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)

Lamotrigine (LTG), 6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine, is a novel antiepieptic drug structurally unrelated to the major anticonvulsants in current use. Previous studies of LTG in rodents revealed efficacy in maximal electroshock test, pentylenetetrazol test and kindling models of seizures suggesting potential utility in the treatment of partial and generalized (tonic-clonic) seizures. In the present study, LTG was found to block sustained repetitive firing of sodium-dependent action potentials in mouse spinal cord cultured neurons and inhibit [3H]batrachotoxinin A 20-alpha-benzoate binding in rat brain synaptosomes suggesting a direct interaction with voltage-activated sodium channels.
 ...
PMID:An in vitro investigation of the action of lamotrigine on neuronal voltage-activated sodium channels. 133 55

We report our experience with lamotrigine add-on therapy in the treatment of 11 patients with Lennox-Gastaut syndrome. Lamotrigine is a novel antiepileptic drug, chemically unrelated to the major anticonvulsants in current use. Ten patients experienced a > 50% reduction in seizure frequency, 1 patient experienced no change in seizure frequency. All patients tolerated lamotrigine satisfactorily and no side-effects were reported.
 ...
PMID:Lamotrigine as an add-on drug in the management of Lennox-Gastaut syndrome. 149 Apr 94

Lamotrigine (LTG), a new anticonvulsant, chemically unrelated to current antiepileptic drugs (AEDs), resembles phenytoin (PHT) and carbamazepine (CBZ) in ability to block hindlimb extension in both the maximal electroshock test and leptazol-induced seizures. Results indicate that LTG may be of value in both partial and generalized seizures. In in vitro studies, LTG has been shown to inhibit veratrine-evoked release of glutamate when a threshold depolarizing concentration (4 micrograms/ml) is used, and also inhibits aspartate release when a larger stimulus is given (10 micrograms/ml). However, LTG does not block potassium-evoked transmitter release. LTG is a less potent inhibitor of the release of gamma-aminobutyric acid (GABA), acetylcholine, noradrenaline, and dopamine. LTG blocks the neurotoxicity of kainic acid in vivo, supporting the in vitro findings, and suggests that the anticonvulsant effect of LTG may be due to inhibition of glutamate release. In a test of working memory and phencyclidine (PCP) discrimination studies, LTG had no effect, indicating no sharing of the same PCP-like side effects associated with NMDA receptor blockade. In the gerbil model of global ischemia, high doses of LTG provided protection against damage to the CA1 region of the hippocampus. Analogues of LTG of higher potency to block the release of glutamate may be necessary to ensure protection against ischemic brain damage.
 ...
PMID:Neurochemical and behavioral aspects of lamotrigine. 168 39

For the majority of human epilepsy syndromes, the molecular and cellular basis for the epileptic activity remains largely conjectural. The principal hypotheses currently concern: defects in membrane ionic conductances or transport mechanisms; defects in gamma-aminobutyric acid (GABA)-mediated inhibitory processes; and enhanced or abnormal excitatory synaptic action. Substantial evidence exists in humans and animals for acquired abnormalities in excitatory amino acid neurotransmission that may participate in the abnormal patterns of neuronal discharge, and this could provide the morphological basis for a recurrent excitatory pathway sustaining seizure discharges in temporal lobe epilepsy. In practice, two approaches appear significant in the suppression of seizures. One is to act postsynaptically on receptors to decrease the excitation induced by glutamate, and the other is to decrease synaptic release of glutamate and aspartate. Agents acting upon adenosine or GABAB receptors decrease glutamate release in vitro but do not have significant anticonvulsant activity, probably because of their predominant actions at other sites. Lamotrigine blocks stimulated release of glutamate and shows anticonvulsant activity in a wide range of animal models.
 ...
PMID:Excitatory amino acid transmitters in epilepsy. 172 42

Lamotrigine (LTG), 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine, is a structurally novel anticonvulsant. The anticonvulsant profile of LTG following oral administration in two standard anticonvulsant tests, the maximal electroshock (MES) test in mice and rats and the pentylenetetrazol (PTZ) infusion test in mice, was studied in comparison with the known anticonvulsant drugs phenytoin (PHT), phenobarbitone, diazepam, carbamazepine (CBZ), sodium valproate, ethosuximide (ETH), and troxidone (TROX). ED50 values for the abolition of hindlimb extension (HLE) in the MES test and PTZ infusion tests and doses increasing the latency of PTZ-evoked clonus were determined. The duration of action of LTG was examined in rats and mice in the MES test by determining ED50 values for the abolition of HLE at various drug intervals to shock administration. In the MES test, LTG was well absorbed in both species, with peak activity at 1 h and persistence at this level of potency for at least 8 h. Of the drugs examined, LTG was ranked the most potent and persistent in both species. LTG also abolished PTZ-evoked HLE, while ETH and TROX were inactive. Clonus latency was not increased by LTG, PHT, or CBZ, but was significantly increased (p less than 0.05) by the remaining anticonvulsants. Thus, LTG resembled PHT and CBZ in its ability to block HLE but not to increase PTZ-induced clonus latency. Acute behavioural studies in mice and rats have suggested a wide separation between anticonvulsant doses and those producing behavioural impairment. These results suggest that LTG may be of value in the treatment of generalised tonic-clonic and partial seizures.
 ...
PMID:Pharmacological studies on lamotrigine, a novel potential antiepileptic drug: I. Anticonvulsant profile in mice and rats. 375 35

