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  • Title: Lamotrigine--a novel approach.
    Author: Meldrum BS.
    Journal: Seizure; 1994 Dec; 3 Suppl A():41-5. PubMed ID: 7894851.
    Abstract:
    Lamotrigine is an anticonvulsant chemically related to the antifolate compound pyrimidine. In the maximal electroshock test in rodents it is more potent and has a longer duration of action than other anticonvulsants, and it exhibits little acute neurotoxicity. Lamotrigine suppresses sustained repetitive firing by prolonging inactivation of the sodium channel in the neuronal membrane. It blocks the pathological, but not the normal, release of glutamate and aspartate. Lamotrigine is also cerebroprotective in rodent models of stroke or focal ischaemia. This effect correlates with the suppression of glutamate release and is probably due principally to the action on sodium channels. Lamotrigine has a favourable pharmacokinetic profile. It is rapidly and completely absorbed and has linear pharmacokinetics. Protein binding is moderate and, as lamotrigine does not induce liver enzymes, it does not alter the pharmacokinetics of other anticonvulsants. The half-life and clearance of lamotrigine are altered by concomitant antiepileptic therapy. In the presence of the enzyme inhibitor sodium valproate the half-life is doubled and this interaction is clinically significant.
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