Historical note and terminology
The era of antiepileptic drugs started with the introduction of bromides in 1857. It was followed by the discovery of the anticonvulsant effect of barbiturates in 1912 and the introduction of hydantoins in 1916. Carbamazepine was introduced into clinical practice as an antiepileptic drug in 1963. Carbamazepine as well as lamotrigine blocks the repetitive firing of neurons by blocking sodium channels. Unrelated to any previous antiepileptic drug, lamotrigine reduces presynaptic excitatory amino acid release. Like most other antiepileptic drugs, the discovery of lamotrigine was serendipitous. Its discovery was based on the suggestion that the antiepileptic effect of phenytoin and phenobarbital is due to the disturbances of folate metabolism caused by these drugs (Reynolds et al 1966). This led to an investigation of several folate antagonists in animal models, including phenyltriazines with strong antiepileptic action, even though the antifolate action was mild. Lamotrigine was developed from this category of compounds for treatment of partial seizures in 1995. It is approved worldwide.
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