There are several new antiepileptic drugs undergoing extensive clinical investigation. Five new drugs--vigabatrin, lamotrigine, gabapentin, felbamate and oxcarbazepine--appear to be the most widely tested and promising agents. Vigabatrin is most effective in drug-resistant partial epilepsy. Vigabatrin is also effective in infantile spasms, but seems to have negative effects on myoclonic epilepsies and absence seizures. Lamotrigine and felbamate seem to be effective in partial epilepsy and in Lennox-Gastaut syndrome. In addition, lamotrigine and felbamate seem to have efficacy in idiopathic generalised epilepsies. Oxcarbazepine appears to be equally as effective as carbamazepine, but less toxic. Gabapentin has few adverse effects and has efficacy in some patients with drug-resistant partial epilepsy. Some of the new antiepileptic drugs modify excitatory or inhibitory amino acid transmission, but some of them may employ new, still unknown mechanisms of action. Depending on the mechanism of action, the therapeutic effectiveness of the antiepileptic drugs may differ in specific epileptic syndromes. Future antiepileptic drugs may thus give us the possibility to design rational polypharmacy for individual patients by combining agents with different spectra of effectiveness. Considering the goal of good tolerability in the development of the new antiepileptic drugs, polypharmacy with these agents is not expected to increase adverse effects significantly.
 ...
PMID:Place of newer antiepileptic drugs in the treatment of epilepsy. 751 Jun 9

Lamictal (Lamotrigin) action was studied in 61 patients with partial and generalized epileptic seizures (not fewer than twice a month). Most of the patients received Lamictal in doses of 200-300 mg daily as well as other antiepileptic medications (before lamictal all patients were treated without effect with various antiepileptic medications). Effectiveness of treatment with lamictal includes: the cessation of epileptic attacks (5 patients), its more rare appearance (31 patients), transformation into more light fits (15 patients). Lamictal has a broad spectrum of antiepileptic activity: it stops generalized tonic-clonic seizures, absences, simple and complex partial seizures as well as secondarily generalized tonic-clonic seizures. The medication is also effective in patients with psychopathologic symptoms.
 ...
PMID:[Lamiktal in the treatment of epilepsy patients]. 757 23

This open study reports the use of lamotrigine in 93 adults and children with drug resistant epilepsy. Lamotrigine was used predominantly as add-on therapy and outcome was assessed by the patient, parents and carers and the physician in terms of reduction of seizure frequency, drug side effects, and importantly with this drug, improvement in quality of life. Twenty five of the 93 patients (26.9%) studied were rendered seizure free with the addition of lamotrigine to their therapy. This was especially the case for patients with complex partial seizures, generalised seizures secondary to brain damage, primary generalised epilepsy and the Lennox Gastaut syndrome. Quality of life improvements were especially striking in patients with seizures secondary to brain damage and in the Lennox Gastaut Syndrome. Twenty eight patients ceased lamotrigine, 13 due to lack of effect and the remainder due to side effects. Lamotrigine is a potentially very useful anti-epileptic medication in persons with complex partial seizures, but also in primary generalised epilepsy, the Lennox Gastaut syndrome and especially in those individuals who have seizures subsequent to brain damage.
 ...
PMID:Lamotrigine: clinical experience in 93 patients with epilepsy. 757 57

The severe epilepsies of childhood are described briefly and information available on the efficacy of newly developed antiepileptic drugs (AEDs) in their control is reviewed. Therapeutic advances are awaited for early infantile epileptic encephalopathy, early myoclonic encephalopathy, progressive myoclonus epilepsies and Kojewnikow syndrome. West syndrome may respond to vigabatrin, and less predictably to lamotrigine. Lamotrigine can be helpful for severe myoclonic epilepsy and myoclonic absences. Astatic seizures may be dramatically controlled by lamotrigine, whereas vigabatrin may worsen myoclonic attacks. In the Lennox-Gastaut syndrome, the efficacy of felbamate has been demonstrated by a controlled trial; vigabatrin and lamotrigine can also be helpful. Non-idiopathic partial and secondary generalized epilepsies are responsive to vigabatrin in a useful percentage of cases, and some children improve with felbamate, lamotrigine or striripentol. A trial which compares the efficacies of the newer AEDs against each other could provide very useful information for the clinician.
Seizure 1995 Sep
PMID:Management issues in severe childhood epilepsies. 758 57

Lamotrigine (LTG) has recently been approved for marketing in Australia as add-on therapy in resistant partial seizure disorders. Early reports cited a therapeutic blood level for LTG of 1-3 mg/L (4-12 mumol/L). Aspects of routine patient care with LTG, devoid of the restrictions of trial protocols, are discussed. Forty-five patients commenced therapy but 15 discontinued LTG. Of the remaining 30 patients, 9 became seizure free, 3 from the de novo trial in focal epilepsy and 6 with generalised epilepsy. Global evaluation of patients showed mild to moderate improvement for those with focal epilepsy and moderate to marked improvement for those with generalised epilepsy. Blood levels of LTG did not provide clinically useful information.
 ...
PMID:Routine use of lamotrigine, a new anti-epileptic medication, and the value of measuring its blood levels. 758 66


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