrigine also failed to prevent the onset of generalized tonic clonic seizures when given prior to homocysteine, while phenytoin was effective in this test. Studies of lamotrigine kinetics in serum and brain revealed that the drug was well-absorbed following i.p. injection and that it entered brain rapidly enough to have exerted an anti-status effect in these experiments. These results suggest that lamotrigine and phenytoin have differences in their mechanisms of anticonvulsant action, leading to very different abilities to control status epilepticus.
 ...
PMID:Lamotrigine vs. phenytoin for treatment of status epilepticus: comparison in an experimental model. 880 Jun 32

In pyramidal cortical cells, high-voltage-activated Ca2+ currents affect seizure propagation and the release of excitatory amino acids at the corticostriatal axon terminals. The new antiepileptic drug lamotrigine (Lamictal) produced a large and dose-dependent inhibition of high-voltage-activated Ca2+ currents (IC50 = 12.3 microM) in rat cortical neurons. This action was not blocked by the dihydropyridine receptor antagonist nifedipine; instead, the response was blocked by the concomitant application of the N-type Ca2+ channel blocker, omega-conotoxin GVIA (1-3 microM) and the P-type Ca2+ channel blocker, omega-agatoxin-IVA (20-100 nM). These findings demonstrate that lamotrigine, at therapeutic doses, is capable of modulating the Ca2+ conductances involved in excitatory amino acid release in the corticostriatal pathway, partially explaining lamotrigine usefulness in the therapy of epilepsy as well as in the treatment of excitatory amino acid-induced neurotoxicity.
 ...
PMID:Lamotrigine inhibits Ca2+ currents in cortical neurons: functional implications. 883 Nov 12

This open, clinical study describes the use of lamotrigine in 200 adults and children with drug resistant epilepsy. Lamotrigine was used largely as add-on therapy and outcome was assessed by the patients, parents and carers and the physician in terms of reduction of seizure frequency, drug side-effects and improvement in quality of life. Of the 200 patients, 70 (35%) were rendered seizure free. Lamotrigine was especially helpful in resistant primary generalized epilepsy, complex partial seizures, mixed seizures subsequent to brain damage, Lennox-Gastaut syndrome and in complex partial seizures which secondarily generalized. Fifty-three patients ceased lamotrigine; 30 due to lack of effect, and 13 due to side-effects. Lamotrigine is a very useful antiepileptic medication of a "broad spectrum' nature being effective in primary generalized epilepsy and partial seizures as add-on therapy. The side-effect profile is good with most side-effects being avoidable.
Seizure 1996 Sep
PMID:Lamotrigine: clinical experience in 200 patients with epilepsy with follow-up to four years. 890 23

Lamotrigine (LAG) is a new antiepileptic drug which is licensed as adjunctive therapy for partial and secondary generalized seizures. In the present study, the mechanisms responsible for its antiepileptic effect were studied in rat amygdaloid slices using intracellular recording and whole-cell patch clamp techniques. Bath application of LAG (50 microM) reversibly suppressed the excitatory postsynaptic potentials (EPSPs) and currents (EPSCs) evoked by stimulating ventral endopyriform nucleus. Synaptic response mediated by the N-methyl-D-aspartate (NMDA) receptor (EPSPNMDA) was isolated pharmacologically by application of a solution containing non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX,10 microM) and gamma-aminobutyric acidA receptor antagonist bicuculline (20 microM). LAG produced a parallel inhibition of EPSPNMDA. Postsynaptic depolarization induced by alpha-amino-5-methyl-4-isoxazole propionate (AMPA) was not altered by LAG. In addition, LAG increased the ratio of the second pulse response to the first pulse response (P2/P1), which is consistent with a presynaptic mode of action. The L-type Ca+2 channel blocker nifedipine (20 microM) had no effect on LAG-induced presynaptic inhibition. However, the depressant effect of LAG was markedly reduced in slices pretreated with N-type Ca+2 channel blocker omega-conotoxin-GVIA (omega-CgTX-GVIA, 1 microM) or a broad spectrum Ca+2 channel blocker omega-conotoxin-MVIIC (omega-CgTX-MVIIC, 1 microM). It is concluded that a reduction in omega-CgTX-GVIA-sensitive Ca+2 currents largely contributes to LAG-induced presynaptic inhibition.
 ...
PMID:Presynaptic inhibition of excitatory neurotransmission by lamotrigine in the rat amygdalar neurons. 892 65

The antiepileptic effect of lamotrigine (Lamictal) was assessed in a double-blind, placebo-controlled, crossover trial in 56 adult patients with refractory partial seizures. Lamotrigine or placebo was added to the patients' existing antiepileptic drugs (AEDs). The dose of lamotrigine varied from 75 to 400 mg daily. Thirty-eight patients completed the trial and 7 withdrew because of adverse experiences. There was a statistically significant reduction in seizure counts on lamotrigine compared with placebo for total seizures (30.3% reduction, 95% CI 8.4%, 47.0%), complex partial seizures (29.2% reduction, 95% CI 3.8%, 47.9%) and secondary generalised seizures (37.9%, CI 18.9%, 52.4%). The analysis of total seizure days showed a similar significant reduction during lamotrigine treatment for the same seizure categories. There was no statistically significant difference in reporting of adverse events between lamotrigine and placebo except for dizziness which was reported more frequently on lamotrigine than on placebo. There were no differences in abnormal haematological or biochemical findings between lamotrigine and placebo, and lamotrigine had no effect on plasma concentrations of concomitant AEDs.
 ...
PMID:Controlled trial of lamotrigine (Lamictal) for treatment-resistant partial seizures. 893 35


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>