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    Several electrophysiological studies have investigated the effects of lamotrigine on voltage-dependent sodium channels.


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    For example, lamotrigine blocked sustained repetitive firing in cultured mouse spinal cord neurons in a concentration-dependent manner, at concentrations that are therapeutically relevant in the treatment of human seizures.

    In cultured hippocampal neurons, lamotrigine reduced sodium currents in a voltage-dependent manner, and at depolarised potentials showed a small frequency-dependent inhibition.

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    These and a variety of other results indicate that the antiepileptic effect of lamotrigine, like those of phenytoin and carbamazepine, is at least in part due to use- and voltage-dependent modulation of fast voltage-dependent sodium currents.

    However, lamotrigine has a broader clinical spectrum of activity than phenytoin and carbamazepine and is recognised to be protective against generalised absence epilepsy and other generalised epilepsy syndromes, including primary generalised tonic—clonic seizures, juvenile myoclonic epilepsy, and Lennox-Gastaut syndrome.

    The basis for this broader spectrum of activity of lamotrigine is unknown, but could relate to actions of the drug on voltage-activated calcium channels.

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    Lamotrigine blocks T-type calcium channels weakly, if at all. Whether this activity on calcium channels accounts for lamotrigine's broader clinical spectrum of activity in comparison with phenytoin and carbamazepine remains to be determined.


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    Available data indicate that its bioavailability is not affected by food. This is independent of dose and is similar following single and multiple doses in both patients with epilepsy and in healthy volunteers.

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